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  • 1. Further studies on perfusion of isolated frog's heart with modified Ringer solutions (glucose-Ringer, maltose-Ringer and lactose-Ringer).
    作者:Bhargava R P , Variyar M C , Sharma K S , Tuteja K S
    期刊:Indian journal of physiology and pharmacology
    日期:1964-10-01
  • 2. CHANGES OF THE PERMEABILITY OF THE ISOLATED FROG HEART IRRADIATED WITH X RAYS. PROTECTIVE ACTION OF GLUCOSE, OF CYSTEAMINE AND OF SODIUM THIOSULPHATE.
    作者:MILLO A , DEBENEDETTI A
    期刊:Rivista di biologia
    日期:1964-01-01
  • 3. Use of frog ventricle to examine mechanical and electrical activity of heart.
    作者:Knight V A , Richardson D R , Makoba B
    期刊:The American journal of physiology
    日期:1989-06-01
    DOI :10.1152/advances.1989.256.6.S9
    This report describes a Langendorff heart preparation, which utilizes frog rather than mammalian hearts to demonstrate both mechanical and electrical events of the cardiac cycle. The preparation is durable in that it can be maintained for several hours while being perfused with room-temperature solutions that are not supplemented with oxygen. Ventricular perfusion is achieved via a fluid-filled reservoir coupled to a truncus arteriosus catheter advanced into the ventricle. By varying the height of the reservoir relative to the heart, changes in ventricular pressure and the rate of ventricular pressure change during systole can be recorded by way of a side port on the catheter tubing. The former is indicative of Starling's law of the heart, whereas the latter is reflective of the contractility. Electrical activity of the heart can be observed by measuring injury potentials via a needle electrode inserted into the ventricle. These are extracellular potentials that reflect ventricular action potentials. In addition, surface electrodes placed on the ventricle can be used to detect an integrated ventricular electrocardiogram. Recording of ventricular pressure simultaneously with at least one of these two electrical recordings allows a direct comparison of electrical and mechanical events of the heart. In summary, the Langendorff frog heart preparation is economical in terms of both financial cost and simplicity; yet it enables a thorough examination of both electrical and mechanical properties of the heart either as a student lab exercise or as a classroom demonstration.
  • 3区Q1影响因子: 3
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    4. Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells.
    期刊:Transplant international : official journal of the European Society for Organ Transplantation
    日期:2024-01-18
    DOI :10.3389/ti.2024.11900
    The generation of insulin-producing cells from human-induced pluripotent stem cells holds great potential for diabetes modeling and treatment. However, existing protocols typically involve incubating cells with un-physiologically high concentrations of glucose, which often fail to generate fully functional IPCs. Here, we investigated the influence of high (20 mM) versus low (5.5 mM) glucose concentrations on IPCs differentiation in three hiPSC lines. In two hiPSC lines that were unable to differentiate to IPCs sufficiently, we found that high glucose during differentiation leads to a shortage of NKX6.1+ cells that have co-expression with PDX1 due to insufficient gene activation, thus further reducing differentiation efficiency. Furthermore, high glucose during differentiation weakened mitochondrial respiration ability. In the third iPSC line, which is IPC differentiation amenable, glucose concentrations did not affect the / expression and differentiation efficiency. In addition, glucose-stimulated insulin secretion was only seen in the differentiation under a high glucose condition. These IPCs have higher KATP channel activity and were linked to sufficient gene expression under a high glucose condition. These data suggest high glucose concentration during IPC differentiation is necessary to generate functional IPCs. However, in cell lines that were IPC differentiation unamenable, high glucose could worsen the situation.
  • 1区Q1影响因子: 8.9
    5. Glucose affects the severity of hypoxic-ischemic brain injury in newborn pigs.
    作者:LeBlanc M H , Huang M , Vig V , Patel D , Smith E E
    期刊:Stroke
    日期:1993-07-01
    BACKGROUND AND PURPOSE:The administration of glucose has been shown to worsen brain injury in adult animals but has no effect on the severity of injury in newborn rats. We wished to see whether the results in newborn rats could be extended to another newborn animal. METHODS:In 44 0- to 3-day-old piglets, hypoxic-ischemic central nervous system damage was induced by ligation of both carotid arteries and reduction of their blood pressure to two-thirds normal for one-half hour. In the last 15 minutes of this half hour, oxygen concentration was reduced to 6%. The piglets were randomized to receive either 2 mL/kg 50% dextrose in water followed by 2 mL/kg per hour for 2.5 hours beginning before ischemia or enough insulin to reduce their resting blood sugar to approximately 2 mmol/L. RESULTS:Neurological exam scores in the glucose-treated piglets at 1 day after injury were significantly worse than those in the insulin-treated group. Pathological examination scores were poorer in the glucose-treated group (13.6 +/- 1.9 [mean +/- SEM]) than in the insulin-treated group (24.7 +/- 1.4, P < .01). CONCLUSIONS:Increasing serum glucose during hypoxic-ischemic injury to the newborn piglet's brain worsens brain injury.
  • 2区Q1影响因子: 4.4
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    6. Factors affecting the supply of glucose to the heart of the rat, in vivo.
    作者:Daniel P M , Love E R , Pratt O E
    期刊:The Journal of physiology
    日期:1980-12-01
    DOI :10.1113/jphysiol.1980.sp013501
    1. The influx of glucose into the heart of intact, living, anaesthetized rats was measured when the levels of insulin the blood were (a) low (as a result of fasting), (b) normal, and (c) high (as a result of injecting insulin). The findings showed that the transport of glucose into cardiac cells is carrier-mediated and is strongly insulin-independent. 2. The major barrier to the supply glucose to the heart from the circulating blood is at the surface membrane of the cardiac cells, rather than at the endothelium of the cardiac capillaries. 3. The extracellular space of the heart was measured and was found to be approximately 25% of the cardiac tissue. 4. During life, glucose, as well as its analogue, 3-O-methylglucose passes across the membranes of the cells of the heart by means of a transport system which is strongly dependent upon insulin and appears to be carried-mediated. A likely explanation for the effect of insulin is that it increases considerably the affinity of the transport carrier for glucose. Saturation of the carrier takes place when the levels of insulin and of glucose in the blood are high. However, when the concentration of insulin is low, e.g. during a fast, the affinity of the carrier for glucose is reduced so that saturation cannot be demonstrated. 5. It is suggested that the low level of insulin that is found in the blood in the early morning, which is due to the night fast, may lead to the cardiac dysfunction which often develops at that time.
  • 3区Q2影响因子: 3.7
    7. The role of calcium in the regulation of glucose uptake in isolated working rat heart.
    作者:Zechner Christoph , Beyersdorf Friedhelm , Doenst Torsten
    期刊:Molecular and cellular biochemistry
    日期:2002-03-01
    Catecholamines or ischemia may increase myocardial glucose uptake by an increase in intracellular calcium. We tested the hypothesis that increasing or decreasing extracellular calcium supply would change glucose uptake. Hearts were perfused for 60 min at a physiological workload with Krebs-Henseleit buffer containing glucose (5 mM) and oleate (0.4 mM; bound to 1% BSA). Calcium concentration was 2.5 mM. In group A (control; n = 12), insulin (1 mU/ml) was added at 30 min. In Group B (n = 7), the calcium concentration was increased to 5.0 and 7.5 mM at 20 min and 40 min, respectively. In Group C (n = 7), verapamil was added at 20 min (0.25 microM) and 40 min (1.0 microM) to decrease calcium influx. In group D (n = 7), EDTA was added at 20 min (0.5 mM) and at 40 min (1.5 mM) to decrease the free extracellular calcium. Glucose uptake was measured by 3H2O production from [2-3H]glucose and cardiac work was measured simultaneously. Cardiac power in group B was 8.24 +/- 0.60 mW at 2.5 mM calcium, 9.45 +/- 0.50 mW at 5 mM calcium and 7.99 +/- 0.99 mW at 7.5 mM calcium (n.s.). The addition of verapamil decreased contractile function in a dose-dependent manner (8.50 +/- 0.74 vs. 3.11 +/- 0.84 vs. 1.48 +/- 0.39 mW, p < 0.01) suggesting that verapamil decreased cytosolic calcium concentration. A similar dose-dependent reduction in contractile performance was observed in the EDTA group (8.44 +/- 0.81 vs. 7.42 +/- 0.96 vs. 4.03 +/- 1.32 mW, p < 0.01). Glucose uptake was 1.35 +/- 0.11 micromol/min/g dry weight under control conditions. Glucose uptake increased threefold with the addition of insulin. Increasing extracellular [Ca2+] did not affect glucose uptake. Decreasing Ca2+ availability showed a trend towards a decrease in glucose uptake (n.s.), which was minor compared to the decrease in contractile function. We conclude that extracellular calcium does not regulate glucose uptake in the isolated working rat heart in the presence of glucose and fatty acids as substrates. The trend of decreased glucose uptake when calcium supply was limited may be due to dramatically reduced energy demand and not directly due to changes in calcium.
  • 2区Q1影响因子: 4.4
    8. The optimal glucose concentration for intermittent cardioplegia in isolated rat heart when added to St. Thomas' Hospital cardioplegic solution.
    作者:Owen P , du Toit E F , Opie L H
    期刊:The Journal of thoracic and cardiovascular surgery
    日期:1993-06-01
    The purpose of this study was to determine the mechanisms by which high physiologic concentrations of glucose (11 mmol/L) were protective while even higher concentrations (20 or 50 mmol/L) were harmful when added to St. Thomas' Hospital No. 2 cardioplegic solution. We evaluated the recovery of isolated working rat hearts subjected to 3 hours of hypothermic multidose cardioplegic arrest. The addition of glucose 11 mmol/L was associated with better aortic flow (79.2% +/- 1.3%) than the addition of glucose 1 mmol/L (61.7% +/- 2.7%), 20 mmol/L (73.6% +/- 1.1%), or 50 mmol/L (66.0% +/- 3.2%) (p < 0.01 versus glucose 1 and 50 mmol/L). An increase in glucose concentration from 1 to 50 mmol/L progressively augmented glucose flux from 2.2 +/- 0.33 to 10.4 +/- 0.79 mumol/gm per 3 hours (p < 0.01), but higher glucose concentrations of 20 and 50 mmol/L inhibited glycogenolysis (p < 0.05 versus glucose 1 and 11 mmol/L), so that total glycolysis was decreased and consequently glycolytic adenosine triphosphate production was reduced from 35.9 +/- 0.47 (glucose 11 mmol/L) to 27.5 +/- 1.25 mumol/gm per 3 hours (glucose 50 mmol/L) (p < 0.01). The end products of glycolysis (lactate and protons) did not appear to affect the recovery of the hearts, because both lactate efflux and tissue lactate were highest in the presence of glucose 11 mmol/L and the pH of the cardioplegic effluent was more alkalotic in glucose 11 and 20 mmol/L. Thus a high physiologic concentration of glucose (11 mmol/L) in the cardioplegic solution improved recovery because of an increased glycolytic adenosine triphosphate production during cardioplegic arrest, whereas even higher concentrations of glucose inhibited these effects.
  • 1区Q1影响因子: 10.6
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    9. Evidence that tirzepatide protects against diabetes-related cardiac damages.
    期刊:Cardiovascular diabetology
    日期:2024-03-30
    DOI :10.1186/s12933-024-02203-4
    BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. METHODS:A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. RESULTS:Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r = 0.01, I = 23.45%, H = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. CONCLUSION:Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.
  • 3区Q1影响因子: 2.5
    10. The impact of diabetic glucose concentration on viability and cardiac differentiation of mesenchymal stem cells.
    期刊:Tissue & cell
    日期:2024-03-16
    DOI :10.1016/j.tice.2024.102361
    INTRODUCTION:Hyperglycemia may be a stumbling block for delivery of regenerative benefits of mesenchymal stem cells (MSCs) to diabetic patients with cardiovascular diseases. Our study aims to assess the viability and cardiac differentiation potential of MSCs after being exposed to diabetic glucose concentration. METHODS:MSCs were extracted from rat bone marrow. Cells were characterized based on morphology, differentiation potential, and expression of mesenchymal specific markers. MTT assay was done to evaluate the viability of MSCs after treatment with different glucose concentrations. Case group was MSCs treated with diabetic concentration of glucose versus cells treated with PBS as the control group. Growth curve and population doubling time were calculated in both groups. Expression of GATA4 and troponin, as the early and late markers during cardiac differentiation, were measured following 5-azacytidine exposure. RESULTS:Proliferated cells at passage three had fibroblastic-shape, was able to differentiate into adipocytes or osteocytes, and expressed CD73 and CD90. MSCs viability was gradually decreased by increasing glucose concentration. Irrespective of nicotine concentration, three-day exposure imposed more severe detrimental effects on viability compared with one-day treatment. Proliferation rate of the MSCs was lower in the case group, and they need more time for population doubling. Expression of both cardiac markers were downregulated in the case group at day three. However, their expression became higher at day seven. CONCLUSION:Diabetic glucose concentration inhibits normal proliferation and cardiac differentiation of MSCs. This effect should be considered in stem cell therapy of cardiovascular patients who are concurrently affected by hyperglycemia, a common comorbidity in such individuals. Why carry out this study? What was learned from the study? FINDINGS:
  • 2区Q1影响因子: 4.7
    11. A study of the effects of substrates on intracellular pH in toad ventricular strips.
    作者:Snow T R
    期刊:Journal of molecular and cellular cardiology
    日期:1986-07-01
    The ability of different substrates to affect myocardial function is well established but the mechanism for this effect has yet to be determined. To explore this area further, the studies described below were designed to determine the effect of different metabolic substrates, glucose or pyruvate, on myocardial response to hypercapnia. To assess this response, both the mechanical performance and the intracellular pH (pHi) were continuously measured. Intracellular pH was measured using the changes in absorbance of the vital staining dye, neutral red (NR). Although the presence of either substrate did not affect the response to hypercapnia, the addition of pyruvate was accompanied by a significant change in pHi. Specifically, there was a monotonic decrease in pHi comparable to that observed when PCO2 is increased from 5% to 10% (delta OD = -0.018 +/- 0.002 CO2; delta OD = -0.020 +/- 0.002 PYR, respectively). The mechanical response was similar for both; developed tension (tau) decreased initially (97 +/- 6% v. 93 +/- 8%) and then recovered (115 +/- 4% v. 101% +/- 5%). However, the changes in the maximum rate of relaxation, i.e. minimum time derivative: (tau mn) were dependent on the cause of the decrease in pHi. With hypercapnia, tau mn initially decreased and this was followed by a recovery phase which was 147 +/- 8% of the initial value. With pyruvate, tau mn decreased to 81 +/- 5% of control and was followed by no recovery. Because of the difference in the changes in tau mn, the effects of theophylline [3, 5] on these responses were determined. There was no effect on the response to an increase in PCO2. However, with theophylline present, the addition of pyruvate was accompanied by an increase in pHi (delta OD = + 0.005 +/- 0.001). The mechanical response was consistent with this increase and was similar to that seen when PCO2 is decreased from 10% to 5%. Specifically, there was an increase in tau (122 +/- 7%) followed by a small decrease (113 +/- 4%). Tissue assays for lactate showed a significant increase with the introduction of pyruvate. However, this increase was not affected by the presence of theophylline despite the opposite response of pHi. The data suggest that pyruvate affects myocardial function by altering pHi, and this effect is not due to an increase in lactate. In addition, the data are consistent with the model that the heart is capable of accommodating changes in pHi with only transient effects on contractile function.
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