The largest of August Krogh animals: Physiology and biomechanics of the blue whale revisited.

The blue whale is the largest animal ever. This gigantism probably evolved to exploit seasonal krill blooms, where massive feasts allow for accumulation of large blubber reserves that can fuel their low mass specific metabolism during prolonged periods of fasting. Until recently, the physiology and biomechanics of blue whales could only be inferred from anatomical inspections, but the recent development of biologging tags now provide unique insights into how these ocean giants function and interact with their environment. Their mandibles, the largest bones ever to evolve, along with a highly expandable buccal cavity, enable an extreme and dynamic bulk feeding behavior. During a lunge feeding event, blue whales accelerate up to 5 m/s to engulf a volume prey laden water that is commensurate with the whale's gigantic body size. Perhaps due to the costs of such extreme foraging, their dive times of 10-15 min are much shorter than scaling would predict for their size. Like other diving animals, blue whales display a dive response with heart rates down to 4 BPM to prolong dive times and perhaps mitigate decompression sickness. Blue whales make the lowest and most energetic calls of any mammal with ocean traversing potential under natural ambient noise conditions. However, communication space may be severely reduced due to pervasive shipping noise. We hope that an increasing ability to study the physiology and behavior of blue whales and other marine megafauna will enable informed decisions and ensure our permanent co-existence in the face of increasing human encroachment into marine habitats.

On-board study of gas embolism in marine turtles caught in bottom trawl fisheries in the Atlantic Ocean.

Decompression sickness (DCS) was first diagnosed in marine turtles in 2014. After capture in net fisheries, animals typically start showing clinical evidence of DCS hours after being hauled on-board, often dying if untreated. These turtles are normally immediately released without any understanding of subsequent clinical problems or outcome. The objectives of this study were to describe early occurrence and severity of gaseous embolism (GE) and DCS in marine turtles after incidental capture in trawl gear, and to provide estimates of on-board and post-release mortality. Twenty-eight marine turtles were examined on-board fishing vessels. All 20 turtles assessed by ultrasound and/or post-mortem examination developed GE, independent of season, depth and duration of trawl and ascent speed. Gas emboli were obvious by ultrasound within 15 minutes after surfacing and worsened over the course of 2 hours. Blood data were consistent with extreme lactic acidosis, reduced glomerular filtration, and stress. Twelve of 28 (43%) animals died on-board, and 3 of 15 (20%) active turtles released with satellite tags died within 6 days. This is the first empirically-based estimate of on-board and post-release mortality of bycaught marine turtles that has until now been unaccounted for in trawl fisheries not equipped with turtle excluder devices.

In vitro evidence of decompression bubble dynamics and gas exchange on the luminal aspect of blood vessels: Implications for size distribution of venous bubbles.

We found that lung surfactant leaks into the bloodstream, settling on the luminal aspect of blood vessels to create active hydrophobic spots (AHS). Nanobubbles formed by dissolved gas at these AHS are most probably the precursors of gas micronuclei and decompression bubbles. Sheep blood vessels stretched on microscope slides, and exposed under saline to hyperbaric pressure, were photographed following decompression. Photographs of an AHS from a pulmonary vein, containing large numbers of bubbles, were selected in 1-min sequences over a period of 7 min, starting 18 min after decompression from 1,013 kPa. This showed bubble detachment, coalescence and expansion, as well as competition for dissolved gas between bubbles. There was greater expansion of peripheral than of central bubbles. We suggest that the dynamics of decompression bubbles on the surface of the blood vessel may be the closest approximation to true decompression physiology, and as such can be used to assess and calibrate models of decompression bubbles. We further discuss the implications for bubble size in the venous circulation.

Influence of oxygen enriched gases during decompression on bubble formation and endothelial function in self-contained underwater breathing apparatus diving: a randomized controlled study.

AIM: To assess the effect of air, gas mixture composed of 50% nitrogen and 50% oxygen (nitrox 50), or gas mixture composed of 1% nitrogen and 99% oxygen (nitrox 99) on bubble formation and vascular/endothelial function during decompression after self-contained underwater breathing apparatus diving. METHODS: This randomized controlled study, conducted in 2014, involved ten divers. Each diver performed three dives in a randomized protocol using three gases: air, nitrox 50, or nitrox 99 during ascent. The dives were performed on three different days limited to 45 m sea water (msw) depth with 20 min bottom time. Nitrogen bubbles formation was assessed by ultrasound detection after dive. Arterial/endothelial function was evaluated by brachial artery flow mediated dilatation (FMD) before and after dive. RESULTS: Nitrox 99 significantly reduced bubble formation after cough compared with air and nitrox 50 (grade 1 vs 3 and vs 3, respectively, P=0.026). Nitrox 50 significantly decreased post-dive FMD compared with pre-dive FMD (3.62 ± 5.57% vs 12.11 ± 6.82% P=0.010), while nitrox 99 did not cause any significant change. CONCLUSION: Nitrox 99 reduced bubble formation, did not change post-dive FMD, and decreased total dive duration, indicating that it might better preserve endothelial function compared with air and nitrox 50 dive protocols.

Diving physiopathology: the end of certainties? Food for thought.

Our understanding of decompression physiopathology has slowly improved during this last decade and some uncertainties have disappeared. A better understanding of anatomy and functional aspects of patent foramen ovale (PFO) have slowly resulted in a more liberal approach toward the medical fitness to dive for those bearing a PFO. Circulating vascular gas emboli (VGE) are considered the key actors in development of decompression sickness and can be considered as markers of decompression stress indicating induction of pathophysiological processes not necessarily leading to occurrence of disease symptoms. During the last decade, it has appeared possible to influence post-dive VGE by a so-called "preconditioning" as a pre-dive denitrogenation, exercise or some pharmacological agents. In the text we have deeply examined all the scientific evidence about this complicated but challenging theme. Finally, the role of the "normobaric oxygen paradox" has been clarified and it is not surprising that it could be involved in neuroprotection and cardioprotection. However, the best level of inspired oxygen and the exact time frame to achieve optimal effect is still not known. The aim of this paper was to reflect upon the most actual uncertainties and distil out of them a coherent, balanced advice towards the researchers involved in gas-bubbles-related pathologies.

Diving Headache.

This review will focus on the most recent information regarding the ICHD-3 definition of diving headache as well as other important causes of diving headache that are not listed in the ICHD-3 classification system. The paper will discuss etiology, diagnosis, and management of these disorders, focusing, when possible, on the newest research available. ICHD-3 diving headache is due to hypercapnia and is treated accordingly with oxygen. Other causes of diving headache range from decompression sickness to external compression headache to primary headache disorders, such as migraine. Correctly determining the underlying cause of the diving headache is critical to management and relies on history taking and physical exam. The pathophysiology of newly described types of diving headache, such as diving ascent headache, remains under investigation but may be related to other homeostatic headache causes, such as airplane headache. Further investigation may yield more information regarding management as well as possible insight into other headache disorders.

Elevated Environmental Carbon Dioxide Exposure Confounding Physiologic Events in Aviators?

INTRODUCTION: Physiological events (PEs) are a growing problem for US military aviation with detrimental risks to safety and mission readiness. Seeking causative factors is, therefore, of high importance. There is no evidence to date associating carbon dioxide (CO2) pre-flight exposure and decompression sickness (DCS) in aviators. MATERIALS AND METHODS: This study is a case series of six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. The analysis includes retrospective review of flight and environmental data to further assess a possible link between CO2 levels and altitude physiologic events (PEs). IRB approval was obtained for this study. RESULTS: This case series presents six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. Another three aviators were also exposed to a RDE, but remained asymptomatic. All events involved tactical jet aircraft flying at an average of 35,600' Mean Sea Level (MSL) when a RDE occurred, Retrospective reviews led to the discovery that the affected individuals were exposed, pre-flight, to poor indoor air quality demonstrated by elevated levels of measured CO2. CONCLUSION: PEs are a growing safety concern for the aviation community in the military. As such, increasing measures are taken to ensure safety of flight and completion of the mission. To date, there is no correlation of CO2 exposure and altitude DCS. While elevated CO2 levels cannot be conclusively implicated as causative, this case series suggests a potential role of CO2 in altitude DCS through CO2 direct involvement with emboli gas composition, as well as pro-inflammatory cascade. Aviators exposed to elevated CO2 in poorly ventilated rooms developed PE symptoms consistent with DCS, while at the same command, aviators that were exposed to a well ventilated room did not. This report is far from an answer, but does demonstrate an interesting case series that draws some questions about CO2's role in these aviator's DCS experience. Other explanations are plausible, including the accurate diagnosis of DCS, health variables amongst the aviators, and differences in aircraft and On-Board Oxygen Generation Systems (OBOGS). For a better understanding, the role of environmental CO2 and pre-flight exposure as a risk of DCS should be reviewed.

Bubble Formation in Children and Adolescents after Two Standardised Shallow Dives.

Circulating venous bubbles after dives are associated with symptoms of decompression sickness in adults. Up to now it is not known to what extent children and adolescents are subjected to a bubble formation during their shallow dives and if there are possible indications for that. The aim of this pilot study is to investigate whether bubbles and/or symptoms occur after standardised repeated dives performed by young divers. 28 children and adolescents (13.5±1.1 years) carried out two 25 min dives to a depth of 10 m with a 90 min surface interval. Before and after, echocardiographic data were recorded and evaluated with regard to circulating bubbles with an extended Eftedal-Brubakk-Scale by 2 different examiners. Bubbles were observed for a total of 6 subjects, Grade I (n=5) and Grade III (n=1). None of them showed any symptoms of decompression sickness. No differences were established regarding potential influencing factors on bubble formation between the groups with and without bubbles. The results indicate that even relatively shallow and short dives can generate venous bubbles in children and adolescents. To what extent this relates to the decompression sickness or clinical symptoms cannot be validated at this point.

Taravana, vestibular decompression illness, and autochthonous distal arterial bubbles.

Decompression bubbles can develop only from pre-existing gas micronuclei. These are the nanobubbles which appear on active hydrophobic spots (AHS) found on the luminal aspect of all blood vessels. Following decompression, with the propagation of blood along the arterial tree, diffusion parameters cause increased transfer of nitrogen from the tissue into the artery, and more so if perfusion is low. Taravana is a neurological form of decompression illness (DCI) prevalent in repeated breath-hold diving. A nanobubble on an AHS in a distal artery of the brain may receive an influx of nitrogen after each dive until it occludes the arterial blood flow. The vestibular organ has very low perfusion compared with the brain and the cochlea of the inner ear. We suggest that a nanobbubble on an AHS in the distal artery of the vestibular organ will receive a high influx of nitrogen from the surrounding tissue after decompression due to the low nitrogen clearance, thus expanding to cause vestibular DCI.

Acute decompression following simulated dive conditions alters mitochondrial respiration and motility.

While barotrauma, decompression sickness, and drowning-related injuries are common morbidities associated with diving and decompression from depth, it remains unclear what impact rapid decompression has on mitochondrial function. In vitro diving simulation was performed with human dermal fibroblast cells subjected to control, air, nitrogen, and oxygen dive conditions. With the exception of the gas mixture, all other related variables, including absolute pressure exposure, dive and decompression rates, and temperature, were held constant. High-resolution respirometry was used to examine key respiratory states. Mitochondrial dynamic function, including net movement, number, and rates of fusion/fission events, was obtained from fluorescence microscopy imaging. Effects of the dive conditions on cell cytoskeleton were assessed by imaging both actin and microtubules. Maximum respiration was lower in fibroblasts in the air group than in the control and nitrogen groups. The oxygen group had overall lower respiration when compared with all other groups. All groups demonstrated lower mitochondrial motility when compared with the control group. Rates of fusion and fission events were the same between all groups. There were visible differences in cell morphology consistent with the actin staining; however, there were no appreciable changes to the microtubules. This is the first study to directly assess mitochondrial respiration and dynamics in a cell model of decompression. Both hyperbaric oxygen and air dive conditions produce deleterious effects on overall mitochondrial health in fibroblasts.

The Gradient Perfusion Model Part 1: Why and at what sites decompression sickness can occur.

INTRODUCTION: Decompression sickness (DCS) is manifested by the quantity and location of bubbles in body tissues after reduction in ambient pressures. Models have been formulated to explain why bubbles form, but none provide satisfactory explanations as to why the findings of DCS occur as they do. This first of a three-part series explains why and at what sites DCS occurs. MATERIALS AND METHODS: Over a 50-year span and 500 cases of DCS we have managed, it has become apparent that almost all "unexplained" DCS (i.e., cases with no obvious explanation as to how/why they occurred) have physiological explanations. The vagaries of the physiology of tissue perfusion and the physics of gradients as a cause of autochthonous bubble formation were analyzed. FINDINGS: Perfusion is highly variable, with so-called "fast" tissues (i.e., tissues with a rapid rate of saturation) requiring a constant blood supply, "intermediate" tissues requiring a blood supply proportional to needs, and "slow" tissues having minimal perfusion requirements. The 5-liter blood volume in a vascular system with greater than a 20-liter capacity requires careful regulation. Disruptions in the regulation and/or overwhelming gradients explain why DCS occurs. CONCLUSIONS: Our Gradient-Perfusion Model provides an explanation as to why disordering events account for almost all cases of unexplained DCS. We propose that this latter term be discarded and "disordering events" be sought for DCS cases that have no obvious explanations.

The Gradient Perfusion Model Part 2: Substantiation of the GPM with clinical cases.

Introduction: In Part 1 of this three-part series, we provided an explanation as to why and at what sites decompression sickness (DCS) occurs, using the Gradient-Perfusion Model (GPM). In this part, we provide information to substantiate the concept and present clinical cases that were initially labeled as "unexplained DCS," but later disordering events were identified to explain the clinical presentations. Materials and Methods: Among 500 cases of DCS we have managed for over 50 years, a cohort of these patients was initially diagnosed as unexplained DCS. However, some have shown that disordering events are the likely cause of their DCS. Results: By pairing the tissue involved with the patient's dive history, a gradient-perfusion imbalance connection was identified. In all serious (Type 2) presentations of DCS, alterations in perfusion of the fast tissues were able to account for the clinical findings. The consequences demonstrated that the gradients overwhelmed the ability of altered perfusion to offgas/offload the inert gas. Pain-only and peripheral neuropathy presentations involved both intermediate and slowly perfused tissues. Rather than perfusion, gradient limitations were the reasons for the clinical presentations of these patients. Conclusions: The GPM accounts for signs and symptom presentations in DCS. This provides the basis for appropriate treatments and logical recommendations for return to diving. We recommend that the label "unexplained DCS" be discontinued and that the GPM be used to determine the cause. Once the cause is established, "DCS due to disordered decompression" becomes the appropriate term.

Variability in circulating gas emboli after a same scuba diving exposure.

PURPOSE: A reduction in ambient pressure or decompression from scuba diving can result in ultrasound-detectable venous gas emboli (VGE). These environmental exposures carry a risk of decompression sickness (DCS) which is mitigated by adherence to decompression schedules; however, bubbles are routinely observed for dives well within these limits and significant inter-personal variability in DCS risk exists. Here, we assess the variability and evolution of VGE for 2 h post-dive using echocardiography, following a standardized pool dive in calm warm conditions. METHODS: 14 divers performed either one or two (with a 24 h interval) standardized scuba dives to 33 mfw (400 kPa) for 20 min of immersion time at NEMO 33 in Brussels, Belgium. Measurements were performed at 21, 56, 91 and 126 min post-dive: bubbles were counted for all 68 echocardiography recordings and the average over ten consecutive cardiac cycles taken as the bubble score. RESULTS: Significant inter-personal variability was demonstrated despite all divers following the same protocol in controlled pool conditions: in the detection or not of VGE, in the peak VGE score, as well as time to VGE peak. In addition, intra-personal differences in 2/3 of the consecutive day dives were seen (lower VGE counts or faster clearance). CONCLUSIONS: Since VGE evolution post-dive varies between people, more work is clearly needed to isolate contributing factors. In this respect, going toward a more continuous evaluation, or developing new means to detect decompression stress markers, may offer the ability to better assess dynamic correlations to other physiological parameters.

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.

A unique case of a 70-hour decompression sickness latency.

We report a unique and well-documented case of a type II decompression sickness (DCS) with a latency interval of 70 hours. It may raise divers' awareness and help medical practitioners to keep suspect divers under close observation longer than before and identify and treat DCS accordingly.

Iso-risk air no decompression limits after scoring marginal decompression sickness cases as non-events.

Decompression sickness (DCS) in humans is associated with reductions in ambient pressure that occur during diving, aviation, or certain manned spaceflight operations. Its signs and symptoms can include, but are not limited to, joint pain, radiating abdominal pain, paresthesia, dyspnea, general malaise, cognitive dysfunction, cardiopulmonary dysfunction, and death. Probabilistic models of DCS allow the probability of DCS incidence and time of occurrence during or after a given hyperbaric or hypobaric exposure to be predicted based on how the gas contents or gas bubble volumes vary in hypothetical tissue compartments during the exposure. These models are calibrated using data containing the pressure and respired gas histories of actual exposures, some of which resulted in DCS, some of which did not, and others in which the diagnosis of DCS was not clear. The latter are referred to as marginal DCS cases. In earlier works, a marginal DCS event was typically weighted as 0.1, with a full DCS event being weighted as 1.0, and a non-event being weighted as 0.0. Recent work has shown that marginal DCS events should be weighted as 0.0 when calibrating gas content models. We confirm this indication in the present work by showing that such models have improved performance when calibrated to data with marginal DCS events coded as non-events. Further, we investigate the ramifications of derating marginal events on model-prescribed air diving no-stop limits.

Probabilistic pharmacokinetic models of decompression sickness in humans: Part 2, coupled perfusion-diffusion models.

Decompression sickness (DCS) can be experienced following a reduction in ambient pressure; such as that associated with diving or ascent to high altitudes. DCS is believed to result when supersaturated inert gas dissolved in biological tissues exits solution and forms bubbles. Models to predict the probability of DCS are typically based on nitrogen and/or helium gas uptake and washout in several theoretical tissues, each represented by a single perfusion-limited compartment. It has been previously shown that coupled perfusion-diffusion compartments are better descriptors than solely perfusion-based models of nitrogen and helium uptake and elimination kinetics observed in the brain and skeletal muscle of sheep. In this work, we examine the application of these coupled pharmacokinetic structures with at least one diffusion compartment to the prediction of the incidence of decompression sickness in humans. We compare these models to LEM-NMRI98, a well-described U.S. Navy gas content model, consisting of three uncoupled perfusion-limited compartments incorporating oxygen and linear-exponential kinetics. Pharmacokinetic gas content models with a diffusion component describe the probability of DCS in human bounce dives made with air, single non-air bounce dives, and oxygen decompression dives better than LEM-NMRI98. However, for the full data set, LEM-NMRI98 remains the best descriptor of the data.

Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

Medical Management and Risk Reduction of the Cardiovascular Effects of Underwater Diving.

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.