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    Does moderate hypothermia really carry less bleeding risk than deep hypothermia for circulatory arrest? A propensity-matched comparison in hemiarch replacement. Keenan Jeffrey E,Wang Hanghang,Gulack Brian C,Ganapathi Asvin M,Andersen Nicholas D,Englum Brian R,Krishnamurthy Yamini,Levy Jerrold H,Welsby Ian J,Hughes G Chad The Journal of thoracic and cardiovascular surgery BACKGROUND:Moderate (MHCA) versus deep (DHCA) hypothermia for circulatory arrest in aortic arch surgery has been purported to reduce coagulopathy and bleeding complications, although there are limited data supporting this claim. This study aimed to compare bleeding-related events after aortic hemiarch replacement with MHCA versus DHCA. METHODS:Patients who underwent hemiarch replacement at a single institution from July 2005 to August 2014 were stratified into DHCA and MHCA groups (minimum systemic temperature ≤20°C and >20°C, respectively) and compared. Then, 1:1 propensity matching was performed to adjust for baseline differences. RESULTS:During the study period, 571 patients underwent hemiarch replacement: 401 (70.2%) with DHCA and 170 (29.8%) with MHCA. After propensity matching, 155 patients remained in each group. There were no significant differences between matched groups with regard to the proportion transfused with red blood cells, plasma, platelet concentrates, or cryoprecipitate on the operative day, the rate of reoperation for bleeding, or postoperative hematologic laboratory values. Among patients who received plasma, the median transfusion volume was statistically greater in the DHCA group (6 vs 5 units, P = .01). MHCA also resulted in a slight reduction in median volume of blood returned via cell saver (500 vs 472 mL, P < .01) and 12-hour postoperative chest tube output (440 vs 350, P < .01). Thirty-day mortality and morbidity did not differ significantly between groups. CONCLUSIONS:MHCA compared with DHCA during hermiarch replacement may slightly reduce perioperative blood-loss and plasma transfusion requirement, although these differences do not translate into reduced reoperation for bleeding or postoperative mortality and morbidity. 10.1016/j.jtcvs.2016.08.014
    The impact of temperature in aortic arch surgery patients receiving antegrade cerebral perfusion for >30 minutes: How relevant is it really? Preventza Ourania,Coselli Joseph S,Akvan Shahab,Kashyap Sarang A,Garcia Andrea,Simpson Katherine H,Price Matt D,Mayor Jessica,de la Cruz Kim I,Cornwell Lorraine D,Omer Shuab,Bakaeen Faisal G,Haywood-Watson Ricky J L,Rammou Athina The Journal of thoracic and cardiovascular surgery OBJECTIVE:We examined the early outcomes and the long-term survival associated with different degrees of hypothermia in patients who received antegrade cerebral perfusion (ACP) for >30 minutes. METHODS:During a 10-year period, 544 consecutive patients underwent proximal and total aortic arch surgery and received ACP for >30 minutes and 1 of 3 levels of hypothermia: deep (14.1°C-20°C; n = 116 [21.3%]), low-moderate (20.1°C-23.9°C; n = 262 [48.2%]), and high-moderate (24°C-28°C; n = 166 [30.5%]). A variable called "predicted temperature" was used in propensity-score analysis. Multivariate analysis was done to evaluate the effect of actual temperature on outcomes. RESULTS:The operative mortality rate was 12.5% (n = 68) overall and was 15.5%, 11.8%, and 11.5% in the deep, low-moderate, and high-moderate hypothermia patients, respectively (P = .54). The persistent stroke rate was 6.6% overall and 12.2%, 4.6%, and 6.0% in these 3 groups, respectively (P = .024 on univariate analysis). On multivariate analysis, actual temperature was not associated with mortality, but lower temperatures predicted persistent stroke and reoperation for bleeding. In the propensity-matched subgroups, the patients with predicted deep hypothermia had (nonsignificantly) greater rates of persistent stroke (12.2% vs 4.9%; relative risk, 1.08; 95% CI, 0.87-1.15) and reoperation for bleeding (14.6% vs 2.4%; relative risk, 1.14; 95% CI, 0.87-1.15) than the patients with predicted moderate hypothermia. On long-term follow-up (mean duration, 5.12 years), 4- and 8-year survival rates were 62.3% and 55.7% in the deep hypothermia group and 75.4% and 74.2% in the moderate hypothermia group (P = .0015). CONCLUSIONS:In proximal and arch operations involving ACP for >30 minutes, greater actual temperatures were associated with less stroke and reoperation for bleeding. There were no significant differences among the predicted hypothermia levels, although a trend toward a higher rate of adverse events was noticed in the deep hypothermia group. Long-term survival was better in the moderate hypothermia group. 10.1016/j.jtcvs.2016.11.059
    Neuroprotective Effects of Annexin A1 Tripeptide after Deep Hypothermic Circulatory Arrest in Rats. Zhang Zhiquan,Ma Qing,Shah Bijal,Mackensen G Burkhard,Lo Donald C,Mathew Joseph P,Podgoreanu Mihai V,Terrando Niccolò Frontiers in immunology Resolution agonists, including lipid mediators and peptides such as annexin A1 (ANXA1), are providing novel approaches to treat inflammatory conditions. Surgical trauma exerts a significant burden on the immune system that can affect and impair multiple organs. Perioperative cerebral injury after cardiac surgery is associated with significant adverse neurological outcomes such as delirium and postoperative cognitive dysfunction. Using a clinically relevant rat model of cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA), we tested the pro-resolving effects of a novel bioactive ANXA1 tripeptide (ANXA1sp) on neuroinflammation and cognition. Male rats underwent 2 h CPB with 1 h DHCA at 18°C, and received vehicle or ANXA1sp followed by timed reperfusion up to postoperative day 7. Immortalized murine microglial cell line BV2 were treated with vehicle or ANXA1sp and subjected to 2 h oxygen-glucose deprivation followed by timed reoxygenation. Microglial activation, cell death, neuroinflammation, and NF-κB activation were assessed in tissue samples and cell cultures. Rats exposed to CPB and DHCA had evident neuroinflammation in various brain areas. However, in ANXA1sp-treated rats, microglial activation and cell death (apoptosis and necrosis) were reduced at 24 h and 7 days after surgery. This was associated with a reduction in key pro-inflammatory cytokines due to inhibition of NF-κB activation in the brain and systemically. Treated rats also had improved neurologic scores and shorter latency in the Morris water maze. In BV2 cells treated with ANXA1sp, similar protective effects were observed including decreased pro-inflammatory cytokines and cell death. Notably, we also found increased expression of ANXA1, which binds to NF-κB p65 and thereby inhibits its transcriptional activity. Our findings provide evidence that treatment with a novel pro-resolving ANXA1 tripeptide is neuroprotective after cardiac surgery in rats by attenuating neuroinflammation and may prevent postoperative neurologic complications. 10.3389/fimmu.2017.01050
    Outcomes after thoracoabdominal aortic aneurysm repair using hypothermic circulatory arrest. Kouchoukos Nicholas T,Kulik Alexander,Castner Catherine F The Journal of thoracic and cardiovascular surgery OBJECTIVE:To evaluate our experience with thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass and hypothermic circulatory arrest. METHODS:A total of 243 patients underwent thoracoabdominal aortic aneurysm repair with full cardiopulmonary bypass and hypothermic circulatory arrest. The degree of repair was Crawford extent I in 63 (26%), Crawford extent II in 97 (40%), and Crawford extent III in 83 patients (34%). Degenerative aneurysms were the most frequent indication for surgery, and 18 patients (7.4%) required emergency surgery. RESULTS:The mean duration of cardiopulmonary bypass and hypothermic circulatory arrest was 160 ± 44 and 31 ± 12 minutes, respectively. Stroke occurred in 9 patients (3.7%) and spinal cord ischemic injury in 13 patients (5.3%; 9 with paraplegia and 4 with paraparesis). Temporary dialysis for new-onset renal failure was required in 3.6% of hospital survivors. The 30-day mortality rate was 7.8% (13 patients). It was 33.3% after emergency surgery and 5.6% after elective surgery (P = .001). Spinal cord ischemic injury occurred more frequently after emergency than after elective surgery (16.7% vs 3.9%; P = .04). The overall 5-year survival was 55% and was significantly better for patients with nondegenerative aortic disease. CONCLUSIONS:Cardiopulmonary bypass with hypothermic circulatory arrest can be safely used for thoracoabdominal aortic aneurysm repair, providing excellent protection against end-organ injury. The early and late mortality rates did not exceed those reported for other open techniques or for endovascular repair, with particularly favorable outcomes among patients undergoing elective repair. 10.1016/j.jtcvs.2012.11.077
    Does supply meet demand? A comparison of perfusion strategies on cerebral metabolism in a neonatal swine model. Mavroudis Constantine D,Ko Tiffany,Volk Lindsay E,Smood Benjamin,Morgan Ryan W,Lynch Jennifer M,Davarajan Mahima,Boorady Timothy W,Licht Daniel J,Gaynor J William,Mascio Christopher E,Kilbaugh Todd J The Journal of thoracic and cardiovascular surgery OBJECTIVE:We aimed to determine the effects of selective antegrade cerebral perfusion compared with other perfusion strategies on indices of cerebral blood flow, oxygenation, cellular stress, and mitochondrial function. METHODS:One-week-old piglets (n = 41) were assigned to 5 treatment groups. Thirty-eight were placed on cardiopulmonary bypass. Of these, 30 were cooled to 18°C and underwent deep hypothermic circulatory arrest (n = 10), underwent selective antegrade cerebral perfusion at 10 mL/kg/min (n = 10), or remained on continuous cardiopulmonary bypass (deep hypothermic cardiopulmonary bypass, n = 10) for 40 minutes. Other subjects remained on normothermic cardiopulmonary bypass (n = 8) or underwent sham surgery (n = 3). Novel, noninvasive optical measurements recorded cerebral blood flow, cerebral tissue oxyhemoglobin concentration, oxygen extraction fraction, total hemoglobin concentration, and cerebral metabolic rate of oxygen. Invasive measurements of cerebral microdialysis and cerebral blood flow were recorded. Cerebral mitochondrial respiration and reactive oxygen species generation were assessed after the piglets were killed. RESULTS:During hypothermia, deep hypothermic circulatory arrest piglets experienced increases in oxygen extraction fraction (P < .001), indicating inadequate matching of oxygen supply and demand. Deep hypothermic cardiopulmonary bypass had higher cerebral blood flow (P = .046), oxyhemoglobin concentration (P = .019), and total hemoglobin concentration (P = .070) than selective antegrade cerebral perfusion, indicating greater oxygen delivery. Deep hypothermic circulatory arrest demonstrated worse mitochondrial function (P < .05), increased reactive oxygen species generation (P < .01), and increased markers of cellular stress (P < .01). Reactive oxygen species generation was increased in deep hypothermic cardiopulmonary bypass compared with selective antegrade cerebral perfusion (P < .05), but without significant microdialysis evidence of cerebral cellular stress. CONCLUSIONS:Selective antegrade cerebral perfusion meets cerebral metabolic demand and mitigates cerebral mitochondrial reactive oxygen species generation. Excess oxygen delivery during deep hypothermia may have deleterious effects on cerebral mitochondria that may contribute to adverse neurologic outcomes. We describe noninvasive measurements that may help guide perfusion strategies. 10.1016/j.jtcvs.2020.12.005
    Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest. Kertai Miklos D,Cheruku Sreekanth,Qi Wenjing,Li Yi-Ju,Hughes G Chad,Mathew Joseph P,Karhausen Jörn A The Journal of thoracic and cardiovascular surgery OBJECTIVE:Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and proinflammatory effectors, we investigated their role in intraoperative hypotension. METHODS:We studied 31 patients undergoing proximal aortic repair with hypothermic circulatory arrest between June 2013 and April 2015 at Duke University Medical Center. Plasma samples were obtained at different intraoperative time points to quantify chymase, interleukin-6, interleukin-8, tumor necrosis factor alpha, and white blood cell CD11b expression. Hypotension was defined as the area (minutes × millimeters mercury) below a mean arterial pressure of 55 mm Hg. Biomarker responses and their association with intraoperative hypotension were analyzed by 2-sample t test and Wilcoxon rank sum test. Multivariable logistic regression analysis was used to examine the association between clinical variables and elevated chymase levels. RESULTS:Mast cell-specific chymase increased from a median 0.97 pg/mg (interquartile range [IQR], 0.01-1.84 pg/mg) plasma protein at baseline to 5.74 pg/mg (IQR, 2.91-9.48 pg/mg) plasma protein after instituting cardiopulmonary bypass, 6.16 pg/mg (IQR, 3.60-9.41 pg/mg) plasma protein after completing circulatory arrest, and 7.64 pg/mg (IQR, 4.63-12.71 pg/mg) plasma protein after weaning from cardiopulmonary bypass (each P value < .0001 vs baseline). Chymase was the only biomarker associated with hypotension during (P = .0255) and after (P = .0221) cardiopulmonary bypass. Increased temperatures at circulatory arrest and low presurgical hemoglobin levels were independent predictors of increased chymase responses. CONCLUSIONS:Mast cell activation occurs in cardiac surgery requiring cardiopulmonary bypass and hypothermic circulatory arrest and is associated with intraoperative hypotension. 10.1016/j.jtcvs.2016.05.063
    Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest. Rungatscher Alessio,Hallström Seth,Giacomazzi Alice,Linardi Daniele,Milani Elisabetta,Tessari Maddalena,Luciani Giovanni Battista,Scarabelli Tiziano M,Mazzucco Alessandro,Faggian Giuseppe Critical care (London, England) INTRODUCTION:Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS:Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS:The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS:Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA. 10.1186/cc13071
    A study of brain protection during total arch replacement comparing antegrade cerebral perfusion versus hypothermic circulatory arrest, with or without retrograde cerebral perfusion: analysis based on the Japan Adult Cardiovascular Surgery Database. Okita Yutaka,Miyata Hiroaki,Motomura Noboru,Takamoto Shinichi, The Journal of thoracic and cardiovascular surgery OBJECTIVES:Antegrade cerebral perfusion and hypothermic circulatory arrest, with or without retrograde cerebral perfusion, are 2 major types of brain protection that are used during aortic arch surgery. We conducted a comparative study of these methods in patients undergoing total arch replacement to evaluate the clinical outcomes in Japan, based on the Japan Adult Cardiovascular Surgery Database. METHODS:A total of 16,218 patients underwent total arch replacement between 2009 and 2012. Patients with acute aortic dissection or ruptured aneurysm, or who underwent emergency surgery were excluded, leaving 8169 patients for analysis. For the brain protection method, 7038 patients had antegrade cerebral perfusion and 1141 patients had hypothermic circulatory arrest/retrograde cerebral perfusion. A nonmatched comparison was made between the 2 groups, and propensity score analysis was performed among 1141 patients. RESULTS:The matched paired analysis showed that the minimum rectal temperature was lower in the hypothermic circulatory arrest/retrograde cerebral perfusion group (21.2°C ± 3.7°C vs 24.2°C ± 3.2°C) and that the duration of cardiopulmonary bypass and cardiac ischemia was longer in the antegrade cerebral perfusion group. There were no significant differences between the antegrade cerebral perfusion and hypothermic circulatory arrest/retrograde cerebral perfusion groups with regard to 30-day mortality (3.2% vs 4.0%), hospital mortality (6.0% vs 7.1%), incidence of stroke (6.7% vs 8.6%), or transient neurologic disorder (4.1% vs 4.4%). There was no difference in a composite outcome of hospital death, bleeding, prolonged ventilation, need for dialysis, stroke, and infection (antegrade cerebral perfusion 28.4% vs hypothermic circulatory arrest 30.1%). However, hypothermic circulatory arrest/retrograde cerebral perfusion resulted in a significantly higher rate of prolonged stay in the intensive care unit (>8 days: 24.2% vs 15.6%). CONCLUSIONS:Hypothermic circulatory arrest/retrograde cerebral perfusion and antegrade cerebral perfusion provide comparable clinical outcomes with regard to mortality and stroke rates, but hypothermic circulatory arrest/retrograde cerebral perfusion resulted in a higher incidence of prolonged intensive care unit stay. Antegrade cerebral perfusion might be preferred as the brain protection method for complicated aortic arch procedures. 10.1016/j.jtcvs.2014.08.070
    Inhibition of long noncoding RNA growth arrest-specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats. Gao Shilun,Gu Tianxiang,Shi Enyi,Tang Rui,Liu Jinduo,Shi Jiang The Journal of thoracic and cardiovascular surgery OBJECTIVE:We sought to investigate cerebroprotection by targeting long noncoding RNA growth arrest-specific 5 in a rat model of prolonged deep hypothermic circulatory arrest. METHODS:Deep hypothermic circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C in rats. Dual luciferase assay was used to detect the binding relationship between growth arrest-specific 5 and putative target microRNAs. Adeno-associated viral vectors containing growth arrest-specific 5 small interfering RNA or negative control small interfering RNA were administered by intracerebroventricular injection 14 days before deep hypothermic circulatory arrest. Expressions of growth arrest-specific 5, microRNA-23a, phosphate and tension homology, Bcl-2-associated X protein, Bcl-2, phospho-protein kinase B, protein kinase B, and cleaved caspase-3 in the hippocampus were measured by quantitative reverse transcription polymerase chain reaction and Western blot. Spatial learning and memory functions were evaluated by the Morris water maze test. The hippocampus was harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. RESULTS:Luciferase assay showed that growth arrest-specific 5 targeted and inhibited microRNA-23a expression. After deep hypothermic circulatory arrest, hippocampal growth arrest-specific 5 expression was significantly enhanced with a robust decrease of hippocampal microRNA-23a expression. Small interfering RNA growth arrest-specific 5 significantly inhibited growth arrest-specific 5 expression and enhanced microRNA-23a expression in the hippocampus, accompanied with decreases of phosphate and tension homology and Bcl-2-associated X protein expression, and increases of Bcl-2 expression and phospho-protein kinase B/protein kinase B ratio. Growth arrest-specific 5 knockdown inhibited neuronal apoptosis, attenuated histologic damages, and increased the number of surviving neurons in the hippocampus. Spatial learning and memory functions after deep hypothermic circulatory arrest were also markedly improved by growth arrest-specific 5 inhibition. CONCLUSIONS:Inhibition of large noncoding RNA growth arrest-specific 5 can provide a powerful cerebroprotection against deep hypothermic circulatory arrest, which may be mediated through microRNA-23a/phosphate and tension homology pathway. 10.1016/j.jtcvs.2019.01.050
    Cerebral protection during deep hypothermic circulatory arrest: Can a molecular approach via microRNA inhibition improve on a millennia-old strategy? Squiers John J,Arsalan Mani,Lima Brian,DiMaio J Michael The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2015.05.022
    MicroRNA expression in the hippocampal CA1 region under deep hypothermic circulatory arrest. Wang Xiao-Hua,Yao Dong-Xu,Luan Xiu-Shu,Wang Yu,Liu Hai-Xia,Liu Bei,Liu Yang,Zhao Lei,Ji Xun-Ming,Wang Tian-Long Neural regeneration research Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs (miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection (cyclin dependent kinase, CDK16 and SLC1A2), central nervous system development (FOXO3, TYRO3, and SLC1A2), ion transmembrane transporter activity (ATP2B2 and SLC1A2), and interleukin-6 receptor binding (IL6R) - these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017 (approval No. XW-INI-AD2017-0112). 10.4103/1673-5374.253174
    Utility of neuromonitoring in hypothermic circulatory arrest cases for early detection of stroke: Listening through the noise. Ghincea Christian V,Anderson Devon A,Ikeno Yuki,Roda Gavriel F,Eldeiry Mohamed,Bronsert Michael R,Aunkst Kelly,Fullerton David A,Reece T Brett,Aftab Muhammad The Journal of thoracic and cardiovascular surgery OBJECTIVE:Stroke remains a potentially devastating complication of aortic arch intervention. The value of neurophysiologic intraoperative monitoring (NIOM) in the early identification of stroke is unclear. We evaluated the utility of NIOM for early stroke detection in aortic arch surgery. METHODS:Across 8 years at our institution, 365 patients underwent aortic arch surgery with hypothermic circulatory arrest, and 224 cases utilized NIOM. One patient was excluded for intraoperative death. In the remaining cohort, we reviewed the incidence, timing, and location of strokes, and the incidence and nature of NIOM alerts. RESULTS:Hemiarch was performed in 154 patients and total arch replacement in 69 patients. Stroke occurred in 6.3% of all cases (14 out of 223), 15.9% of total arches (11 out of 69), and 2.0% of hemiarches (3 out of 154). There were 33 NIOM alerts (14.8%), and 9 patients had both alerts and stroke. Of these, NIOM deficits plausibly correlated with imaging findings in 7 cases (78%). Of the 5 stroke patients without NIOM alerts, 2 developed neurologic symptoms 3 days or more postoperatively, and infarcts in 3 patients did not result in sensory or motor deficits. Excluding 2 patients with late stroke, the sensitivity of NIOM for stroke detection was 75%, specificity was 88.5%, positive predictive value was 27.3%, and negative predictive value was 97.4%. CONCLUSIONS:Despite a low positive predictive value requiring a high level of discrimination when interpreting abnormal findings, NIOM has high sensitivity and specificity for the early stroke detection. Furthermore, its high negative predictive valve is reassuring for low risk of stroke in the absence of alerts. 10.1016/j.jtcvs.2020.01.090
    Straight deep hypothermic circulatory arrest for cerebral protection during aortic arch surgery: Safe and effective. Ziganshin Bulat A,Rajbanshi Bijoy G,Tranquilli Maryann,Fang Hai,Rizzo John A,Elefteriades John A The Journal of thoracic and cardiovascular surgery OBJECTIVE:To evaluate our extensive clinical experience using deep hypothermic circulatory arrest (DHCA) as a sole method of cerebral protection during aortic arch surgery, with an emphasis on determining the safe duration of DHCA. METHODS:A total of 490 consecutive patients (303 males [61.8%], mean age, 62.7 ± 13.5 years) underwent surgical interventions on the aortic arch with straight DHCA for cerebral protection. Of the procedures, 65 (13.3%) were either urgent or emergency. Aortic aneurysms (n = 417, 85.1%) and dissections (n = 71, 14.5%) were the main indications for surgery. RESULTS:The mean DHCA duration was 29.2 ± 7.9 minutes at a mean bladder temperature of 18.7°C. The overall mortality was 2.4% (12 of 490), and elective mortality was 1.4% (6 of 425). The seizure rate was 1.4% (7 of 490). Six patients (1.2%) developed renal failure that required dialysis. The postoperative stroke rate was 1.6% (8 of 490) and was 1.2% (5 of 425) for the elective cases. The overall stroke rate for patients requiring <50 minutes of DHCA was 1.3% (6 of 478), significantly different from the 16.7% (2 of 12) stroke rate for patients requiring >50 minutes of DHCA (P = .014). Multivariate analysis revealed a DHCA time >50 minutes (odds ratio, 5.11 ± 4.01, P = .038) and aortic dissection (odds ratio, 3.59 ± 1.72, P = .008) to be strong predictors of composite adverse outcomes. CONCLUSIONS:Straight DHCA is a safe and effective technique of cerebral protection for the absolute majority of interventions involving the aortic arch. At experienced centers, up to 50 minutes of DHCA can be considered safe, without significant postoperative mortality or neurologic sequelae. 10.1016/j.jtcvs.2014.05.027
    Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest. Wang Yongchao,Gu Tianxiang,Shi Enyi,Yu Lei,Wang Chun,Zhang Yuhai,Fang Qin The Journal of thoracic and cardiovascular surgery OBJECTIVE:We sought to investigate the cerebroprotection of a novel microRNA mechanism by targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha in a rat model of prolonged deep hypothermia circulatory arrest. METHODS:The right carotid artery and jugular vein of male Sprague-Dawley rats were cannulated for cardiopulmonary bypass. Circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. The sham group received the surgical procedure without cardiopulmonary bypass and deep hypothermia circulatory arrest; the deep hypothermia circulatory arrest group received cardiopulmonary bypass and deep hypothermia circulatory arrest; lentivirus control vector or lentiviral vector containing antagomiR-29c was given to the deep hypothermia circulatory arrest + vector group or the deep hypothermia circulatory arrest + antagomiR-29c group by intracerebroventricular administration 5 days before cardiopulmonary bypass (n = 8, for each of the 4 groups). Neurologic function was evaluated by the modified hole board test and beam balance task during 14 postoperative days. Expressions of caspase-3, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and miR-29c in the hippocampus were measured by Western blot and quantitative reverse transcription polymerase chain reaction. Malondialdehyde was measured using the Malondialdehyde Assay Kit (Beyotime, Jiangsu, China). RESULTS:Pretreatment with antagomiR-29c significantly decreased the expression of microRNA-29c and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha in the hippocampus (P < .05 vs deep hypothermia circulatory arrest group). The level of malondialdehyde in the hippocampus was lower in the deep hypothermia circulatory arrest + antagomiR-29c group (P < .05 vs deep hypothermia circulatory arrest group). The neurologic functions were markedly protected in rats pretreated with antagomiR-29c as evidenced by improvement of vestibulomotor and cognitive performance during the early postoperative period. In the deep hypothermia circulatory arrest + antagomiR-29c group, histologic scores of the hippocampus were improved and the level of caspase-3 in the hippocampus was lower (P < .05 vs deep hypothermia circulatory arrest group). CONCLUSIONS:Inhibition of miR-29c attenuates neurologic injuries induced by prolonged deep hypothermia circulatory arrest through a peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway. 10.1016/j.jtcvs.2015.04.062
    Straight deep hypothermic circulatory arrest for aortic arch surgery: Going the way of the dinosaurs? Kouchoukos Nicholas T The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2017.08.044
    Straight deep hypothermic circulatory arrest: Should we definitively give up or should we keep on? Formica Francesco,D'Alessandro Stefano,Messina Luigi Amerigo The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2017.12.047
    Aortic arch surgery with hypothermic circulatory arrest and unilateral antegrade cerebral perfusion: Perioperative outcomes. Wang Xiaomeng,Yang Feng,Zhu Junming,Liu Yongmin,Sun Lizhong,Hou Xiaotong The Journal of thoracic and cardiovascular surgery OBJECTIVE:The study objective was to determine the effects of surgical procedures, circulatory management strategies, and cerebral protection strategies on the short-term outcomes of aortic arch surgery based on the 7-year clinical experience of a single center. METHODS:We analyzed the data of 1708 patients who underwent aortic arch surgery with definite hypothermic circulatory arrest and unilateral antegrade cerebral perfusion at Beijing Anzhen Hospital between 2009 and 2015. Logistic regression and random Forest regression analyses were used to determine predictors and their effects on outcomes. RESULTS:Thirty-day mortality was 6.1%. Permanent neurologic dysfunction incidence was 4.8%. The proportion of patients requiring continuous renal replacement therapy was 7.9%. In multivariable analyses, age, DeBakey type I dissection, New York Heart Association score, coma, coronary artery bypass grafting, extra-anatomic bypass, and cardiopulmonary bypass time were independent risk factors for mortality. Age, DeBakey type I dissection, and cardiopulmonary bypass time were independent risk factors for permanent neurologic dysfunction. In the random Forest regression, the risk for permanent neurologic dysfunction and mortality increased when unilateral antegrade cerebral perfusion time was more than 38 minutes and decreased with an increase in nasopharyngeal temperature when temperature was lower than approximately 24°C. The risk for permanent neurologic dysfunction, continuous renal replacement therapy, and paraplegia increased when temperature was greater than approximately 24°C. CONCLUSIONS:The study showed that the largest reported cohort of patients undergoing aortic arch surgery with hypothermic circulatory arrest and unilateral antegrade cerebral perfusion had reasonable morbidity and mortality rates. As a cerebral protection strategy, unilateral antegrade cerebral perfusion may have a 38-minute safety threshold. Moderate hypothermia should be maintained below 24°C to reduce the risk for permanent neurologic dysfunction, paraplegia, and acute renal dysfunction requiring continuous renal replacement therapy. 10.1016/j.jtcvs.2019.01.127
    Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion combined with deep hypothermia circulatory arrest in aortic arch surgery: a meta-analysis and systematic review of 5060 patients. Hu Zhipeng,Wang Zhiwei,Ren Zongli,Wu Hongbing,Zhang Min,Zhang Hao,Hu Xiaoping The Journal of thoracic and cardiovascular surgery OBJECTIVE:Our objective was to determine if antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP) combined with deep hypothermia circulatory arrest in aortic arch surgery results in different mortality and neurologic outcomes. METHODS:The Cochrane Library, Medline, EMBASE, CINAHL, Web of Science, and the Chinese Biomedical Database were searched for studies reporting on postoperative strokes, permanent neurologic dysfunction, temporary neurologic dysfunction, and all causes mortality within 30 days postoperation in aortic arch surgery. Meta-analysis for effect size, t test, and I(2) for detecting heterogeneity and sensitivity analysis for assessing the relative influence of each study was performed. RESULTS:Fifteen included studies encompassed a total of 5060 patients of whom 2855 were treated with deep hypothermic circulatory arrest plus ACP and 1897 were treated with deep hypothermic circulatory arrest plus RCP. Pooled analysis showed no significant statistical difference (P > .01) of 30-day mortality, permanent neurologic dysfunction, and transient neurologic dysfunction in the 2 groups. Before sensitivity analysis, postoperative stroke incidence in the ACP group was higher than in the RCP group (7.2% vs 4.7%; P < .01). After a study that included a different percentage of patients with a history of central neurologic events in the 2 groups was ruled out, postoperative stroke incidence in the 2 groups also showed no significant statistical difference (P > .01). CONCLUSIONS:ACP and RCP provide similar cerebral protective effectiveness combined with deep hypothermia circulatory arrest and could be selected according to the actual condition in aortic arch surgery. A high-quality randomized controlled trial is urgently needed to confirm this conclusion, especially for stroke morbidity following ACP or RCP. 10.1016/j.jtcvs.2013.10.036
    Antegrade versus retrograde cerebral perfusion for hemiarch replacement with deep hypothermic circulatory arrest: does it matter? A propensity-matched analysis. Ganapathi Asvin M,Hanna Jennifer M,Schechter Matthew A,Englum Brian R,Castleberry Anthony W,Gaca Jeffrey G,Hughes G Chad The Journal of thoracic and cardiovascular surgery OBJECTIVE:The choice of cerebral perfusion strategy for aortic arch surgery has been debated, and the superiority of antegrade (ACP) or retrograde (RCP) cerebral perfusion has not been shown. We examined the early and late outcomes for ACP versus RCP in proximal (hemi-) arch replacement using deep hypothermic circulatory arrest (DHCA). METHODS:A retrospective analysis of a prospectively maintained database was performed for all patients undergoing elective and nonelective hemiarch replacement at a single referral institution from June 2005 to February 2013. Total arch cases were excluded to limit the analysis to shorter DHCA times and a more uniform patient population for whom clinical equipoise regarding ACP versus RCP exists. A total of 440 procedures were identified, with 360 (82%) using ACP and 80 (18%) using RCP. The endpoints included 30-day/in-hospital and late outcomes. A propensity score with 1:1 matching of 40 pre- and intraoperative variables was used to adjust for differences between the 2 groups. RESULTS:All 80 RCP patients were propensity matched to a cohort of 80 similar ACP patients. The pre- and intraoperative characteristics were not significantly different between the 2 groups after matching. No differences were found in 30-day/in-hospital mortality or morbidity outcomes. The only significant difference between the 2 groups was a shorter mean operative time in the RCP cohort (P = .01). No significant differences were noted in late survival (P = .90). CONCLUSIONS:In proximal arch operations using DHCA, equivalent early and late outcomes can be achieved with RCP and ACP, although the mean operative time is significantly less with RCP, likely owing to avoidance of axillary cannulation. Questions remain regarding comparative outcomes with straight DHCA and lesser degrees of hypothermia. 10.1016/j.jtcvs.2014.04.014
    Is there a need for adjunct cerebral protection in conjunction with deep hypothermic circulatory arrest during noncomplex hemiarch surgery? Kaneko Tsuyoshi,Aranki Sary F,Neely Robert C,Yazdchi Farhang,McGurk Siobhan,Leacche Marzia,Shekar Prem S The Journal of thoracic and cardiovascular surgery OBJECTIVE:Different cerebral protection strategies are currently being practiced during noncomplex hemiarch surgery without randomized control studies to show their relative efficacy. We hypothesized that deep hypothermic circulatory arrest (DHCA) alone was adequate for cerebral protection in noncomplex hemiarch surgery. METHODS:Four hundred sixty-seven patients underwent noncomplex hemiarch surgery between January 2002 and December 2012. Calcified aortas and total arch surgeries were excluded. DHCA alone was used for 276 patients, DHCA with antegrade cerebral perfusion (ACP) was used for 114 patients, and DHCA with retrograde cerebral perfusion (RCP) was used for 77 patients. RESULTS:Preoperative characteristics were similar between groups (12.3% in the DHCA group, 12.3% in the ACP group, and 10.3% in RCP group were reoperations). Patients in the DHCA group had shorter cardiopulmonary bypass times (193 minutes vs 217 minutes; P ≤ .005) and total lower body ischemic times (21 minutes vs 30 minutes; P ≤ .001) than ACP, but not RCP. Rates of reoperations for bleeding, postoperative stroke, and new renal failure did not differ between groups. New onset of cerebrovascular events were seen in 5.4% of patients in the DHCA group versus 6.2% of patients in the ACP group and 6.4% of patients in the RCP group (all P values > .7). Operative mortality in the DHCA group was 4.7% versus 2.6% in the ACP group and 2.6% in the RCP group (all P values > .4). Cox proportional hazard modeling showed no survival differences between groups. CONCLUSIONS:Outcomes and survival using DHCA alone were comparable to adjunct cerebral protection methods in patients undergoing noncomplex hemiarch surgery. DHCA alone is as safe as other adjunct complex cerebral protection techniques and simplifies operation without additional risk. 10.1016/j.jtcvs.2014.08.010
    Data support continued role for straight deep hypothermic circulatory arrest. Damberg Anneke,Ziganshin Bulat A,Elefteriades John A The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2017.12.123
    Does the brain need an enema during deep hypothermic circulatory arrest? Elefteriades John A,Ziganshin Bulat A The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2018.05.091
    Straight deep hypothermic circulatory arrest: Cling to old fashion or not? Yan Shujie,Ji Bingyang,Lou Song The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2018.01.001
    Deep hypothermic circulatory arrest is not a risk factor for acute kidney injury in thoracic aortic surgery. Englberger Lars,Suri Rakesh M,Greason Kevin L,Burkhart Harold M,Sundt Thoralf M,Daly Richard C,Schaff Hartzell V The Journal of thoracic and cardiovascular surgery OBJECTIVE:Previous studies describe a high incidence of acute kidney injury after open thoracic aortic surgery. Findings may be confounded by patient selection, including surgery with deep hypothermic circulatory arrest only or emergency procedures. We studied incidence and risk factors of acute kidney injury in patients undergoing thoracic aortic surgery. METHODS:We reviewed 851 patients undergoing elective thoracic aortic surgery with and without deep hypothermic circulatory arrest between 2000 and 2007, focusing on clinical outcome and acute kidney injury defined by consensus RIFLE (Risk, Injury, Failure, Loss of function, End-stage renal disease) criteria. RESULTS:Mean age was 59±16 years; 29% were women. Surgical procedures included aortic root or ascending aorta in 817 patients (96%), aortic arch in 172 (20%), and descending thoracic aorta in 54 (6%), with 20% reoperative procedures. Deep hypothermic circulatory arrest was used in 238 (28%). Incidence of postoperative acute kidney injury (all RIFLE classes) was 17.7%; 2.1% required renal replacement therapy. Mortality increased with RIFLE class severity of acute kidney injury (P<.001). Independent risk factors for acute kidney injury were increased age, elevated body mass index, hypertension, impaired left ventricular ejection fraction, preoperative anemia, and cardiopulmonary bypass duration. Deep hypothermic circulatory arrest, aprotinin use, and preoperative creatinine level were not independently associated with acute kidney injury. CONCLUSIONS:Thoracic aortic surgery can be performed with low rates of acute kidney injury, comparable to other cardiac surgical procedures. Deep hypothermic circulatory arrest and preoperative serum creatinine are not independent risk factors. RIFLE criteria allow comparison with previous studies and correlate well with patient outcome. Risk estimates for acute kidney injury require multivariable prediction. 10.1016/j.jtcvs.2010.02.045
    Direct innominate artery cannulation for selective antegrade cerebral perfusion during deep hypothermic circulatory arrest in aortic surgery. Garg Vinay,Tsirigotis Dimitrios N,Dickson Jeff,Dalamagas Constantine,Latter David A,Verma Subodh,Peterson Mark D The Journal of thoracic and cardiovascular surgery OBJECTIVE:To demonstrate a novel, reproducible, and effective method of direct innominate artery cannulation using a 14 F pediatric venous cannula to establish antegrade cerebral protection (ACP) in patients undergoing aortic surgery that requires an open distal anastomosis or hemiarch replacement. METHODS:We reviewed prospectively gathered data on all patients who had undergone replacement of the ascending aorta or hemiarch with an open distal anastomosis using deep hypothermic circulatory arrest and direct innominate artery cannulation with a 14 F pediatric venous cannula at our institution. After central cannulation and cooling to 25 °C to 28 °C, all patients had ACP initiated by way of a direct innominate cannula placed over a guidewire. RESULTS:Fifty patients underwent direct innominate artery cannulation with our technique from 2010 to 2012. The operative mortality was 2% (n = 1), and the rates of neurologic morbidity were acceptable and similar to those with other methods of ACP delivery: stroke (2%, n = 1), seizure (0%, n = 0), and delirium (18%, n = 9). The mean operative time was 31 ± 9, 19 ± 5, 100 ± 39, 141 ± 39, and 259 ± 63 minutes for cooling, circulatory arrest, crossclamp, cardiopulmonary bypass, and total operative time, respectively. No local or arterial complications were observed. CONCLUSIONS:Direct cannulation of the innominate artery using a 14 F pediatric venous cannula is a simple, reproducible, safe, and effective technique for establishing ACP in patients undergoing aortic surgery that requires an open distal anastomosis or hemiarch replacement. This technique avoids the additional time and potential local complications associated with other established methods for delivering ACP, such as axillary cannulation. 10.1016/j.jtcvs.2014.07.021
    Use of human fibrinogen concentrate during proximal aortic reconstruction with deep hypothermic circulatory arrest. Hanna Jennifer M,Keenan Jeffrey E,Wang Hanghang,Andersen Nicholas D,Gaca Jeffrey G,Lombard Frederick W,Welsby Ian J,Hughes G Chad The Journal of thoracic and cardiovascular surgery OBJECTIVE:Human fibrinogen concentrate (HFC) is approved by the Food and Drug Administration for use at 70 mg/kg to treat congenital afibrinogenemia. We sought to determine whether this dose of HFC increases fibrinogen levels in the setting of high-risk bleeding associated with aortic reconstruction and deep hypothermic circulatory arrest (DHCA). METHODS:This was a prospective, pilot, off-label study in which 22 patients undergoing elective proximal aortic reconstruction with DHCA were administered 70 mg/kg HFC upon separation from cardiopulmonary bypass (CPB). Fibrinogen levels were measured at baseline, just before, and 10 minutes after HFC administration, on skin closure, and the day after surgery. The primary study outcome was the difference in fibrinogen level immediately after separation from CPB, when HFC was administered, and the fibrinogen level 10 minutes following HFC administration. Additionally, postoperative thromboembolic events were assessed as a safety analysis. RESULTS:The mean baseline fibrinogen level was 317 ± 49 mg/dL and fell to 235 ± 39 mg/dL just before separation from CPB. After HFC administration, the fibrinogen level rose to 331 ± 41 mg/dL (P < .001) and averaged 372 ± 45 mg/dL the next day. No postoperative thromboembolic complications occurred. CONCLUSIONS:Administration of 70 mg/kg HFC upon separation from CPB raises fibrinogen levels by approximately 100 mg/dL without an apparent increase in thrombotic complications during proximal aortic reconstruction with DHCA. Further prospective study in a larger cohort of patients will be needed to definitively determine the safety and evaluate the efficacy of HFC as a hemostatic adjunct during these procedures. 10.1016/j.jtcvs.2015.08.079
    Adjunct retrograde cerebral perfusion provides superior outcomes compared with hypothermic circulatory arrest alone: A meta-analysis. Tian David H,Weller Justin,Hasmat Shaheen,Oo Aung,Forrest Paul,Kiat Hosen,Yan Tristan D The Journal of thoracic and cardiovascular surgery OBJECTIVE:Retrograde cerebral perfusion is becoming less frequently used as a method of neuroprotection during aortic surgery. The present meta-analysis aims to compare outcomes after arch surgery with hypothermic circulatory arrest versus hypothermic circulatory arrest + retrograde cerebral perfusion. METHODS:Electronic searches were performed using 7 databases from their inception to September 2016. Relevant comparative studies that included patient groups who underwent aortic arch surgery using hypothermic circulatory arrest with continuous retrograde cerebral perfusion or hypothermic circulatory arrest alone were identified, and data were extracted by 2 independent researchers. Data were aggregated using a random-effects model per predefined clinical end points. RESULTS:Twenty-eight comparative studies were identified, with 2705 hypothermic circulatory arrest cases and 2817 hypothermic circulatory arrest + retrograde cerebral perfusion cases. No significant differences were seen between both groups in terms of age, gender, proportion of dissections and aneurysms, and hemiarch/total arch repair. The hypothermic circulatory arrest + retrograde cerebral perfusion group had slightly longer cardiopulmonary bypass time and lower body arrest time. Mortality was significantly increased for the hypothermic circulatory arrest cohort compared with the hypothermic circulatory arrest + retrograde cerebral perfusion cohort (odds ratio, 1.75; 95% confidence interval, 1.16-2.63; P = .007; I = 54%), but not on pooling of adjusted estimates. Stroke was also increased for the hypothermic circulatory arrest cohort (odds ratio, 1.50; 95% confidence interval, 1.07-2.10; P = .02; I = 29%). No difference in temporary neurologic deficit was identified (P = .66). Meta-regression found the treatment effect for mortality and stroke to be less pronounced in more contemporary series. CONCLUSIONS:These results suggest that the addition of retrograde cerebral perfusion during aortic arch surgery may provide better outcomes than using hypothermic circulatory arrest alone, although significant confounders exist. Further robust studies are required to confirm the utility of retrograde cerebral perfusion in arch surgery. 10.1016/j.jtcvs.2018.04.063
    Commentary: U-CIRP-ing the neurological effects of deep hypothermic circulatory arrest. Sorabella Robert,Si Ming-Sing The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2019.08.076
    The neurologic protection of unilateral versus bilateral antegrade cerebral perfusion in aortic arch surgery with deep hypothermic circulatory arrest: A study of 77 cases. Li Bowen,Hu Xiaoping,Wang Zhiwei International journal of surgery (London, England) BACKGROUD:Unilateral and bilateral antegrade cerebral perfusions (ACP) are recognized methods of cerebral protection in aortic arch surgery. However, the adequacy of cerebral protection in aortic arch surgery with deep hypothermic circulatory arrest is controversial. In this study, we compared unilateral and bilateral ACP of cerebral protection in aortic arch surgery by assessing the patient's intraoperative and postoperative brain function. METHODS:A total of 77 patients undergoing aortic arch surgery were included in this study. Unilateral ACP was performed using a cannula in the innominate artery (n = 40), whereas bilateral ACP was conducted using an additional cannula in the left carotid artery (n = 37). Levels of S-100β and neuron specific enolase (NSE) were assayed at the beginning of cardiopulmonary bypass (T1), the beginning of circulatory arrest (T2), and post ACP at T = 25 min (T3), the end of ACP (T4), the end of cardiopulmonary bypass (T5), and at T = 1 h (T6), T = 6 h (T7), and T = 24 h (T8). Transcranial Doppler ultrasonography was used both preoperatively and intraoperatively to detect the blood flow of bilateral middle cerebral artery (MCA), and neurologic deficit incidence and mortality rates were obtained. RESULTS:At time points T1, T2, and T3, plasma levels of S-100β and NSE were not statistically different between groups. However, S-100β and NSE levels for each time point ranging from T = T4 to T = T8 did show statistically significant differences between groups. Patients who with one side of the middle cerebral artery stenosis, used bilateral antegrade cerebral perfusions method, intraoperative Transcranial Doppler ultrasonography examination showed narrow side blood flow weaker than the normal side during the deep hypothermic circulatory arrest (DHCA), however no significant differences could be observed between the two sides (P > 0.05). The incidence of neurological dysfunction was higher in the unilateral ACP group compared to the bilateral ACP group (25% vs. 8.11%, respectively, P = 0.028). Moreover, no marked differences were observed in mortality (2.5% vs. 5.41%, respectively, P = 1.000). CONCLUSIONS:When the duration of DHCA was 25 min or less, no significant differences were observed between unilateral and bilateral ACP. However, when DHCA exceeded 25 min, bilateral ACP was more effective compared to unilateral ACP. Due to the high variations in circle of Willis as well as increased safety, simplicity, and efficiency, the bilateral ACP approach is preferred over the unilateral technique. 10.1016/j.ijsu.2017.02.023
    Favorable late survival after aortic surgery under straight deep hypothermic circulatory arrest. Damberg Anneke,Carino Davide,Charilaou Paris,Peterss Sven,Tranquilli Maryann,Ziganshin Bulat A,Rizzo John A,Elefteriades John A The Journal of thoracic and cardiovascular surgery BACKGROUND:Surgical and cerebral protection strategies in aortic arch surgery remain under debate. Perioperative results using deep hypothermic circulatory arrest (DHCA) have been associated with favorable short-term mortality and stroke rates. The present study focuses on late survival in patients undergoing aortic surgery using DHCA. METHODS:A total of 613 patients (mean age, 63.7 years) underwent aortic surgery between January 2003 and December 2015 using DHCA, with 77.3% undergoing hemiarch replacement and 20.4% undergoing arch replacement, with a mean DHCA duration of 29.7 ± 8.5 minutes (range, 10-62 minutes). We examined follow-up extending up to a mean of 3.8 ± 3.4 years (range, 0-14.1 years). RESULTS:Operative mortality was 2.9%, and the stroke rate was 2%. Survival was 92.2% at 1 year and 81.5% at 5 years, significantly lower than the values in an age- and sex-matched reference population. In elective, nondissection first-time surgeries (n = 424), survival was similar to that of the reference group. Acute type A aortic dissection (hazard ratio [HR], 4.84; P = .000), redo (HR, 4.12; P = .000), and descending aortic pathology (HR, 5.54: P = .000) were independently associated with reduced 1-year survival. Beyond 1 year, age (HR, 1.07; P = .000), major complications (HR, 3.11; P = .000), and atrial fibrillation (HR, 2.47; P = .006) were independently associated with poor survival. DHCA time was not significantly associated with survival in multivariable analysis. CONCLUSIONS:Aortic surgery with DHCA can be performed with favorable late survival, with the duration of DHCA period having only a limited impact. However, these results cannot be generalized for very long durations of DHCA (>50 minutes), when perfusion methods may be preferable. In elective, nondissection first-time surgeries, a late survival comparable to that in a reference population can be achieved. Early survival is adversely affected by aortic dissection, redo status, and disease extent. 10.1016/j.jtcvs.2017.08.015
    Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy. Hanley Frank L,Ito Hiroki,Gu Meng,Hurd Ralph,Riemer R Kirk,Spielman Daniel The Journal of thoracic and cardiovascular surgery 10.1016/j.jtcvs.2019.10.103
    Effect of granulocyte-colony stimulating factor on expression of selected proteins involved in regulation of apoptosis in the brain of newborn piglets after cardiopulmonary bypass and deep hypothermic circulatory arrest. Pastuszko Peter,Schears Gregory J,Pirzadeh Afsaneh,Kubin Joanna,Greeley William J,Wilson David F,Pastuszko Anna The Journal of thoracic and cardiovascular surgery OBJECTIVE:The study objective was to investigate the effect of granulocyte-colony stimulating factor on the expression of proteins that regulate apoptosis in newborn piglet brain after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS:The newborn piglets were assigned to 3 groups: (1) deep hypothermic circulatory arrest (30 minutes of deep hypothermic circulatory arrest, 1 hour of low-flow cardiopulmonary bypass); (2) deep hypothermic circulatory arrest with prior injection of granulocyte-colony stimulating factor (17 μg/kg 2 hours before cardiopulmonary bypass); and (3) sham-operated. After 2 hours of post-bypass recovery, the frontal cortex, striatum, and hippocampus were dissected. The expression of proteins was measured by gel electrophoresis or protein arrays. Data are presented in arbitrary units. Statistical analysis was performed using 1-way analysis of variance. RESULTS:In the frontal cortex, only Fas ligand expression was significantly lower in the granulocyte-colony stimulating factor group when compared with the deep hypothermic circulatory arrest group. In the hippocampus, granulocyte-colony stimulating factor increased Bcl-2 (54.3 ± 6.4 vs 32.3 ± 2.2, P = .001) and serine/threonine-specific protein kinase (141.4 ± 19 vs 95.9 ± 21.1, P = .047) when compared with deep hypothermic circulatory arrest group. Caspase-3, Bax, Fas, Fas ligand, death receptor 6, and Janus protein tyrosine kinase 2 levels were unchanged. The Bcl-2/Bax ratio was 0.33 for deep hypothermic circulatory arrest group and 0.93 for the granulocyte-colony stimulating factor group (P = .02). In the striatum, when compared with the deep hypothermic circulatory arrest group, the granulocyte-colony stimulating factor group had higher levels of Bcl-2 (50.3 ± 7.4 vs 31.8 ± 3.8, P = .01), serine/threonine-specific protein kinase (132.7 ± 12.3 vs 14 ± 1.34, P = 2.3 × 10(6)), and Janus protein tyrosine kinase 2 (126 ± 17.4 vs 77.9 ± 13.6, P = .011), and lower levels of caspase-3 (12.8 ± 5.0 vs 32.2 ± 11.5, P = .033), Fas (390 ± 31 vs 581 ± 74, P = .038), Fas ligand (20.5 ± 11.5 vs 57.8 ± 15.6, P = .04), and death receptor 6 (57.4 ± 4.4 vs 108.8 ± 13.4, P = .007). The Bcl-2/Bax ratio was 0.25 for deep hypothermic circulatory arrest and 0.44 for the granulocyte-colony stimulating factor groups (P = .046). CONCLUSIONS:In the piglet model of hypoxic brain injury, granulocyte-colony stimulating factor decreases proapoptotic signaling, particularly in the striatum. 10.1016/j.jtcvs.2012.01.018
    Deep hypothermic circulatory arrest: real-life suspended animation. Chau Katherine H,Ziganshin Bulat A,Elefteriades John A Progress in cardiovascular diseases Deep hypothermic circulatory arrest (DHCA) is a cerebral protection technique that was developed in the 1950s and popularized in the 1970s. It has become one of the three most common cerebral protection techniques currently used in aortic arch surgeries, with the other two being antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). At our institution, DHCA has been the cerebral protection technique of choice for over a quarter century. Our clinical experience with DHCA has been very positive, and our clinical studies have shown DHCA to have outcomes equal to (and sometimes better than) those of ACP and RCP, and DHCA to be very effective at preserving neurocognitive function. Other institutions, however, prefer ACP or RCP to DHCA. Each technique has its own set of pros and cons, and the question regarding which technique is the superior method for cerebral protection is hotly debated. 10.1016/j.pcad.2013.05.009
    Protection of the rat brain from hypothermic circulatory arrest injury by a chipmunk protein. Jiang Xuan,Gu Tianxiang,Liu Yu,Wang Chun,Shi Enyi,Zhang Guangwei,Xiu Zongyi The Journal of thoracic and cardiovascular surgery OBJECTIVES:The study objectives were to test the hypothesis that special protein exists in hibernating chipmunk albumin and whether this protein has a neuroprotective effect in Sprague-Dawley rats during deep hypothermia circulatory arrest. METHODS:Forty chipmunks were allocated into a hibernation group and an active group (20 chipmunks in each group). Special protein was detected and isolated from hibernating chipmunk albumin. Forty Sprague-Dawley rats were randomly divided into a sham group, deep hypothermia circulatory arrest group, special protein group, and naloxone group (10 rats in each group). Special protein that was detected and collected from hibernating chipmunks were injected in rats in the special protein group for 3 consecutive days before operation, and naloxone was given at the same time in the naloxone group. Rats were subjected to cardiopulmonary bypass and 60-minute deep hypothermia circulatory arrest. Tumor necrosis factor-α and interleukin-6 levels were detected. Animals received neurologic testing. Relative protein expression, malondialdehyde, and superoxide dismutase of hippocampus were detected. The brain was fixed for histopathologic assessment. RESULTS:The rats that received special protein displayed ischemic tolerance after deep hypothermia circulatory arrest. The neuroprotective effect could be reversed by naloxone. The inflammation response was attenuated in the special protein group (P < .008, compared with the deep hypothermia circulatory arrest and naloxone groups). The mature brain-derived neurotrophic factor and SIRT1 levels were higher in the special protein group (P < .01, compared with the deep hypothermia circulatory arrest and naloxone groups). Histopathologic assessment showed that the injury in the special protein group was attenuated (pathological score, P < .05; surviving hippocampal CA1 neurons, P < .01; TUNEL-positive neurons, P < .01; compared with deep hypothermia circulatory arrest and naloxone groups). Intravenous injection of special protein significantly improved neurologic recovery. CONCLUSIONS:We found that a specific protein existed in hibernating chipmunk albumin and could play an important neuroprotective role in rats. 10.1016/j.jtcvs.2018.02.048
    Deep hypothermic circulatory arrest during the arterial switch operation is associated with reduction in cerebral oxygen extraction but no increase in white matter injury. Drury Paul P,Gunn Alistair J,Bennet Laura,Ganeshalingham Anusha,Finucane Kirsten,Buckley David,Beca John The Journal of thoracic and cardiovascular surgery OBJECTIVE:Deep hypothermic circulatory arrest may be associated with increased neural injury. We investigated whether short periods of deep hypothermic circulatory arrest are associated with altered neurophysiologic recovery or greater risk of injury. METHODS:Eighteen term infants with transposition of the great arteries undergoing the arterial switch operation were enrolled. Deep hypothermic circulatory arrest was used in 11, and bypass alone in 7. Near-infrared spectroscopy and amplitude-integrated electroencephalography were recorded with standard monitoring during and from 4 to 16 h after surgery. Fractional tissue oxygen extraction was determined from arterial oxygen saturation and venous weighted intracerebral oxygenation. Magnetic resonance imaging was performed before and 5 to 7 days after surgery. RESULTS:There were no significant differences between patients requiring deep hypothermic circulatory arrest (median, 5 min; range, 3-6 min) or cardiopulmonary bypass only at the beginning of surgery. At the end of surgery, amplitude-integrated electroencephalography minimum amplitude was significantly lower in the deep hypothermic circulatory arrest group (P < .05), and fractional tissue oxygen extraction tended to be lower (P = .068). After surgery, deep hypothermic circulatory arrest was associated with significantly higher tissue oxygenation index, lower fractional tissue oxygen extraction, and lower core temperature (P < .05). Magnetic resonance imaging-defined white matter injuries before and after surgery were similar between groups. CONCLUSIONS:In this prospective, observational study, brief deep hypothermic circulatory arrest during arterial switch was associated with reduced cerebral oxygen uptake during recovery, with transient electroencephalographic suppression but no increase in risk of white matter injury. 10.1016/j.jtcvs.2013.02.011
    Is selective antegrade cerebral perfusion superior to retrograde cerebral perfusion for brain protection during deep hypothermic circulatory arrest? Metabolic evidence from microdialysis. Liang Meng-Ya,Tang Zhi-Xian,Chen Guang-Xian,Rong Jian,Yao Jian-Ping,Chen Zhen,Wu Zhong-Kai Critical care medicine OBJECTIVES:This study aimed to investigate whether selective antegrade cerebral perfusion or retrograde cerebral perfusion is a better technique for brain protection in deep hypothermic circulatory arrest by obtaining metabolic evidence from microdialysis. DESIGN:Randomized, animal study. SETTING:Assisted circulation laboratory. SUBJECTS:Eighteen piglets of either sex (9.8 ± 3.1 kg). INTERVENTIONS:Animals were randomly assigned to 40 minutes of circulatory arrest at 18°C without cerebral perfusion (deep hypothermic circulatory arrest group, n = 6) or with selective antegrade cerebral perfusion (selective antegrade cerebral perfusion group, n = 6) or retrograde cerebral perfusion (retrograde cerebral perfusion group, n = 6). Reperfusion was continued for 3 hours. MEASUREMENTS AND MAIN RESULTS:Microdialysis (glucose, lactate, pyruvate, and glycerol) variables in the cortex dialysate were measured every 30 minutes. Intracerebral pressure and serum S-100 levels were also monitored. After 3 hours of reperfusion, cortical tissue was harvested for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. After 40 minutes of circulatory arrest, the deep hypothermic circulatory arrest group presented marked elevations of intracerebral pressure, and serum S-100 levels were higher in the deep hypothermic circulatory arrest group than in the other two groups (p < 0.001, respectively). The selective antegrade cerebral perfusion group exhibited higher glucose, lower lactate, and lower glycerol levels and a lower lactate-to-pyruvate ratio in comparison to the deep hypothermic circulatory arrest group (p < 0.05, respectively); the retrograde cerebral perfusion group had lower lactate and glycerol levels and a lower lactate-to-pyruvate ratio (p < 0.05, respectively) but similar glucose levels compared to deep hypothermic circulatory arrest alone. Furthermore, selective antegrade cerebral perfusion provided better preservation of energy and cell integrity than retrograde cerebral perfusion with higher glucose and lower glycerol levels (p < 0.05, respectively). After 3 hours of reperfusion, fewer apoptotic neurons were found in selective antegrade cerebral perfusion animals than in the other two groups (p < 0.05, respectively). CONCLUSIONS:Both selective antegrade cerebral perfusion and retrograde cerebral perfusion were superior to deep hypothermic circulatory arrest alone during circulatory arrest. Retrograde cerebral perfusion was a moderate technique that had similar advantages with regard to less cerebral edema, better clearance of metabolic waste, and lower levels of biomarkers of injury than selective antegrade cerebral perfusion, but its capacity for energy preservation, maintenance of cellular integrity, and protection against apoptosis was lower than that of selective antegrade cerebral perfusion. 10.1097/CCM.0000000000000220
    Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion. Kajimoto Masaki,Ledee Dolena R,Olson Aaron K,Isern Nancy G,Robillard-Frayne Isabelle,Des Rosiers Christine,Portman Michael A Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. 10.1177/0271678X16666846
    Triptolide improves neurobehavioral functions, inflammation, and oxidative stress in rats under deep hypothermic circulatory arrest. Chen Qiang,Lei Yu-Qing,Liu Jian-Feng,Wang Zeng-Chun,Cao Hua Aging This study investigated the neuroprotective effects of triptolide (TPL) in a rat model of cardiopulmonary bypass with deep hypothermia circulatory arrest (DHCA). Rats were randomly divided into six groups: control, sham, DHCA, and DHCA + TPL (100, 200, 300 μg/kg). Neurobehavioral functions were measured using the elevated plus-maze, Y-maze, and Morris water maze tests. Levels of inflammatory cytokines, oxidative stress indices, and brain neurotrophins were measured by ELISA. Microglial activation and cell death was measured by immunofluorescence staining and TUNEL assay, respectively. Finally, activation of the Nrf2 pathway and NF-κB were detected by western blot. The elevated plus-maze, Y-maze, and Morris water maze tests all showed that TPL mitigated anxiety-like behavior, working memory, spatial learning, and memory in DHCA rats. TPL inhibited inflammatory responses and oxidative stress, as well as increased brain neurotrophin levels in DHCA rats. Moreover, TPL attenuated microglia activation and cell death in DHCA rats. Finally, TPL activated the Nrf2 pathway and inhibited NF-κB activity in DHCA rats. These results demonstrated that TPL improved neurobehavioral functions, neuroinflammation, and oxidative stress in DHCA rats, which may be associated with the Nrf2 and NF-κB pathways. 10.18632/aging.202460
    Transcriptome profiling reveals activation of inflammation and apoptosis in the neonatal striatum after deep hypothermic circulatory arrest. Tu Lan N,Timms Andrew E,Kibiryeva Nataliya,Bittel Douglas,Pastuszko Anna,Nigam Vishal,Pastuszko Peter The Journal of thoracic and cardiovascular surgery OBJECTIVES:Brain injury, leading to long-term neurodevelopmental deficits, is a major complication in neonates undergoing cardiac surgeries. Because the striatum is one of the most vulnerable brain regions, we used mRNA sequencing to unbiasedly identify transcriptional changes in the striatum after cardiopulmonary bypass and associated deep hypothermic circulatory arrest. METHODS:Piglets were subjected to cardiopulmonary bypass with deep hypothermic circulatory arrest at 18°C for 30 minutes and then recovered for 6 hours. mRNA sequencing was performed to compare changes in gene expression between the striatums of sham control and deep hypothermic circulatory arrest brains. RESULTS:We found 124 significantly upregulated genes and 74 significantly downregulated genes in the striatums of the deep hypothermic circulatory arrest group compared with the sham controls. Pathway enrichment analysis demonstrated that inflammation and apoptosis were the strongest pathways activated after surgery. Chemokines CXCL9, CXCL10, and CCL2 were the top upregulated genes with 32.4-fold, 22.2-fold, and 17.6-fold increased expression, respectively, in the deep hypothermic circulatory arrest group compared with sham controls. Concomitantly, genes involved in cell proliferation, cell-cell adhesion, and structural integrity were significantly downregulated in the deep hypothermic circulatory arrest group. Analysis of promoter regions of all upregulated genes revealed over-representation of nuclear factor-kB transcription factor binding sites. CONCLUSIONS:Our study provides a comprehensive view of global transcriptional changes in the striatum after deep hypothermic circulatory arrest and found strong activation of both inflammatory and apoptotic signaling pathways in the deep hypothermic circulatory arrest group. Nuclear factor-kB, a key driver of inflammation, appears to be an upstream regulator of the majority of the upregulated genes; hence, nuclear factor-kB inhibitors could potentially be tested for beneficial effects on neurologic outcome. 10.1016/j.jtcvs.2019.02.091
    A novel target to reduce microglial inflammation and neuronal damage after deep hypothermic circulatory arrest. Liu Mingyue,Li Yongnan,Gao Sizhe,Yan Shujie,Zhang Qiaoni,Liu Gang,Ji Bingyang The Journal of thoracic and cardiovascular surgery BACKGROUND:Neuroinflammation acts as a contributor to neurologic deficits after deep hypothermic circulatory arrest. However, the molecular mechanism remains unclear. This study postulates that cold-inducible RNA-binding protein can promote deep hypothermic circulatory arrest-induced neuroinflammation. METHODS:Rats were randomly assigned into 3 groups (n = 5, each group): sham group, deep hypothermic circulatory arrest group, and deep hypothermic circulatory arrest + Cirp group (Cirp group). Murine microglial BV2 cells were administered by adeno-associated viral vectors containing cold-inducible RNA-binding protein small interference RNA or negative control small interference RNA at 2 days before 4-hour oxygen-glucose deprivation at 18°C. Microglial activation, cell death, neuroinflammation, and related protein expression were assessed in tissue samples and cell cultures. RESULTS:Cold-inducible RNA-binding protein was elevated along with evident neuroinflammation and neuronal damage in rats exposed to deep hypothermic circulatory arrest. In Cirp rats, histologic injury (3.00 [interquartile range, 2.00-3.00] vs 1.00 [interquartile range, 1.00-1.50] neuropathological score, P < .001) and microglial activation (40 ± 4 vs 13 ± 7 CA1 area, P < .001) were alleviated after deep hypothermic circulatory arrest. With RNA-sequencing analysis, this associated with reduction of key proinflammatory cytokines induced by inhibiting Brd2-NF-κB signals. In BV2 cells treated with small interference RNA-cold-inducible RNA-binding protein, similar protective effects were observed, including decreased proinflammatory cytokines and cytotoxicity. Brd2-NF-κB signals were confirmed by the addition of Brd2 inhibitor JQ1. Notably, the conditioned medium from BV2 cells transfected with small interference RNA cold-inducible RNA-binding protein significantly reduced apoptosis in neural SH-SY5Y cells after oxygen-glucose deprivation, which was similar to that after JQ1 administration. CONCLUSIONS:Enhanced cold-inducible RNA-binding protein in microglia aggravates neuronal injury by promoting the release of proinflammatory cytokines, which might be mediated through Brd2-NF-κB signals during deep hypothermic circulatory arrest. 10.1016/j.jtcvs.2019.06.115
    Inhaled nitric oxide reduces injury and microglia activation in porcine hippocampus after deep hypothermic circulatory arrest. Kajimoto Masaki,Nuri Muhammad,Sleasman Justin R,Charette Kevin A,Nelson Branden R,Portman Michael A The Journal of thoracic and cardiovascular surgery OBJECTIVE:Dysregulation of local nitric oxide (NO) synthetases occurs during ischemia and reperfusion associated with cardiopulmonary bypass, deep hypothermic circulatory arrest (DHCA), and reperfusion. Rapid fluctuations in local NO occurring in neonates and infants probably contribute to inflammation-induced microglial activation and neuronal degeneration after these procedures, eventually impairing neurodevelopment. We evaluated the anti-inflammatory efficacy of inhaled NO (iNO) in a piglet model emulating conditions during pediatric open-heart surgery with DHCA. METHODS:Infant Yorkshire piglets underwent DHCA (18°C) for 30 minutes, followed by reperfusion and rewarming either with or without iNO (20 ppm) in the ventilator at the onset of reperfusion for 3 hours (n = 5 per group, DHCA-iNO and DHCA). Through craniotomy, brains were extracted after perfusion fixation for histology. RESULTS:Plasma NO metabolites were elevated 2.5 times baseline data before DHCA by iNO. Fluoro-Jade C staining identified significantly lower number of degenerating neurons in the hippocampus of the DHCA-iNO group (P = .02) compared with the DHCA group. Morphologic analyses of ionized calcium-binding adapter molecule-1 stained microglia, evaluating cell body and dendritic process geometry with Imaris imaging software, revealed subjectively less microglial activation in the hippocampus of pigs receiving iNO. CONCLUSIONS:Using DHCA for 30 minutes, consistent with clinical exposure, we noted that iNO reduces neuronal degeneration in the hippocampus. In addition, iNO reduces microglial activation in the hippocampus after DHCA. The data suggest that iNO reduces neuronal degeneration by ameliorating inflammation and may be a practical mode of neuroprotection for infants undergoing DHCA. 10.1016/j.jtcvs.2019.12.075
    Effect of Deep Hypothermic Circulatory Arrest Versus Moderate Hypothermic Circulatory Arrest in Aortic Arch Surgery on Postoperative Renal Function: A Systematic Review and Meta-Analysis. Cao Liang,Guo Xiaoxiao,Jia Yuan,Yang Lijing,Wang Hongbai,Yuan Su Journal of the American Heart Association Background Moderate hypothermic circulatory arrest (MHCA) has been widely used in aortic arch surgery. However, the renal function after MHCA remains controversial. We performed a systematic review and meta-analysis direct comparison of the postoperative renal function of MHCA versus deep hypothermic circulatory arrest (DHCA) in aortic arch surgery. Methods and Results We searched PubMed, Embase, and the Cochrane Library for postoperative renal function after aortic arch surgery with using MHCA and DHCA, published from inception to January 31, 2020. The primary outcome was renal failure. Secondary outcomes were the need for renal therapy and other major postoperative outcomes. The random-effects model was used for all comparisons to pool the estimates. A total of 14 observational studies with 4142 patients were included. Compared with DHCA, MHCA significantly reduced the incidence of renal failure (odds ratio [OR], 0.76; 95% CI, 0.61-0.94; =0.011; I=0.0%) and the need of renal replacement (OR, 0.68; 95% CI, 0.48-0.97; =0.034; I=0.0%). Subgroup analysis showed that when the hypothermic circulatory arrest time was <30 minutes, the incidence of renal failure in MHCA group was significantly lower than that in DHCA group (OR, 0.73; 95% CI, 0.54-0.99; =0.040; I=1.1%), whereas an insignificant difference between 2 groups when hypothermic circulatory arrest time was >30 minutes (OR, 0.76; 95% CI, 0.51-1.13; =0.169; I=17.3%). Conclusions MHCA compared with DHCA reduces the incidence of renal failure and the need for renal replacement. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020169348. 10.1161/JAHA.120.017939
    The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest. Kong Minjian,Wei Dongdong,Li Xuebiao,Zhu Xian,Hong Ze,Ni Ming,Wang Yifan,Dong Aiqiang Journal of cellular and molecular medicine Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA-mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3-6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA-mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3-methyladenine (3-MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3-MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA-mediated lung injury. 10.1111/jcmm.17165