Experimental study of oculocardiac reflex (OCR) with graded stimuli.
Khurana Indu,Sharma Rajeev,Khurana A K
Indian journal of physiology and pharmacology
The present study was conducted to observe the effect of graded mechanical stimuli on occurrence of oculocardiac reflex (OCR). The experiments were carried out in twenty albino rabbits of either sex weighing between 1-2 kg. Changes in heart rate and/or cardiac rhythm (oculocardiac reflex) were studied by applying traction with progressively increasing weights to medial rectus muscle. Mean threshold value of square wave mechanical stimulus just sufficient to produce oculocardiac reflex was found to be 19 +/- 8.52 g. As the traction weights were progressively increased, more and more decrease in heart rate was observed. It was concluded that once the threshold value of stimulus was reached, the oculocardiac reflex showed a graded response with progressively increasing traction weights.
Cold face test in the assessment of trigeminal-brainstem-vagal function in humans.
Khurana R K,Watabiki S,Hebel J R,Toro R,Nelson E
Annals of neurology
Study of the reflex heart rate response in humans to apneic facial immersion (simulated diving) and its modifications showed that bradycardia caused by simple application of cold compresses to the face (cold face test) correlated well with that produced by the simulated diving reflex. Bilateral application of cold stimulus to the individual divisions of the trigeminal nerve revealed the ophthalmic division to be the most sensitive pathway for this reflex. The cold face test was standardized in 50 normal individuals and further validated in 10 patients by comparison with the simulated diving reflex, the Valsalva maneuver, and administration of atropine. Patients with diabetes mellitus, brainstem stroke, multiple sclerosis, or Shy-Drager syndrome developed less than normal bradycardia or minimal tachycardia in response to the cold facial stimulus. The cold face test is a novel, simple, safe, and economical test of the integrity of trigeminal-brainstem-vagal reflex pathways, can be utilized practically to assess vagal and brainstem dysfunctions, and has the special advantage of being applicable even in an uncooperative or comatose patient.
10.1002/ana.410070209
The diving reflex used to treat paroxysmal atrial tachycardia.
Wildenthal K,Leshin S J,Atkins J M,Skelton C L
Lancet (London, England)
Induction of the diving reflex, by immersion of the face in cold water (2 degrees C) while the breath was held, converted paroxysmal atrial tachycardia to sinus rhythm within 15-35 seconds in seven patients (aged 22-66). Four had histories of heart attacks that had previously required vasopressor therapy, and two had been digitalised; three had no history of prior paroxysmal atrial tachycardia or heart-disease. The reported procedure, which is convenient, non-invasive, and can be self administered by the patient after brief instruction, may offer a useful adjunct to carotid-sinus massage and intravenous infusion of vasopressors for the treatment of paroxysmal atrial tachycardia.
10.1016/s0140-6736(75)92374-0
Extreme human breath-hold diving.
Ferretti G
European journal of applied physiology
In this paper, the respiratory, circulatory and metabolic adjustments to human extreme breath-hold diving are reviewed. A survey of the literature reveals that in extreme divers, adaptive mechanisms take place that allow prolongation of apnoea beyond the limits attained by non-diving subjects, and preservation of oxygen stores during the dives. The occurrence of a diving response, including peripheral vasoconstriction, increased arterial blood pressure, bradycardia and lowered cardiac output, is strongly implicated. Some peripheral regions may be excluded from perfusion, with consequent reliance on anaerobic metabolism. In addition, extreme breath-hold divers show a blunted ventilatory response to carbon dioxide breathing, possibly as a consequence of frequent exposure to high carbon dioxide partial pressures during the dives. These mechanisms allow the attainment of particularly low alveolar oxygen (< 30 mmHg) and high alveolar carbon dioxide (> 50 mmHg) partial pressures at the end of maximal dry breath-holds, and reduce oxygen consumption during the dive at the expense of increased anaerobic glycolysis (rate of blood lactate accumulation > 0.04 mM.s-1). The current absolute world record for depth in breath-hold diving is 150 m. Its further improvement depends upon how far the equilibrium between starting oxygen stores, the overall rate of energy expenditure, the fraction of energy provided by anaerobic metabolism and the diving speed can be pushed, with consciousness upon emersion. The ultimate limit to breath-hold diving records may indeed be imposed by an energetic constraint.
10.1007/s004210000377
Physiology of static breath holding in elite apneists.
Bain Anthony R,Drvis Ivan,Dujic Zeljko,MacLeod David B,Ainslie Philip N
Experimental physiology
NEW FINDINGS:What is the topic of this review? This review provides an up-to-date assessment of the physiology involved with extreme static dry-land breath holding in trained apneists. What advances does it highlight? We specifically highlight the recent findings involved with the cardiovascular, cerebrovascular and metabolic function during a maximal breath hold in elite apneists. ABSTRACT:Breath-hold-related activities have been performed for centuries, but only recently, within the last ∼30 years, has it emerged as an increasingly popular competitive sport. In apnoea sport, competition relates to underwater distances or simply maximal breath-hold duration, with the current (oxygen-unsupplemented) static breath-hold record at 11 min 35 s. Remarkably, many ultra-elite apneists are able to suppress respiratory urges to the point where consciousness fundamentally limits a breath-hold duration. Here, arterial oxygen saturations as low as ∼50% have been reported. In such cases, oxygen conservation to maintain cerebral functioning is critical, where responses ascribed to the mammalian dive reflex, e.g. sympathetically mediated peripheral vasoconstriction and vagally mediated bradycardia, are central. In defence of maintaining global cerebral oxygen delivery during prolonged breath holds, the cerebral blood flow may increase by ∼100% from resting values. Interestingly, near the termination of prolonged dry static breath holds, recent studies also indicate that reductions in the cerebral oxidative metabolism can occur, probably attributable to the extreme hypercapnia and irrespective of the hypoxaemia. In this review, we highlight and discuss the recent data on the cardiovascular, metabolic and, particularly, cerebrovascular function in competitive apneists performing maximal static breath holds. The physiological adaptation and maladaptation with regular breath-hold training are also summarized, and future research areas in this unique physiological field are highlighted; particularly, the need to determine the potential long-term health impacts of extreme breath holding.
10.1113/EP086269
Animal models for investigating the central control of the Mammalian diving response.
Frontiers in physiology
Pioneering studies by Per Scholander indicated that the diving response consists of reflexly induced apnea, bradycardia and an alteration of blood flow that maintains perfusion of the heart and brain. More recently field physiological studies have shown that many marine animals can adjust cardiorespiratory aspects of their diving response depending upon the behavioral situation. This could suggest that the very labile heart rate during diving is under direct cortical control. However, the final control of autonomic nervous system functioning resides within the brainstem and not the cortex. Many physiologists regard the brain as a "black box" where important neuronal functioning occurs, but the complexity of such functioning leaves systematic investigation a daunting task. As a consequence the central control of the diving response has been under-investigated. Thus, to further advance the field of diving physiology by understanding its central neuronal control, it would be first necessary to understand the reflex circuitry that exists within the brainstem of diving animals. To do this will require an appropriate animal model. In this review, two animals, the muskrat and rat, will be offered as animal models to investigate the central aspects of the diving response. Firstly, although these rodents are not marine animals, natural histories indicate that both animals can and do exploit aquatic environments. Secondly, physiological recordings during natural and simulated diving indicate that both animals possess the same basic physiological responses to underwater submersion that occur in marine animals. Thirdly, the size and ease of housing of both animals makes them attractive laboratory research animals. Finally, the enormous amount of scientific literature regarding rodent brainstem autonomic control mechanisms, and the availability of brain atlases, makes these animals ideal choices to study the central control of the mammalian diving response.
10.3389/fphys.2012.00169
A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.
Johnson Miriam J,Booth Sara,Currow David C,Lam Lawrence T,Phillips Jane L
Journal of pain and symptom management
CONTEXT:The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. OBJECTIVES:To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. METHODS:This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. RESULTS:Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. CONCLUSION:A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study.
10.1016/j.jpainsymman.2015.11.026
Effects of controlled breathing exercises and respiratory muscle training in people with chronic obstructive pulmonary disease: results from evaluating the quality of evidence in systematic reviews.
Borge Christine Råheim,Hagen Kåre Birger,Mengshoel Anne Marit,Omenaas Ernst,Moum Torbjørn,Wahl Astrid Klopstad
BMC pulmonary medicine
BACKGROUND:This paper reviews evidence and quality of Systematic Reviews (SRs) on the effects of breathing control exercises (BCEs) and respiratory muscle training (RMT) on breathlessness/dyspnea and other symptoms, and quality of life (QOL) for individuals with chronic obstructive pulmonary disease (COPD). METHODS:A search for BCE and RMT literature in COPD published between January 1, 2002 and December 31, 2013 was performed in the following databases: PubMed, Ovid, CINAHL, PsycINFO, AMED, Cochrane and PEDro. The AMSTAR criteria were used to evaluate quality. RESULTS:After reviewing 642 reports, seven SRs were identified on RMT and BCEs. Three SRs were of high quality, three were of moderate quality, and one was of low quality. Two high-quality SRs reported significantly beneficial effects of RMT on dyspnea, and one reported significant effects on disease-specific QOL and fatigue. In these SRs, pooled data analyses were performed with three to fourteen single randomised control trials (RCTs) included in the analysis. In one of the SRs the quality of the single RCTs were rated by the authors to be between 5-7 (with10 best) and in the other one the quality of the single RCTs were rated to be between 30-83% of the maximum score.One high-quality SR found a significant positive effect of BCE based on pooled data analysis with two single RCTs in regard to pursed-lip breathing (PLB) on breathlessness. In this SR, one single RCT on diaphragmatic breathing (DB) and another one on yoga breathing (YB) showed effect on disease-specific QOL. The single RCTs included in the SR were rated by the authors in the SRs to be of low and moderate quality. CONCLUSIONS:Based on three high-quality SRs performing pooled data analyses, there is evidence that RMT has effect on breathlessness, fatigue and disease-specific QOL and PLB on breathlessness. There is also evidence that single studies on DB and YB has effect on disease-specific QOL. Few RCTs are available and the variable quality of the single RCTs in the SRs, seem to require more RCTs in particular for BCEs, but also RMT before conclusions regarding effects and high quality SRs can be written.
10.1186/1471-2466-14-184
The Effect of Using an Electric Fan on Dyspnea in Chinese Patients With Terminal Cancer.
Wong Sio Leng,Leong Sok Man,Chan Cheng Man,Kan Sut Peng,Cheng Hon Wai Benjamin
The American journal of hospice & palliative care
BACKGROUND:Fan therapy is often suggested for relieving the symptom of dyspnea in patients with advanced cancer, but relevant literature among Asians is limited. OBJECTIVE:Phase 2 clinical trial to assess the clinical feasibility and outcome of using an electric fan to alleviate the symptom of dyspnea in Chinese patients with advanced cancer. METHODS:Thirty patients with advanced cancer having unresolved breathlessness were recruited from Hospice and Palliative Care Centre of Kiang Wu Hospital in Macau. Participants were randomly and equally allocated to the experimental group and the control group, respectively. OUTCOME MEASURES:Verbal numerical rating scale (NRS) of breathlessness, respiratory rate (RR), and saturation of peripheral oxygen (SpO) was collected before and after the intervention. RESULTS:T test was used to analyze the data collected. There was a significant difference in the NRS scores of the experimental group ( P < .01), indicating a significant reduction in the patients' sensation of breathlessness after fan therapy, whereas no significant difference was found in the objective statistic results of RR and SpO. No significant difference ( P > .05) was found in the control group for all the 3 variables before and after routine treatment. CONCLUSION:The results of the study suggested that fan therapy could be effective in alleviating dyspnea in Chinese patients with advanced cancer. It should be considered as one of the nonpharmacological treatment option. Future large-scale phase 3 clinical trials are warranted.
10.1177/1049909115615127
The importance of the feasibility study: Lessons from a study of the hand-held fan used to relieve dyspnea in people who are breathless at rest.
Booth Sara,Galbraith Sarah,Ryan Richella,Parker Richard A,Johnson Miriam
Palliative medicine
BACKGROUND:The dyspnea accompanying advanced cardiorespiratory disease is often refractory to palliation. It is disabling, distressing and associated with the diseases most common everywhere in the world. The hand-held fan, used to generate a draught across the face, is a simple, cost-effective, safe, and universally applicable palliative breathlessness intervention, consistently described as valuable in qualitative research. A previous crossover trial confirmed its benefit in patients breathless at rest, but the washout period was uncertain. AIM:To determine the washout period after use of the hand-held fan to inform accurate randomized controlled trial design. DESIGN:An observational methodological study. Breathlessness intensity was measured using 100 mm visual analog scale and numerical rating scale, and "relief of breathlessness" was measured on a 5-point scale. Those benefitting from the fan provided visual analog scale/numerical rating scale scores until (1) scores returned to baseline values or (2) until response had plateaued. The primary outcome measure was the time (in minutes) to reach either component of the primary study endpoint. SETTINGS/PARTICIPANTS:Four in-/out-patient hospice/hospital units; participants had chronic refractory breathlessness using the fan. RESULTS:Overall, 31 patients participated (mean age: 74.8 years; range: 49-98 years, standard deviation = 11.5 years); 64% were males. Approximately, half of the sample experienced benefit of moderate effect size. The relative reduction in breathlessness relative to the mean baseline score for the sample was 27% for the visual analog scale and 19% for the numerical rating scale. CONCLUSION:Feasibility work is essential, even for simple widely employed interventions.
10.1177/0269216315607180
Fan Therapy for the Treatment of Dyspnea in Adults: A Systematic Review.
Qian Yu,Wu Yuan,Rozman de Moraes Aline,Yi Xue,Geng Yimin,Dibaj Seyedeh,Liu Diane,Naberhuis Jane,Bruera Eduardo
Journal of pain and symptom management
CONTEXT:The use of a handheld or electric fan has been proposed as one component of the complex clinical interventions used in the relief of dyspnea; however, there is a lack of consensus regarding its efficacy. OBJECTIVES:We performed a systematic review to determine the effectiveness of fan therapy for the treatment of dyspnea. METHODS:We searched the Medline, EMBASE, Web of Science, Scopus, CINAHL, PsycInfo, and Cochrane Library databases to identify all fan therapy studies published from January 1, 1946 to September 31, 2018. The search terms included "dyspnea," "dysponea," "dyspneic," "short of breath," "shortness of breath," "breathless," "breathlessness," "breathing difficulty," "labored breathing," and "fan." Searches were limited to articles in English or Chinese. The bibliographies of identified articles were also manually searched. Three authors independently assessed papers for inclusion. RESULTS:Ten of the 92 unique records identified met the inclusion criteria (nine randomized controlled trials and one cohort study). Most studies (80%) were conducted in the hospital setting, and none were double blinded. Nearly half (159 [46%]) of the 344 total subjects had cancer. The most common nonmalignant disease was chronic obstructive pulmonary disease. The most common duration of fan therapy was five minutes. Six studies (60%) reported a significant improvement in dyspnea with fan therapy. There are two ongoing trials being conducted based on a search of trial registries. CONCLUSION:Limited direct evidence from randomized controlled trials indicates that fan therapy may effectively alleviate dyspnea. Additional trials are warranted to confirm this finding and explore the use of fan therapy for the treatment of dyspnea in more diverse populations and settings.
10.1016/j.jpainsymman.2019.04.011
[Using Fans to Relieve Dyspnea: A Systematic Review and Clinical Implications].
Hu li za zhi The journal of nursing
BACKGROUND:Dyspnea is a subjective symptom of breathing discomfort that is commonly experienced by terminally ill patients in the last few weeks of life. Fans have been used to reduce breathlessness in clinical practice for terminally ill patients. However, reviews in the systematic literature are insufficient to make definite conclusions regarding the effectiveness of this intervention and to provide a consistent protocol for clinical application. PURPOSE:The purpose of the present study was to evaluate the effects and clinical application of using fans in dyspnea patients. METHODS:A systematic review was used. Relevant articles published prior to September 2017 were retrieved from electronic databases including PubMed, CINAHL, MEDLINE, PsycINFO, and Cochrane CENTRAL. Keywords and MeSH terms were identified for each PICO (participant, intervention, comparison, outcome) element, including dyspnea, breathless, breath shortness, breathing difficulty or labored respiration, fan, and scale. A total of 41 articles that matched the search criteria were extracted. After screening the topics, deleting repetitions, and doing critical appraisals, three randomized controlled trials were selected for further analysis. The GRADE (grading of recommendations assessment, development and evaluation) quality of evidence rating was intermediate. RESULTS:The systematic review of the three articles revealed that a fan set at low speed with facial cooling of the 2nd and 3rd branches of the trigeminal nerve as soon as possible for 5 minutes and at a distance that is comfortable for the participant may relieve subjective feelings of dyspnea in nonhypoxic patients (e.g., cardiopulmonary disease and cancer) better than drugs and oxygen treatment alone. CONCLUSIONS / IMPLICATIONS FOR PRACTICE:Reducing the subjective feelings of dyspnea is the first step for nonhypoxic patients. Using a fan to relieve dyspnea is an evidence-based, non-invasive, economical, and effective nonpharmacological palliative intervention.
10.6224/JN.201808_65(4).11
Bilateral sectioning of the anterior ethmoidal nerves does not eliminate the diving response in voluntarily diving rats.
Chotiyanonta Jill S,Dinovo Karyn M,McCulloch Paul F
Physiological reports
The diving response is characterized by bradycardia, apnea, and increased peripheral resistance. This reflex response is initiated by immersing the nose in water. Because the anterior ethmoidal nerve (AEN) innervates the nose, our hypothesis was that intact AENs are essential for initiating the diving response in voluntarily diving rats. Heart rate (HR) and arterial blood pressure (BPa) were monitored using implanted biotransmitters. Sprague-Dawley rats were trained to voluntarily swim 5 m underwater. During diving, HR decreased from 480 ± 15 to 99 ± 5 bpm and BPa increased from 136 ± 2 to 187 ± 3 mmHg. Experimental rats (N = 9) then received bilateral AEN sectioning, while Sham rats (N = 8) did not. During diving in Experimental rats 7 days after AEN surgery, HR decreased from 478 ± 13 to 76 ± 4 bpm and BPa increased from 134 ± 3 to 186 ± 4 mmHg. Responses were similar in Sham rats. Then, during nasal stimulation with ammonia vapors in urethane-anesthetized Experimental rats, HR decreased from 368 ± 7 to 83 ± 4 bpm, and BPa increased from 126 ± 7 to 175 ± 4 mmHg. Responses were similar in Sham rats. Thus, 1 week after being sectioned the AENs are not essential for initiating a full cardiorespiratory response during both voluntary diving and nasal stimulation. We conclude that other nerve(s) innervating the nose are able to provide an afferent signal sufficient to initiate the diving response, although neuronal plasticity within the medullary dorsal horn may be necessary for this to occur.
10.1002/phy2.141
The rat: a laboratory model for studies of the diving response.
Panneton W Michael,Gan Qi,Juric Rajko
Journal of applied physiology (Bethesda, Md. : 1985)
Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily "dunked" underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control.
10.1152/japplphysiol.00600.2009
Innervation of the Nose and Nasal Region of the Rat: Implications for Initiating the Mammalian Diving Response.
McCulloch Paul F,Lahrman Kenneth A,DelPrete Benjamin,DiNovo Karyn M
Frontiers in neuroanatomy
Most terrestrial animals demonstrate an autonomic reflex that facilitates survival during prolonged submersion under water. This diving response is characterized by bradycardia, apnea and selective increases in peripheral vascular resistance. Stimulation of the nose and nasal passages is thought to be primarily responsible for providing the sensory afferent signals initiating this protective reflex. Consequently, the primary objective of this research was to determine the central terminal projections of nerves innervating the external nose, nasal vestibule and nasal passages of rats. We injected wheat germ agglutinin (WGA) into specific external nasal locations, into the internal nasal passages of rats both with and without intact anterior ethmoidal nerves (AENs), and directly into trigeminal nerves innervating the nose and nasal region. The central terminations of these projections within the medulla were then precisely mapped. Results indicate that the internal nasal branch of the AEN and the nasopalatine nerve, but not the infraorbital nerve (ION), provide primary innervation of the internal nasal passages. The results also suggest afferent fibers from the internal nasal passages, but not external nasal region, project to the medullary dorsal horn (MDH) in an appropriate anatomical way to cause the activation of secondary neurons within the ventral MDH that express Fos protein during diving. We conclude that innervation of the anterior nasal passages by the AEN and nasopalatine nerve is likely to provide the afferent information responsible for the activation of secondary neurons within MDH during voluntary diving in rats.
10.3389/fnana.2018.00085
Diving bradycardia: a mechanism of defence against hypoxic damage.
Alboni Paolo,Alboni Marco,Gianfranchi Lorella
Journal of cardiovascular medicine (Hagerstown, Md.)
A feature of all air-breathing vertebrates, diving bradycardia is triggered by apnoea and accentuated by immersion of the face or whole body in cold water. Very little is known about the afferents of diving bradycardia, whereas the efferent part of the reflex circuit is constituted by the cardiac vagal fibres. Diving bradycardia is associated with vasoconstriction of selected vascular beds and a reduction in cardiac output. The diving response appears to be more pronounced in mammals than in birds. In humans, the bradycardic response to diving varies greatly from person to person; the reduction in heart rate generally ranges from 15 to 40%, but a small proportion of healthy individuals can develop bradycardia below 20 beats/min. During prolonged dives, bradycardia becomes more pronounced because of activation of the peripheral chemoreceptors by a reduction in the arterial partial pressure of oxygen (O2), responsible for slowing of heart rate. The vasoconstriction is associated with a redistribution of the blood flow, which saves O2 for the O2-sensitive organs, such as the heart and brain. The results of several investigations carried out both in animals and in humans show that the diving response has an O2-conserving effect, both during exercise and at rest, thus lengthening the time to the onset of serious hypoxic damage. The diving response can therefore be regarded as an important defence mechanism for the organism.
10.2459/JCM.0b013e328344bcdc
Is V̇O suppressed during nonapnoeic facial submersion?
Anderson Sarah,Chamberlain Maggie R,Musgrove Samantha,Partusch Antonia,Tice Keagan R J,Thorp David B
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
The mammalian dive response (DR) is described as oxygen-conserving based on measures of bradycardia, peripheral vasoconstriction, and decreased ventilation (V̇). Using a model of simulated diving, this study examined the effect of nonapnoeic facial submersions (NAFS) on oxygen consumption (V̇O). 19 participants performed four 2-min NAFS with 8 min of rest between each. Two submersions were performed in 5 °C water, 2 in 25 °C water. Heart rate (HR) was collected using chest strap monitors. A tube connected to the inspired port of a non-rebreathing valve allowed participants to breathe during facial submersion. Expired air was directed to a metabolic cart to determine V̇O and V̇. Baseline (BL) HR, V̇O, and V̇ values were determined by the average during the 2 min prior to facial submersion; cold shock response (CSR) values were the maximum during the first 30 s of facial submersion; and NAFS values were the minimum during the last 90 s of facial submersion. A 2-way repeated-measures ANOVA indicated that both HR and V̇ were greater during the CSR (92.5 ± 3.6 beats/min, 16.3 ± 0.8 L/min) compared with BL (78.9 ± 3.2 beats/min, 8.7 ± 0.4 L/min), while both were decreased from BL during the NAFS (60.0 ± 4.0 beats/min, 6.0 ± 0.4 L/min) (all, p < 0.05). HR was higher and HR lower in 5 °C versus 25 °C water (p < 0.05), while V̇ was greater in 5 °C conditions (p < 0.05). V̇O exceeded BL during the CSR and decreased below BL during the NAFS (BL: 5.3 ± 0.1, CSR: 9.8 ± 0.4, NAFS: 3.1 ± 0.2 mL·kg·min, p < 0.05). The data illustrate that NAFS alone contributes to the oxygen conservation associated with the human DR.
10.1139/apnm-2016-0268
Repetitive Diving in Trained Rats Still Increases Fos Production in Brainstem Neurons after Bilateral Sectioning of the Anterior Ethmoidal Nerve.
McCulloch Paul F,Warren Erik A,DiNovo Karyn M
Frontiers in physiology
This research was designed to investigate the role of the anterior ethmoidal nerve (AEN) during repetitive trained diving in rats, with specific attention to activation of afferent and efferent brainstem nuclei that are part of this reflexive response. The AEN innervates the nose and nasal passages and is thought to be an important component of the afferent limb of the diving response. Male Sprague-Dawley rats (N = 24) were trained to swim and dive through a 5 m underwater maze. Some rats (N = 12) had bilateral sectioning of the AEN, others a Sham surgery (N = 12). Twelve rats (6 AEN cut and 6 Sham) had 24 post-surgical dive trials over 2 h to activate brainstem neurons to produce Fos, a neuronal activation marker. Remaining rats were non-diving controls. Diving animals had significantly more Fos-positive neurons than non-diving animals in the caudal pressor area, ventral medullary dorsal horn, ventral paratrigeminal nucleus, nucleus tractus solitarius, rostral ventrolateral medulla, Raphe nuclei, A5, Locus Coeruleus, and Kölliker-Fuse area. There were no significant differences in brainstem Fos labeling in rats diving with and without intact AENs. Thus, the AENs are not required for initiation of the diving response. Other nerve(s) that innervate the nose and nasal passages, and/or suprabulbar activation of brainstem neurons, may be responsible for the pattern of neuronal activation observed during repetitive trained diving in rats. These results help define the central neuronal circuitry of the mammalian diving response.
10.3389/fphys.2016.00148
Exercise at depth alters bradycardia and incidence of cardiac anomalies in deep-diving marine mammals.
Williams Terrie M,Fuiman Lee A,Kendall Traci,Berry Patrick,Richter Beau,Noren Shawn R,Thometz Nicole,Shattock Michael J,Farrell Edward,Stamper Andy M,Davis Randall W
Nature communications
Unlike their terrestrial ancestors, marine mammals routinely confront extreme physiological and physical challenges while breath-holding and pursuing prey at depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we deployed animal-borne instruments that recorded high-resolution electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the surface to >200 m. Here we report that both exercise and depth alter the bradycardia associated with the dive response, with the greatest impacts at depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in >73% of deep, aerobic dives, which we attribute to the interplay between sympathetic and parasympathetic drivers for exercise and diving, respectively. Such marked cardiac variability alters the common view of a stereotypic 'dive reflex' in diving mammals. It also suggests the persistence of ancestral terrestrial traits in cardiac function that may help explain the unique sensitivity of some deep-diving marine mammals to anthropogenic disturbances.
10.1038/ncomms7055
Trigeminal cardiac reflex: new thinking model about the definition based on a literature review.
Meuwly C,Golanov E,Chowdhury T,Erne P,Schaller B
Medicine
Trigeminocardiac reflex (TCR) is a brainstem reflex that manifests as sudden onset of hemodynamic perturbation in blood pressure (MABP) and heart rate (HR), as apnea and as gastric hypermotility during stimulation of any branches of the trigeminal nerve. The molecular and clinical knowledge about the TCR is in a constant growth since 1999, what implies a current need of a review about its definition in this changing context. Relevant literature was identified through searching in PubMed (MEDLINE) and Google scholar database for the terms TCR, oculocardiac reflex, diving reflex, vasovagale response. The definition of the TCR varies in clinical as well as in research studies. The main difference applies the required change of MABP and sometimes also HR, which most varies between 10% and 20%. Due to this definition problem, we defined, related to actual literature, 2 major (plausibility, reversibility) and 2 minor criteria (repetition, prevention) for a more proper identification of the TCR in a clinical or research setting. Latest research implies that there is a need for a more extended classification with 2 additional subgroups, considering also the diving reflex and the brainstem reflex. In this review, we highlighted criteria for proper definition and classification of the TCR in the light of increased knowledge and present a thinking model to overcome this complexity. Further we separately discussed the role of HR and MABP and their variation in this context. As another subtopic we gave attention to is the chronic TCR; a variant that is rarely seen in clinical medicine.
10.1097/MD.0000000000000484
Training rats to voluntarily dive underwater: investigations of the mammalian diving response.
McCulloch Paul F
Journal of visualized experiments : JoVE
Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.
10.3791/52093
Sleep Disorders: Is the Trigemino-Cardiac Reflex a Missing Link?
Chowdhury Tumul,Bindu Barkha,Singh Gyaninder Pal,Schaller Bernhard
Frontiers in neurology
Trigeminal innervated areas in face, nasolacrimal, and nasal mucosa can produce a wide array of cardiorespiratory manifestations that include apnea, bradypnea, bradycardia, hypotension, and arrhythmias. This reflex is a well-known entity called "trigemino-cardiac reflex" (TCR). The role of TCR is investigated in various pathophysiological conditions especially in neurosurgical, but also skull base surgery procedures. Additionally, its significance in various sleep-related disorders has also been highlighted recently. Though, the role of diving reflex, a subtype of TCR, has been extensively investigated in sudden infant death syndrome. The data related to other sleep disorders including obstructive sleep apnea, bruxism is very limited and thus, this mini review aims to investigate the possible role and correlation of TCR in causing such sleep abnormalities.
10.3389/fneur.2017.00063
[The function of the heart changes in implementation of the diving reactions in humans].
Baranova T I,Berlov D N,Zavarina L B,Minigalin A D,Smith N Y,Xu S,Yanvareva I N
Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova
The changes of chronotropic function of the heart and of the myocardium in the implementation of the diving response in humans were studied by the electrocardiographic method. The study involved 80 students aged 18-20 years. Diving simulation was performed by immersing the face in cold water during breath-hold exhale. When the water temperature was 12.3 +/- 2.3 degrees C, average duration of apnea was 31 +/- 11 s. The oxygen content in the exhaled air after apnea was 98.8 +/- 8.7 mm Hg, carbon dioxide--49.1 +/- 3.5 mm Hg. It was observed slowing of the heart rate, mainly due to the increasing of diastole in 41 of the 80 surveyed during simulating diving. But it also can be observed symptoms of conduction deterioration: atrioventricular block type I (22% of reactive type and 29% of the highly reactive type subjects), and exceeds standards QTc-interval prolongation (at 7.5% of the subjects). These responses are adaptive in nature and disappear in the recovery process. But the fact abnormalities of conduction in the myocardium must be considered when using the diving reflex in medical practice, as may be due to a predisposition to a certain pathology of the cardiovascular system.
Medical Management and Risk Reduction of the Cardiovascular Effects of Underwater Diving.
Whayne Thomas F
Current vascular pharmacology
Undersea diving is a sport and commercial industry. Knowledge of potential problems began with Caisson disease or "the bends", first identified with compressed air in the construction of tunnels under rivers in the 19th century. Subsequently, there was the commercially used old-fashioned diving helmet attached to a suit, with compressed air pumped down from the surface. Breathhold diving, with no supplementary source of air or other breathing mixture, is also a sport as well as a commercial fishing tool in some parts of the world. There has been an evolution to self-contained underwater breathing apparatus (SCUBA) diving with major involvement as a recreational sport but also of major commercial importance. Knowledge of the physiology and cardiovascular plus other medical problems associated with the various forms of diving have evolved extensively. The major medical catastrophes of SCUBA diving are air embolism and decompression sickness (DCS). Understanding of the essential referral to a hyperbaric recompression chamber for these problems is critical, as well as immediate measures until that recompression is achieved. These include the administration of 100% oxygen and rehydration with intravenous normal saline. Undersea diving continues to expand, especially as a sport, and a basic understanding of the associated preventive and emergency medicine will decrease complications and save lives.
10.2174/1570161115666170621084316
Cardiovascular response to trigeminal nerve stimulation at rest and during exercise in humans: does sex matter?
Prodel Eliza,Barbosa Thales C,Nóbrega Antonio C,Vianna Lauro C
American journal of physiology. Regulatory, integrative and comparative physiology
We sought to investigate the possibility that there are sex differences in the cardiovascular responses to trigeminal nerve stimulation (TGS) with cold exposure to the face at rest and during dynamic exercise. In 9 healthy men (age: 28 ± 3 yr; height: 178 ± 1 cm; weight: 77 ± 8 kg) and 13 women (age 26 ± 5 yr; height 164 ± 3 cm; weight 63 ± 7 kg) beat-to-beat heart rate (HR) and blood pressure were recorded. Mean arterial pressure (MAP), stroke volume (SV), cardiac index (CI), and total vascular resistance index (TVRI) were calculated. TGS was applied for 3 min at rest and in-between 10-min steady-state cycling exercise at a HR of 110 beats/min, the measurements were obtained during the last minute of each period. At rest, TGS increased MAP (men: Δ18 ± 8 mmHg; women: Δ23 ± 8 mmHg; means ± SD), TVRI (men: Δ1.1 ± 0.6 mmHg·l·min·m; women: Δ1.2 ± 1.2 mmHg·l·min·m) and SV (men: Δ19 ± 15 ml; women: Δ16 ± 11 ml) in both groups. CI increased with TGS in women but not in men. However, men presented a bradycardic response to TGS (Δ-11 ± 8 beats/min) that was not significant in women compared with baseline. Cycling exercise increased HR, MAP, SV, and CI and decreased TVRI in men and women. TGS during exercise further increased MAP in men and women and did not change CI in either group. SV and TVRI increased with TGS during exercise only in women. TGS during exercise evoked bradycardia in men (Δ-7 ± 9 beats/min), whereas HR was unchanged in women. Our findings indicate sex differences in TGS-related cardiovascular responses at rest and during exercise.
10.1152/ajpregu.00406.2017
Trigeminal Cardiac Reflex and Cerebral Blood Flow Regulation.
Lapi Dominga,Scuri Rossana,Colantuoni Antonio
Frontiers in neuroscience
The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals). During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart, and brain and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is sequestered within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing. The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min) by jaw extension in rats produces interesting effects both at systemic and cerebral levels, reducing the arterial blood pressure, and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activate the nitric oxide release by vascular endothelial cells. Therefore, the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension. Opposite effects, such as hypotension, and modulation of cerebral arteriolar tone, were observed, when these responses were compared to those elicited by the diving reflex.
10.3389/fnins.2016.00470
The mammalian diving response: an enigmatic reflex to preserve life?
Panneton W Michael
Physiology (Bethesda, Md.)
The mammalian diving response is a remarkable behavior that overrides basic homeostatic reflexes. It is most studied in large aquatic mammals but is seen in all vertebrates. Pelagic mammals have developed several physiological adaptations to conserve intrinsic oxygen stores, but the apnea, bradycardia, and vasoconstriction is shared with those terrestrial and is neurally mediated. The adaptations of aquatic mammals are reviewed here as well as the neural control of cardiorespiratory physiology during diving in rodents.
10.1152/physiol.00020.2013
Sympathetic nerve activity and simulated diving in healthy humans.
Shamsuzzaman Abu,Ackerman Michael J,Kuniyoshi Fatima Sert,Accurso Valentina,Davison Diane,Amin Raouf S,Somers Virend K
Autonomic neuroscience : basic & clinical
The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.
10.1016/j.autneu.2013.12.001
The oxygen-conserving potential of the diving response: A kinetic-based analysis.
Costalat Guillaume,Coquart Jeremy,Castres Ingrid,Joulia Fabrice,Sirost Olivier,Clua Eric,Lemaître Frédéric
Journal of sports sciences
We investigated the oxygen-conserving potential of the human diving response by comparing trained breath-hold divers (BHDs) to non-divers (NDs) during simulated dynamic breath-holding (BH). Changes in haemodynamics [heart rate (HR), stroke volume (SV), cardiac output (CO)] and peripheral muscle oxygenation [oxyhaemoglobin ([HbO]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), tissue saturation index (TSI)] and peripheral oxygen saturation (SpO) were continuously recorded during simulated dynamic BH. BHDs showed a breaking point in HR kinetics at mid-BH immediately preceding a more pronounced drop in HR (-0.86 bpm.%) while HR kinetics in NDs steadily decreased throughout BH (-0.47 bpm.%). By contrast, SV remained unchanged during BH in both groups (all P > 0.05). Near-infrared spectroscopy (NIRS) results (mean ± SD) expressed as percentage changes from the initial values showed a lower [HHb] increase for BHDs than for NDs at the cessation of BH (+24.0 ± 10.1 vs. +39.2 ± 9.6%, respectively; P < 0.05). As a result, BHDs showed a [tHb] drop that NDs did not at the end of BH (-7.3 ± 3.2 vs. -3.0 ± 4.7%, respectively; P < 0.05). The most striking finding of the present study was that BHDs presented an increase in oxygen-conserving efficiency due to substantial shifts in both cardiac and peripheral haemodynamics during simulated BH. In addition, the kinetic-based approach we used provides further credence to the concept of an "oxygen-conserving breaking point" in the human diving response.
10.1080/02640414.2016.1183809
Diving and exercise: the interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans.
Fisher James P,Fernandes Igor A,Barbosa Thales C,Prodel Eliza,Coote John H,Nóbrega Antonio Claudio L,Vianna Lauro C
American journal of physiology. Heart and circulatory physiology
Swimming involves muscular activity and submersion, creating a conflict of autonomic reflexes elicited by the trigeminal receptors and skeletal muscle afferents. We sought to determine the autonomic cardiovascular responses to separate and concurrent stimulation of the trigeminal cutaneous receptors and metabolically sensitive skeletal muscle afferents (muscle metaboreflex). In eight healthy men (30 ± 2 yr) muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), femoral artery blood flow (duplex Doppler ultrasonography), and femoral vascular conductance (femoral artery blood flow/MAP) were assessed during the following three experimental conditions: 1) facial cooling (trigeminal nerve stimulation), 2) postexercise ischemia (PEI; muscle metaboreflex activation) following isometric handgrip, and 3) trigeminal nerve stimulation with concurrent PEI. Trigeminal nerve stimulation produced significant increases in MSNA total activity (Δ347 ± 167%) and MAP (Δ21 ± 5%) and a reduction in femoral artery vascular conductance (Δ-17 ± 9%). PEI also evoked significant increases in MSNA total activity (Δ234 ± 83%) and MAP (Δ36 ± 4%) and a slight nonsignificant reduction in femoral artery vascular conductance (Δ-9 ± 12%). Trigeminal nerve stimulation with concurrent PEI evoked changes in MSNA total activity (Δ341 ± 96%), MAP (Δ39 ± 4%), and femoral artery vascular conductance (Δ-20 ± 9%) that were similar to those evoked by either separate trigeminal nerve stimulation or separate PEI. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not summate algebraically in eliciting a MSNA and cardiovascular response but rather exhibit synaptic occlusion, suggesting a high degree of convergent inputs on output neurons.
10.1152/ajpheart.00728.2014
[Complex profile of the reflex diving response].
Wierzba Tomasz H,Ropiak Arkadiusz
Kardiologia polska
Breath-holding coupled with face cooling triggers a set of the reflex cardiovascular responses, defined as a diving reflex. The major reflex responses include a decrease in heart rate and peripheral vasoconstriction with an increase of arterial pressure to evoke central blood pooling with preferential provision of the brain and heart perfusion. Due to high individual variability and situational dependence the individual course of the reflex response is hardly predictable. Heart rhythm disturbances are the major, sometimes fatal complications of the response. This review is an outline of causing factors, circumstances, mechanisms and the effects of the diving reflex and their practical implications, including risk factors of the critical arrhythmias occurred in diving.
Diving into the Ice Bucket Challenge: Intraparenchymal Hemorrhage and the Mammalian Diving Reflex.
McKee Kathleen,Nelson Sarah,Batra Ayush,Klein Joshua P,Henderson Galen V
The Neurohospitalist
Triggered by facial exposure to cold water and apnea, the mammalian diving reflex consists of bradycardia and peripheral arteriolar vasoconstriction leading to an increase in central arterial pressure. It has been previously associated with ischemic stroke but not definitively with intracerebral hemorrhage. We present a case of intracerebral hemorrhage occurring in a woman with poorly controlled hypertension following her participation in the amyotrophic lateral sclerosis fund-raising "Ice Bucket Challenge," in which ice-cold water was poured on her head. We suspect that facial exposure to ice-cold water triggered the diving reflex, causing a hypertensive surge and ultimately the intracerebral hemorrhage.
10.1177/1941874415573024
The trigeminocardiac reflex - a comparison with the diving reflex in humans.
Lemaitre Frederic,Chowdhury Tumul,Schaller Bernhard
Archives of medical science : AMS
The trigeminocardiac reflex (TCR) has previously been described in the literature as a reflexive response of bradycardia, hypotension, and gastric hypermotility seen upon mechanical stimulation in the distribution of the trigeminal nerve. The diving reflex (DR) in humans is characterized by breath-holding, slowing of the heart rate, reduction of limb blood flow and a gradual rise in the mean arterial blood pressure. Although the two reflexes share many similarities, their relationship and especially their functional purpose in humans have yet to be fully elucidated. In the present review, we have tried to integrate and elaborate these two phenomena into a unified physiological concept. Assuming that the TCR and the DR are closely linked functionally and phylogenetically, we have also highlighted the significance of these reflexes in humans.
10.5114/aoms.2015.50974
Using stimulation of the diving reflex in humans to teach integrative physiology.
Choate Julia K,Denton Kate M,Evans Roger G,Hodgson Yvonne
Advances in physiology education
During underwater submersion, the body responds by conserving O2 and prioritizing blood flow to the brain and heart. These physiological adjustments, which involve the nervous, cardiovascular, and respiratory systems, are known as the diving response and provide an ideal example of integrative physiology. The diving reflex can be stimulated in the practical laboratory setting using breath holding and facial immersion in water. Our undergraduate physiology students complete a laboratory class in which they investigate the effects of stimulating the diving reflex on cardiovascular variables, which are recorded and calculated with a Finapres finger cuff. These variables include heart rate, cardiac output, stroke volume, total peripheral resistance, and arterial pressures (mean, diastolic, and systolic). Components of the diving reflex are stimulated by 1) facial immersion in cold water (15°C), 2) breathing with a snorkel in cold water (15°C), 3) facial immersion in warm water (30°C), and 4) breath holding in air. Statistical analysis of the data generated for each of these four maneuvers allows the students to consider the factors that contribute to the diving response, such as the temperature of the water and the location of the sensory receptors that initiate the response. In addition to providing specific details about the equipment, protocols, and learning outcomes, this report describes how we assess this practical exercise and summarizes some common student misunderstandings of the essential physiological concepts underlying the diving response.
10.1152/advan.00125.2013