scholarly journals An integrated comparative physiology and molecular approach pinpoints mediators of breath-hold capacity in dolphins

2021 ◽  
Author(s):  
Ashley M. Blawas ◽  
Kathryn E. Ware ◽  
Emma Schmaltz ◽  
Jake Spruance ◽  
Austin S. Allen ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Marine Mammals ◽  
Ischemia Reperfusion ◽  
Hypoxia Tolerance ◽  
Breath Holding ◽  
Breath Hold ◽  
Rna Seq ◽  
Molecular Features ◽  
Ischemic Events ◽  
Ischemic Stress

AbstractIschemic events, such as ischemic heart disease and ischemic stroke, are the number one cause of death globally. Ischemia prevents blood, carrying essential nutrients and oxygen, from reaching the tissues leading to cell death, tissue death, and eventual organ failure. While humans are relatively intolerant to these ischemic events, other species, such as marine mammals, have evolved remarkable tolerance to chronic ischemia/reperfusion during diving. Here we capitalized on the unique adaptations of bottlenose dolphins (Tursiops truncatus) as a comparative model of ischemic stress and hypoxia tolerance to identify molecular features associated with breath-holding. Using RNA-Seq we observed time-dependent upregulation of the arachidonate 5-lipoxygenase (ALOX5) gene during breath-holding. Consistent with the RNA-Seq data, we also observed increased ALOX5 enzymatic activity in the serum of dolphins undergoing breath-holds. ALOX5 has previously been shown to be activated during hypoxia in rodent models, and its metabolites, leukotrienes, induce vasoconstriction. The upregulation of ALOX5 occurred within the estimated aerobic dive limit of the species, suggesting that ALOX5 enzymatic activity may promote tolerance to ischemic stress through sustained vasoconstriction in dolphins during diving. These observations pinpoint a potential molecular mechanism by which dolphins, and perhaps other marine mammals, have adapted to the prolonged breath-holds associated with diving.

The diving physiology of bottlenose dolphins (Tursiops truncatus). I. Balancing the demands of exercise for energy conservation at depth

1999 ◽  
Vol 202 (20) ◽  
pp. 2739-2748 ◽  
Author(s):  
T.M. Williams ◽  
J.E. Haun ◽  
W.A. Friedl
Keyword(s):  
Heart Rate ◽  
Blood Lactate ◽  
Tursiops Truncatus ◽  
Marine Mammals ◽  
Bottlenose Dolphins ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Energetic Cost ◽  
Breath Holding ◽  
Breath Hold

During diving, marine mammals must rely on the efficient utilization of a limited oxygen reserve sequestered in the lungs, blood and muscles. To determine the effects of exercise and apnea on the use of these reserves, we examined the physiological responses of adult bottlenose dolphins (Tursiops truncatus) trained to breath-hold on the water surface or to dive to submerged targets at depths between 60 and 210 m. Changes in blood lactate levels, in partial pressures of oxygen and carbon dioxide and in heart rate were assessed while the dolphins performed sedentary breath-holds. The effects of exercise on breath-hold capacity were examined by measuring heart rate and post-dive respiration rate and blood lactate concentration for dolphins diving in Kaneohe Bay, Oahu, Hawaii. Ascent and descent rates, stroke frequency and swimming patterns were monitored during the dives. The results showed that lactate concentration was 1.1+/−0.1 mmol l(−1) at rest and increased non-linearly with the duration of the sedentary breath-hold or dive. Lactate concentration was consistently higher for the diving animals at all comparable periods of apnea. Breakpoints in plots of lactate concentration and blood gas levels against breath-hold duration (P(O2), P(CO2)) for sedentary breath-holding dolphins occurred between 200 and 240 s. In comparison, the calculated aerobic dive limit for adult dolphins was 268 s. Descent and ascent rates ranged from 1.5 to 2.5 m s(−1) during 210 m dives and were often outside the predicted range for swimming at low energetic cost. Rather than constant propulsion, diving dolphins used interrupted modes of swimming, with more than 75 % of the final ascent spent gliding. Physiological and behavioral measurements from this study indicate that superimposing swimming exercise on apnea was energetically costly for the diving dolphin but was circumvented in part by modifying the mode of swimming.

scholarly journals Diving deep: understanding the genetic components of hypoxia tolerance in marine mammals

2020 ◽  
Vol 128 (5) ◽  
pp. 1439-1446
Author(s):  
Allyson G. Hindle
Keyword(s):  
Marine Mammal ◽  
Marine Mammals ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Deep Understanding ◽  
Hypoxia Tolerance ◽  
Breath Holding ◽  
Oxygen Binding ◽  
Cell Protection ◽  
Genetic Components

Marine mammals have highly specialized physiology, exhibited in many species by extreme breath-holding capabilities that allow deep dives and extended submergence. Cardiovascular control and cell-level hypoxia tolerance are key features of this phenotype. Identifying genomic signatures tied to physiology will be valuable in understanding these natural model species, which may generate translational opportunities to human diseases arising from hypoxic stress or tissue injury. Genomic analyses have now been conducted in dolphins, river dolphins, minke whales, bowhead whales, and polar bears, with multispecies studies exploring evolutionary signals across marine mammal lineages, encompassing extinct and extant divers. Single-species genome studies for sirenians do not yet exist. Extant marine mammals arose in three lineages from separate aquatic recolonizations. Their physiological specializations, along with these independent origins create an interesting case to examine convergent evolution. Although molecular mechanisms of hypoxia tolerance are not universally apparent across marine mammal genomic studies, altered evolutionary rates have been identified for genes linked to oxygen binding and transport (e.g., MB, HBA, and HBB), blood pressure control (e.g., endothelin pathway genes), and cell protection in multiple species. Despite convergent phenotypes across clades, instances of identical molecular convergence have been uncommon. Given the inherent logistical and regulatory difficulties associated with functional genetic experiments in marine mammals, several avenues of further investigation are suggested to enable validation of candidate genes for hypoxia tolerance: leveraging phylogeny to better understand convergent phenotypes; ontogenic studies to identify regulation of key genes underlying the elite, adult, hypoxia-tolerant physiology; and cell culture manipulations to understand gene function.

Hypoxia Tolerance, Nitric Oxide, and Nitrite: Lessons From Extreme Animals

Physiology ◽  
2015 ◽  
Vol 30 (2) ◽  
pp. 116-126 ◽  
Author(s):  
Angela Fago ◽  
Frank B. Jensen
Keyword(s):  
Nitric Oxide ◽  
Marine Mammals ◽  
Crucian Carp ◽  
Physiological Responses ◽  
Oxygen Deprivation ◽  
Hypoxia Tolerance ◽  
Carassius Carassius ◽  
Slider Turtle ◽  
Total Lack ◽  
Crucian Carp Carassius Carassius

Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles ( Chrysemys picta and Trachemys scripta) and the crucian carp ( Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and–in air-breathing animals–redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals.

scholarly journals Comparison of Compressed Sensing and Gradient and Spin-Echo in Breath-Hold 3D MR Cholangiopancreatography: Qualitative and Quantitative Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 634
Author(s):  
Weon Jang ◽  
Ji Soo Song ◽  
Sang Heon Kim ◽  
Jae Do Yang
Keyword(s):  
Image Quality ◽  
Compressed Sensing ◽  
Spin Echo ◽  
Contrast Ratio ◽  
Rank Test ◽  
Breath Holding ◽  
Breath Hold ◽  
Background Suppression ◽  
Time Saving ◽  
Noise Ratio

While magnetic resonance cholangiopancreatography (MRCP) is routinely used, compressed sensing MRCP (CS-MRCP) and gradient and spin-echo MRCP (GRASE-MRCP) with breath-holding (BH) may allow sufficient image quality with shorter acquisition times. This study qualitatively and quantitatively compared BH-CS-MRCP and BH-GRASE-MRCP and evaluated their clinical effectiveness. Data from 59 consecutive patients who underwent both BH-CS-MRCP and BH-GRASE-MRCP were qualitatively analyzed using a five-point Likert-type scale. The signal-to-noise ratio (SNR) of the common bile duct (CBD), contrast-to-noise ratio (CNR) of the CBD and liver, and contrast ratio between periductal tissue and the CBD were measured. Paired t-test, Wilcoxon signed-rank test, and McNemar’s test were used for statistical analysis. No significant differences were found in overall image quality or duct visualization of the CBD, right and left 1st level intrahepatic duct (IHD), cystic duct, and proximal pancreatic duct (PD). BH-CS-MRCP demonstrated higher background suppression and better visualization of right (p = 0.004) and left 2nd level IHD (p < 0.001), mid PD (p = 0.003), and distal PD (p = 0.041). Image quality degradation was less with BH-GRASE-MRCP than BH-CS-MRCP (p = 0.025). Of 24 patients with communication between a cyst and the PD, 21 (87.5%) and 15 patients (62.5%) demonstrated such communication on BH-CS-MRCP and BH-GRASE-MRCP, respectively. SNR, contrast ratio, and CNR of BH-CS-MRCP were higher than BH-GRASE-MRCP (p < 0.001). Both BH-CS-MRCP and BH-GRASE-MRCP are useful imaging methods with sufficient image quality. Each method has advantages, such as better visualization of small ducts with BH-CS-MRCP and greater time saving with BH-GRASE-MRCP. These differences allow diverse choices for visualization of the pancreaticobiliary tree in clinical practice.

Metabolic adjustments to breath holding in higher vertebrates

1989 ◽  
Vol 67 (12) ◽  
pp. 3024-3031 ◽  
Author(s):  
P. J. Butler
Keyword(s):  
Marine Mammals ◽  
Lactate Production ◽  
Weddell Seal ◽  
Specific Dynamic Action ◽  
The Body ◽  
Breath Holding ◽  
Reduced Body ◽  
Key Factor ◽  
Reduced Rate ◽  
Anaerobic Production

There is substantial behavioural and physiological evidence to suggest that most feeding dives by aquatic birds and mammals are aerobic in nature, with no net production of lactate. Any increase in lactate production is matched by increased removal. This does not mean, however, that there are no cardiovascular adjustments associated with such dives. Nonactive parts of the body (including the large pectoral muscles in diving ducks) may be hypoperfused and consume oxygen at a reduced rate. For example, in marine mammals, such as the Weddell seal, reduced perfusion of the gut during a feeding period (which can last for up to 12 h) would reduce the energy expenditure associated with the digestion and assimilation of food (specific dynamic action). Reperfusion during the nonfeeding period would contribute to an unusually high "resting" oxygen uptake. Although some tissues in seals at least can tolerate periods of ischaemia, there is no evidence to suggest that enhanced anaerobic production of ATP is a key factor in the survival of marine mammals during unusually long periods underwater. There may, in fact, be an overall reduction in the ATP requirements of certain tissues, possibly as a result of a reduction in the permeability of cell membranes to some ions, but most certainly as a result of reduced body temperature. During relatively long dives, lactate production eventually exceeds its rate of removal and it accumulates. Precisely what occurs in the muscles is not known. One suggestion is that periods of vasoconstriction are interrupted by vasodilatation, when the oxygen stores are replaced.

Effect of lung volume on breath holding

1987 ◽  
Vol 62 (5) ◽  
pp. 1962-1969 ◽  
Author(s):  
W. A. Whitelaw ◽  
B. McBride ◽  
G. T. Ford
Keyword(s):  
Lung Volume ◽  
Hold Time ◽  
Esophageal Pressure ◽  
Breath Holding ◽  
Breath Hold ◽  
Pressure Waves ◽  
Expiratory Muscle ◽  
Inspiratory Muscles ◽  
Consistent Change ◽  
Rhythmic Contractions

The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2–92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding.

scholarly journals Effect of gravity on aerosol dispersion and deposition in the human lung after periods of breath holding

2000 ◽  
Vol 89 (5) ◽  
pp. 1787-1792 ◽  
Author(s):  
Chantal Darquenne ◽  
Manuel Paiva ◽  
G. Kim Prisk
Keyword(s):  
Flow Rate ◽  
Turbulent Mixing ◽  
Direct Evidence ◽  
Human Lung ◽  
Hold Time ◽  
Aerosol Deposition ◽  
Breath Holding ◽  
Breath Hold ◽  
Constant Flow Rate ◽  
Aerosol Dispersion

To determine the extent of the role that gravity plays in dispersion and deposition during breath holds, we performed aerosol bolus inhalations of 1-μm-diameter particles followed by breath holds of various lengths on four subjects on the ground (1G) and during short periods of microgravity (μG). Boluses of ∼70 ml were inhaled to penetration volumes (Vp) of 150 and 500 ml, at a constant flow rate of ∼0.45 l/s. Aerosol concentration and flow rate were continuously measured at the mouth. Aerosol deposition and dispersion were calculated from these data. Deposition was independent of breath-hold time at both Vp in μG, whereas, in 1G, deposition increased with increasing breath hold time. At Vp = 150 ml, dispersion was similar at both gravity levels and increased with breath hold time. At Vp = 500 ml, dispersion in 1G was always significantly higher than in μG. The data provide direct evidence that gravitational sedimentation is the main mechanism of deposition and dispersion during breath holds. The data also suggest that cardiogenic mixing and turbulent mixing contribute to deposition and dispersion at shallow Vp.

Changing effect of lung volume on respiratory drive in man

1975 ◽  
Vol 38 (5) ◽  
pp. 768-773 ◽  
Author(s):  
N. N. Stanley ◽  
M. D. Altose ◽  
S. G. Kelsen ◽  
C. F. Ward ◽  
N. S. Cherniack
Keyword(s):  
Human Subjects ◽  
Inhibitory Effect ◽  
Breath Holding ◽  
Breath Hold ◽  
Respiratory Drive ◽  
Lung Inflation ◽  
Single Breath ◽  
Single Breath Hold ◽  
Sustained Effect ◽  
Residual Capacity

Experiments were conducted on human subjects to study the effect of lung inflation during breath holding on respiratory drive. Two series of experiments were performed: the first to examine respiratory drive during a single breath hold, the second designed to examine the sustained effect of lung inflation on subsequent breath holds. The experiments involved breath holding begun either at the end of a normal expiration or after a maximum inspiration. When breath holding was repeated at 10-min intervals, the increase in BHT produced by lung inflation was greater in short breath holds (after CO2 rebreathing) than in long breath holds (after hyperventilation). If breath holds were made in rapid succession, the first breath hold was much longer when made at total lung capacity than at functional residual capacity, but this effect of lung inflation diminished in subsequent breath holds. It is concluded that the inhibitory effect of lung inflation decays during breath holding and is regained remarkably slowly during the period of breathing immediately after breath holding.

Control of ventilation in elite synchronized swimmers

1987 ◽  
Vol 63 (3) ◽  
pp. 1019-1024 ◽  
Author(s):  
R. L. Bjurstrom ◽  
R. B. Schoene
Keyword(s):  
Heart Rate ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Mean Value ◽  
Heart Rate Change ◽  
Breath Holding ◽  
Breath Hold ◽  
Lung Volumes ◽  
Co2 Partial Pressure ◽  
Control Of Ventilation

Synchronized swimmers perform strenuous underwater exercise during prolonged breath holds. To investigate the role of the control of ventilation and lung volumes in these athletes, we studied the 10 members of the National Synchronized Swim Team including an olympic gold medalist and 10 age-matched controls. We evaluated static pulmonary function, hypoxic and hypercapnic ventilatory drives, and normoxic and hyperoxic breath holding. Synchronized swimmers had an increased total lung capacity and vital capacity compared with controls (P less than 0.005). The hypoxic ventilatory response (expressed as the hyperbolic shape parameter A) was lower in the synchronized swimmers than controls with a mean value of 29.2 +/- 2.6 (SE) and 65.6 +/- 7.1, respectively (P less than 0.001). The hypercapnic ventilatory response [expressed as S, minute ventilation (1/min)/alveolar CO2 partial pressure (Torr)] was no different between synchronized swimmers and controls. Breath-hold duration during normoxia was greater in the synchronized swimmers, with a mean value of 108.6 +/- 4.8 (SE) vs. 68.03 +/- 8.1 s in the controls (P less than 0.001). No difference was seen in hyperoxic breath-hold times between groups. During breath holding synchronized swimmers demonstrated marked apneic bradycardia expressed as either absolute or heart rate change from basal heart rate as opposed to the controls, in whom heart rate increased during breath holds. Therefore the results show that elite synchronized swimmers have increased lung volumes, blunted hypoxic ventilatory responses, and a marked apneic bradycardia that may provide physiological characteristics that offer a competitive advantage for championship performance.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1587
Author(s):  
Syed Kashif Zaidi ◽  
Farid Ahmed ◽  
Heba Alkhatabi ◽  
Md Nasrul Hoda ◽  
Muhammad Al-Qahtani
Keyword(s):  
Brain Tissue ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Behavioral Outcomes ◽  
Reperfusion Therapy ◽  
Brain Tissue Oxygenation ◽  
Effective Interventions ◽  
Stroke Models ◽  
Field Therapy ◽  
Ischemic Events

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of “clinically” relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, “IV-effects” of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 μg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.

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