Pulmonary ventilation-perfusion mismatch: a novel hypothesis for how diving vertebrates may avoid the bends.

Hydrostatic lung compression in diving marine mammals, with collapsing alveoli blocking gas exchange at depth, has been the main theoretical basis for limiting N2 uptake and avoiding gas emboli (GE) as they ascend. However, studies of beached and bycaught cetaceans and sea turtles imply that air-breathing marine vertebrates may, under unusual circumstances, develop GE that result in decompression sickness (DCS) symptoms. Theoretical modelling of tissue and blood gas dynamics of breath-hold divers suggests that changes in perfusion and blood flow distribution may also play a significant role. The results from the modelling work suggest that our current understanding of diving physiology in many species is poor, as the models predict blood and tissue N2 levels that would result in severe DCS symptoms (chokes, paralysis and death) in a large fraction of natural dive profiles. In this review, we combine published results from marine mammals and turtles to propose alternative mechanisms for how marine vertebrates control gas exchange in the lung, through management of the pulmonary distribution of alveolar ventilation ([Formula: see text]) and cardiac output/lung perfusion ([Formula: see text]), varying the level of [Formula: see text] in different regions of the lung. Man-made disturbances, causing stress, could alter the [Formula: see text] mismatch level in the lung, resulting in an abnormally elevated uptake of N2, increasing the risk for GE. Our hypothesis provides avenues for new areas of research, offers an explanation for how sonar exposure may alter physiology causing GE and provides a new mechanism for how air-breathing marine vertebrates usually avoid the diving-related problems observed in human divers.

Decompression sickness ('the bends') in sea turtles.

Decompression sickness (DCS), as clinically diagnosed by reversal of symptoms with recompression, has never been reported in aquatic breath-hold diving vertebrates despite the occurrence of tissue gas tensions sufficient for bubble formation and injury in terrestrial animals. Similarly to diving mammals, sea turtles manage gas exchange and decompression through anatomical, physiological, and behavioral adaptations. In the former group, DCS-like lesions have been observed on necropsies following behavioral disturbance such as high-powered acoustic sources (e.g. active sonar) and in bycaught animals. In sea turtles, in spite of abundant literature on diving physiology and bycatch interference, this is the first report of DCS-like symptoms and lesions. We diagnosed a clinico-pathological condition consistent with DCS in 29 gas-embolized loggerhead sea turtles Caretta caretta from a sample of 67. Fifty-nine were recovered alive and 8 had recently died following bycatch in trawls and gillnets of local fisheries from the east coast of Spain. Gas embolization and distribution in vital organs were evaluated through conventional radiography, computed tomography, and ultrasound. Additionally, positive response following repressurization was clinically observed in 2 live affected turtles. Gas embolism was also observed postmortem in carcasses and tissues as described in cetaceans and human divers. Compositional gas analysis of intravascular bubbles was consistent with DCS. Definitive diagnosis of DCS in sea turtles opens a new era for research in sea turtle diving physiology, conservation, and bycatch impact mitigation, as well as for comparative studies in other air-breathing marine vertebrates and human divers.

On how whales avoid decompression sickness and why they sometimes strand.

Whales are unique in that the supply of blood to the brain is not by the internal carotid arteries, but by way of thoracic and intra-vertebral arterial retia. We found in the harbor porpoise (Phocoena phocoena) that these retia split up into smaller anastomosing vessels and thin-walled sinusoid structures that are embedded in fat. The solubility of nitrogen is at least six times larger in fat than in water, and we suggest that nitrogen in supersaturated blood will be absorbed in the fat, by diffusion, during the very slow passage of the blood through the arterial retia. Formation of nitrogen bubbles that may reach the brain is thereby avoided. We also suggest that mass stranding of whales may be due to disturbances to their normal dive profiles, resulting in extra release of nitrogen that may overburden the nitrogen 'trap' and allow bubbles to reach the brain and cause abnormal behavior.

Bubbles in live-stranded dolphins.

Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber-muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.

Evidence of injury caused by gas bubbles in a live marine mammal: barotrauma in a California sea lion Zalophus californianus.

A yearling male California sea lion Zalophus californianus with hypermetric ataxia and bilateral negative menace reflexes was brought to The Marine Mammal Center, Sausalito, California, U.S.A., in late 2009 for medical assessment and treatment. The clinical signs were due to multiple gas bubbles within the cerebellum. These lesions were intraparenchymal, multifocal to coalescing, spherical to ovoid, and varied from 0.5 to 2.4 cm diameter. The gas composed 21.3% of the total cerebellum volume. Three rib fractures were also noted during diagnostic evaluation and were presumed to be associated with the gas bubbles in the brain. The progression of clinical signs and lesion appearance were monitored with magnetic resonance imaging, cognitive function testing and computed tomography. Gas filled voids in the cerebellum were filled with fluid on follow up images. Clinical signs resolved and the sea lion was released with a satellite tag attached. Post release the animal travelled approximately 75 km north and 80 km south of the release site and the tag recorded dives of over 150 m depth. The animal re-stranded 25 d following release and died of a subacute bronchopneumonia and pleuritis. This is the first instance of clinical injury due to gas bubble formation described in a living pinniped and the first sea lion with quantifiable cerebellar damage to take part in spatial learning and memory testing.

Could beaked whales get the bends? Effect of diving behaviour and physiology on modelled gas exchange for three species: Ziphius cavirostris, Mesoplodon densirostris and Hyperoodon ampullatus.

A mathematical model, based on current knowledge of gas exchange and physiology of marine mammals, was used to predict blood and tissue tension N2 (P(N2)) using field data from three beaked whale species: northern bottlenose whales, Cuvier's beaked whales, and Blainville's beaked whales. The objective was to determine if physiology (body mass, diving lung volume, dive response) or dive behaviour (dive depth and duration, changes in ascent rate, diel behaviour) would lead to differences in P(N2) levels and thereby decompression sickness (DCS) risk between species. Diving lung volume and extent of the dive response had a large effect on end-dive P(N2). The dive profile had a larger influence on end-dive P(N2) than body mass differences between species. Despite diel changes in dive behaviour, P(N2) levels showed no consistent trend. Model output suggested that all three species live with tissue P(N2) levels that would cause a significant proportion of DCS cases in terrestrial mammals. Cuvier's beaked whale diving behaviour appears to put them at higher risk than the other species, which may explain their prevalence in strandings after the use of mid-frequency sonar.

Decompression syndrome and the evolution of deep diving physiology in the Cetacea.

Whales repetitively dive deep to feed and should be susceptible to decompression syndrome, though they are not known to suffer the associated pathologies. Avascular osteonecrosis has been recognized as an indicator of diving habits of extinct marine amniotes. Vertebrae of 331 individual modern and 996 fossil whales were subjected to macroscopic and radiographic examination. Avascular osteonecrosis was found in the Oligocene basal odontocetes (Xenorophoidea) and in geologically younger mysticetes, such as Aglaocetus [a sister taxon to Balaenopteridae + (Balaenidae + Eschrichtiidae) clade]. These are considered as early "experiments" in repetitive deep diving, indicating that they independently converged on their similar specialized diving physiologies.

To what extent might N2 limit dive performance in king penguins?

A mathematical model was used to explore if elevated levels of N2, and risk of decompression sickness (DCS), could limit dive performance (duration and depth) in king penguins (Aptenodytes patagonicus). The model allowed prediction of blood and tissue (central circulation, muscle, brain and fat) N2 tensions (P(N2)) based on different cardiac outputs and blood flow distributions. Estimated mixed venous P(N2) agreed with values observed during forced dives in a compression chamber used to validate the assumptions of the model. During bouts of foraging dives, estimated mixed venous and tissue P(N2) increased as the bout progressed. Estimated mean maximum mixed venous P(N2) upon return to the surface after a dive was 4.56+/-0.18 atmospheres absolute (ATA; range: 4.37-4.78 ATA). This is equivalent to N2 levels causing a 50% DCS incidence in terrestrial animals of similar mass. Bout termination events were not associated with extreme mixed venous N2 levels. Fat P(N2) was positively correlated with bout duration and the highest estimated fat P(N2) occurred at the end of a dive bout. The model suggested that short and shallow dives occurring between dive bouts help to reduce supersaturation and thereby DCS risk. Furthermore, adipose tissue could also help reduce DCS risk during the first few dives in a bout by functioning as a sink to buffer extreme levels of N2.

"Gas and fat embolic syndrome" involving a mass stranding of beaked whales (family Ziphiidae) exposed to anthropogenic sonar signals.

A study of the lesions of beaked whales (BWs) in a recent mass stranding in the Canary Islands following naval exercises provides a possible explanation of the relationship between anthropogenic, acoustic (sonar) activities and the stranding and death of marine mammals. Fourteen BWs were stranded in the Canary Islands close to the site of an international naval exercise (Neo-Tapon 2002) held on 24 September 2002. Strandings began about 4 hours after the onset of midfrequency sonar activity. Eight Cuvier's BWs (Ziphius cavirostris), one Blainville's BW (Mesoplodon densirostris), and one Gervais' BW (Mesoplodon europaeus) were examined postmortem and studied histopathologically. No inflammatory or neoplastic processes were noted, and no pathogens were identified. Macroscopically, whales had severe, diffuse congestion and hemorrhage, especially around the acoustic jaw fat, ears, brain, and kidneys. Gas bubble-associated lesions and fat embolism were observed in the vessels and parenchyma of vital organs. In vivo bubble formation associated with sonar exposure that may have been exacerbated by modified diving behavior caused nitrogen supersaturation above a threshold value normally tolerated by the tissues (as occurs in decompression sickness). Alternatively, the effect that sonar has on tissues that have been supersaturated with nitrogen gas could be such that it lowers the threshold for the expansion of in vivo bubble precursors (gas nuclei). Exclusively or in combination, these mechanisms may enhance and maintain bubble growth or initiate embolism. Severely injured whales died or became stranded and died due to cardiovascular collapse during beaching. The present study demonstrates a new pathologic entity in cetaceans. The syndrome is apparently induced by exposure to mid-frequency sonar signals and particularly affects deep, long-duration, repetitive-diving species like BWs.

Acute and chronic gas bubble lesions in cetaceans stranded in the United Kingdom.

The first evidence suggestive of in vivo gas bubble formation in cetacea, including eight animals stranded in the UK, has recently been reported. This article presents the pathologic findings from these eight UK-stranded cetaceans and two additional UK-stranded cetacean cases in detail. Hepatic gas-filled cavitary lesions (0.2-6.0 cm diameter) involving approximately 5-90% of the liver volume were found in four (two juvenile, two adult) Risso's dolphins (Grampus griseus), three (two adult, one juvenile) common dolphins (Delphinus delphis), an adult Blainville's beaked whale (Mesoplodon densirostris), and an adult harbour porpoise (Phocoena phocoena). Histopathologic examination of the seven dolphin cases with gross liver cavities revealed variable degrees of pericavitary fibrosis, microscopic, intrahepatic, spherical, nonstaining cavities (typically 50-750 microm in diameter) consistent with gas emboli within distended portal vessels and sinusoids and associated with hepatic tissue compression, hemorrhages, fibrin/organizing thrombi, and foci of acute hepato-cellular necrosis. Two common dolphins also had multiple and bilateral gross renal cavities (2.0-9.0 mm diameter) that, microscopically, were consistent with acute (n = 2) and chronic (n = 1) arterial gas emboli-induced renal infarcts. Microscopic, bubblelike cavities were also found in mesenteric lymph node (n = 4), adrenal (n = 2), spleen (n = 2), pulmonary associated lymph node (n = 1), posterior cervical lymph node (n = 1), and thyroid (n = 1). No bacterial organisms were isolated from five of six cavitated livers and one of one cavitated kidneys. The etiology and pathogenesis of these lesions are not known, although a decompression-related mechanism involving embolism of intestinal gas or de novo gas bubble (emboli) development derived from tissues supersaturated with nitrogen is suspected.

Cumulative sperm whale bone damage and the bends.

Diving mosasaurs, plesiosaurs, and humans develop dysbaric osteonecrosis from end-artery nitrogen embolism ("the bends") in certain bones. Sixteen sperm whales from calves to large adults showed a size-related development of osteonecrosis in chevron and rib bone articulations, deltoid crests, and nasal bones. Occurrence in animals from the Pacific and Atlantic oceans over 111 years made a pathophysiological diagnosis of dysbarism most likely. Decompression avoidance therefore may constrain diving behavior. This suggests why some deep-diving mammals show periodic shallow-depth activity and why gas emboli are found in animals driven to surface precipitously by acoustic stressors such as mid-frequency sonar systems.

Pathology: whales, sonar and decompression sickness.

We do not yet know why whales occasionally strand after sonar has been deployed nearby, but such information is important for both naval undersea activities and the protection of marine mammals. Jepson et al. suggest that a peculiar gas-forming disease afflicting some stranded cetaceans could be a type of decompression sickness (DCS) resulting from exposure to mid-range sonar. However, neither decompression theory nor observation support the existence of a naturally occurring DCS in whales that is characterized by encapsulated, gas-filled cavities in the liver. Although gas-bubble formation may be aggravated by acoustic energy, more rigorous investigation is needed before sonar can be firmly linked to bubble formation in whales.

Acute neurologic decompression illness in pigs: lesions of the spinal cord and brain.

A detailed histopathologic description of central nervous system lesions from a porcine model of neurologic decompression illness is presented. Pigs were dived in a dry chamber to 200 feet of seawater for 24 min before the start of decompression. Of 120 pigs, 40 (33.3%) were functionally unaffected and 80 (66.6%) developed neurologic decompression illness; 16 died, 64 survived. Petechial hemorrhages were grossly visible in the spinal cord of 73% of the survivors, 63% of the fatalities, and 3% of the clinically unaffected pigs. The thoracic part of the cord was most commonly involved. Histologic cord lesions were found in 75 (63%) pigs: 83% of decompression illness survivors, 81% of the fatalities, and 23% of those clinically unaffected. Morphologically, hemorrhagic lesions were the most common (54%). Other common findings included spongiosis (48%), axonal swelling and loss (39%), and myelin degeneration (35%). White matter hemorrhages in the spinal cord were generally more numerous and extensive than those affecting the gray matter; however, gray matter hemorrhage was associated with increasing disease severity. Brain lesions were present in 23% of pigs and were most frequent in fatalities. Cerebellar and brain stem hemorrhages were the most common brain lesions; the molecular layer of the cerebellum appeared particularly susceptible. Pigs were chosen because of their cardiovascular and gas exchange similarities to humans. The clinical and histopathologic features of the pig model were compared with previous accounts in animals and humans; the model was judged analogous to severe human decompression illness. The finding of occult brain and cord lesions in clinically unaffected pigs is discussed. The model provides a useful tool for the study of dysbaric lesions of the central nervous system. Its noninvasive nature may facilitate the study of nervous system injury and repair processes.

The kangaroo rat as a model for type I decompression sickness.

This study involved 720 exposures of 70 kangaroo rats trapped in West Texas and showed that decompression-induced tail biting in this animal provides a good animal model for marginal limb bends in man. That this phenomenon can be reversed by recompression and pathological examination of the tail both indicated that a similar mechanism is probably involved in kangaroo rats and humans. Quantitatively, the most susceptible 20% of kangaroo rats can reproduce the no-stop decompression limits for man for exposure times ranging from 5 min to 8 h, for both air and helium-oxygen. Even the average minimum no-tail-biting depth of 46.2 fsw (2.40 ATA) for this species is much closer to the minimum bends depth of man than to the equivalent depth for other animals of its size, and is as good as the goats'. Its size and habits make the kangaroo rat much more convenient than other animals to use as a model for marginal decompression sickness, and particularly attractive economically for testing long helium-oxygen schedules and other means of decompression sickness prevention.

Decompression-induced bubble formation in salmonids: comparison to gas bubble disease.

The relationship of gas bubble disease (GBD) in fish to decompression-induced bubble formation was investigated with salmonids. Acute bioassays were used to determine equilibration times for critical effects in fish decompressed from depths to 200 fsw. It was found that equilibration of critical tissues was complete in 60-90 min. Salmonids and air-breathers are sensitive to decompressions at similar levels of supersaturation if elimination of excess gas following decompression is unrestricted. However, if elimination is restricted, bubble formation and growth increase accordingly. Tests with mixtures of He-O2, Ar-O2, N2-O2 (80% inert gas: 20% O2) and pure oxygen demonstrated that gas solubility as well as supersaturation (delta P), pressure ratio (initial pressure: final pressure), and absolute pressure must be considered in setting tolerance limits for any decompression. Gases with higher solubility are more likely to produce bubbles upon decompression. Oxygen, however, does not follow this relationship until higher pressures are reached, probably owing to its function in metabolism and in binding with hemoglobin. Tissue responses observed in both GBD and decompressed fish involved similar pathological effects at acute exposures. The circulatory system was consistently affected by bubbles that occluded vessels and blocked flow through the heart.