Venous gas embolism as a predictive tool for improving CNS decompression safety.

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached.

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals.

Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N(2)) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N(2) tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N(2) loading to management of the N(2) load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.

The relationship between venous gas bubbles and adverse effects of decompression after air dives.

The presence of gas bubbles in the vascular system is often considered a sign of decompression stress and several studies in the existing literature have addressed the relationship between the amount of bubbles detected by ultrasound Doppler systems and the incidence of decompression sickness. The use of ultrasound imaging has some important advantages to Doppler systems, and here we have looked at the relationship between the amount of intravascular gas bubbles detected by ultrasound echocardiography and the incidence of signs and symptoms of decompression stress after 203 air dives. The results show that venous gas bubbles detected by ultrasound imaging is a highly sensitive, although not specific, predictor of such adverse effects of decompression. Our results agree with the published concordance between Doppler detected bubbles and decompression sickness. We conclude that bubble detection by ultrasonic scanning of the heart can be used as a tool to assess the safety of decompression procedures for air dives.

The effect of endurance training on the rate of nitrogen elimination in women.

INTRODUCTION: The rate of nitrogen elimination may be an important factor in evaluating the risk of DCS following dives. The present study determined the reproducibility of a method for evaluating nitrogen elimination (series I), and the effect of chronic training on the nitrogen elimination in healthy young women (series II). METHODS: Nitrogen elimination was determined with subjects wearing an AGA full-face mask breathing pure oxygen. To evaluate the reproducibility of the method for nitrogen elimination, three tests were performed in six subjects in series I. Nitrogen elimination in series II was measured before and after the training period. The training protocol (series II) consisted of interval training, three times per week for eight weeks. Four repeated intervals alternated between four minutes at 90-95% of maximum heart rate and three minutes at 50-60%. RESULTS: There was no significant difference between the three repeated tests. Interval training for eight weeks increased maximum oxygen uptake by 22.1%. Endurance training did not influence the total nitrogen elimination at rest. CONCLUSION: The method for evaluating nitrogen elimination at rest was found to be reproducible. Improved aerobic capacity does not increase the rate of nitrogen elimination at rest.

Effect of a short-acting NO donor on bubble formation from a saturation dive in pigs.

It has previously been reported that a nitric oxide (NO) donor reduces bubble formation from an air dive and that blocking NO production increases bubble formation. The present study was initiated to see whether a short-acting NO donor (glycerol trinitrate, 5 mg/ml; Nycomed Pharma) given immediately before start of decompression would affect the amount of vascular bubbles during and after decompression from a saturation dive in pigs. A total of 14 pigs (Sus scrofa domestica of the strain Norsk landsvin) were randomly divided into an experimental (n = 7) and a control group (n = 7). The pigs were anesthetized with ketamine and alpha-chloralose and compressed in a hyperbaric chamber to 500 kPa (40 m of seawater) in 2 min, and they had 3-h bottom time while breathing nitrox (35 kPa O(2)). The pigs were all decompressed to the surface (100 kPa) at a rate of 200 kPa/h. During decompression, the inspired Po(2) of the breathing gas was kept at 100 kPa. Thirty minutes before decompression, the experimental group received a short-acting NO donor intravenously, while the control group were given equal amounts of saline. The average number of bubbles seen during the observation period decreased from 0.2 to 0.02 bubbles/cm(2) (P < 0.0001) in the experimental group compared with the controls. The present study gives further support to the role of NO in preventing vascular bubble formation after decompression.

Diving-induced venous gas emboli do not increase pulmonary artery pressure.

Venous gas emboli are frequently observed in divers even if proper decompression procedures are followed. This study was initiated to determine if pulmonary artery pressure increases in asymptomatic divers, which could increase the risk of arterial embolization due to passage of venous gas emboli from the right to the left side of the heart. Recordings of venous gas emboli and estimation of pulmonary artery pressure by non-invasive transthoracic echocardiography were applied in 10 recreational scuba diving volunteers before and 20, 40, 60, and 80 min after simulated dives to 18 m (80 min bottom time) in a hyperbaric chamber. The ratio between pulmonary artery acceleration time and right ventricular ejection time was used as an estimate of pulmonary artery pressure. None of investigated divers had signs of decompression sickness. Despite the post-dive presence of the venous gas emboli, measured in the region of the pulmonary valve annulus (mean=1.71 bubbles.cm-2, 40 min after dive), the ratio between pulmonary artery acceleration time and right ventricular ejection time did not decrease, but actually increased (from 0.43+/-0.06 to 0.49+/-0.06, 40 min after dive; p<0.05), suggesting a decrease in pulmonary artery pressure after the dive. We conclude that diving-induced venous gas bubbles do not cause significant changes in the central circulation which could increase the risk of arterial embolization.

Diving behaviour and decompression sickness among Galapagos underwater harvesters.

Diving conditions, dive profiles, vascular bubbles, and symptoms of decompression sickness (DCS) in a group of Galapagos commercial divers are described. They harvest sea cucumbers from small boats with surface supplied air (hookah). Dive profiles for 12 divers were recorded using dive loggers, and bubble formation was measured in the pulmonary artery. DCS symptoms were assessed by interview. A total of 380 immersions were recorded over a nine day period. The divers did on average 6.3 immersions per day, in a yo-yo pattern. Mean overall depth was 34.5 FSW. Maximum recorded depth was 107 FSW. Average bottom time per day per diver was 175 minutes. 82 % of all ascents exceeded the recommended maximum ascent rate of 30 FSW/ min. High bubble grades were observed on six occasions, but the test was unreliable. Muscle and joint pain was reported on five occasions, in three different divers. Symptoms were typically managed by analgesics, in-water recompression or not at all. The divers were extremely reluctant to seek professional help for DCS symptoms, mostly due to the high costs of treatment. We conclude that the fishermen dive beyond standard no-decompression limits, and that DCS symptoms are common.

A single air dive reduces arterial endothelial function in man.

During and after decompression from dives, gas bubbles are regularly observed in the right ventricular outflow tract. A number of studies have documented that these bubbles can lead to endothelial dysfunction in the pulmonary artery but no data exist on the effect of diving on arterial endothelial function. The present study investigated if diving or oxygen breathing would influence endothelial arterial function in man. A total of 21 divers participated in this study. Nine healthy experienced male divers with a mean age of 31 +/- 5 years were compressed in a hyperbaric chamber to 280 kPa at a rate of 100 kPa min(-1) breathing air and remaining at pressure for 80 min. The ascent rate during decompression was 9 kPa min(-1) with a 7 min stop at 130 kPa (US Navy procedure). Another group of five experienced male divers (31 +/- 6 years) breathed 60% oxygen (corresponding to the oxygen tension of air at 280 kPa) for 80 min. Before and after exposure, endothelial function was assessed in both groups as flow-mediated dilatation (FMD) by ultrasound in the brachial artery. The results were compared to data obtained from a group of seven healthy individuals of the same age who had never dived. The dive produced few vascular bubbles, but a significant arterial diameter increase from 4.5 +/- 0.7 to 4.8 +/- 0.8 mm (mean +/- s.d.) and a significant reduction of FMD from 9.2 +/- 6.9 to 5.0 +/- 6.7% were observed as an indication of reduced endothelial function. In the group breathing oxygen, arterial diameter increased significantly from 4.4 +/- 0.3 mm to 4.7 +/- 0.3 mm, while FMD showed an insignificant decrease. Oxygen breathing did not decrease nitroglycerine-induced dilatation significantly. In the normal controls the arterial diameter and FMD were 4.1 +/- 0.4 mm and 7.7 +/- 0.2.8%, respectively. This study shows that diving can lead to acute arterial endothelial dysfunction in man and that oxygen breathing will increase arterial diameter after return to breathing air. Further studies are needed to determine if these mechanisms are involved in tissue injury following diving.

A randomized, double blind study of the prophylactic effect of hyperbaric oxygen therapy on migraine.

In a double blind, placebo-controlled study to assess the prophylactic effect of hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a treatment group receiving three sessions of hyperbaric oxygen, or a control group receiving three hyperbaric air treatments. The patients were instructed to keep a standardized migraine diary for eight weeks before and after the treatment. Thirty-four patients completed the study. Our primary measure of efficacy was the difference between pre- and post-treatment hours of headache per week. The results show a nonsignificant reduction in hours of headache for the hyperbaric oxygen group compared to the control group. Levels of endothelin-1 in venous blood before and after treatment did not reveal any difference between the hyperbaric oxygen and control groups. We conclude that the tested protocol does not show a significant prophylactic effect on migraine and does not influence the level of endothelin-1 in venous blood.

Decompression profile and bubble formation after dives with surface decompression: experimental support for a dual phase model of decompression.

The present study was initiated in order to determine the effect of decompression profiles on bubble formation following surface decompression using oxygen. Following an air dive to 496 kPa (130 fsw) for 90 minutes, three different profiles were tested in the pig; a USN staged decompression profile, a profile using linear continuous decompression with the same total decompression time as the USN profile (ABI) and a linear profile with half the total decompression time compared to the the first two (ABII). The subsequent surface decompression at 220 kPa lasted 68 minutes for all three schedules. The study demonstrated that, following final decompression, the two linear profiles produced the lowest amount of vascular gas, with the fastest profile producing significantly less bubbles in the Pulmonary artery than the other two. Similar results were obtained in the jugular vein. The results are in qualitative agreement with model simulation using the Reduced Gradient Bubble Model (RGBM), demonstrating that the controlling tissues are reduced from those with a half time of 40 minutes using the USN procedure to 5 minutes using the fastest linear profile.

Evaluation of cerebral gas retention and oedema formation in decompressed rats by using a simple gravimetric method.

OBJECTIVE: The objective of the study is twofold: first, to develop a specific gravity method for distinguishing between bubbles and oedema following decompression, and, second, to evaluate the extent to which the change in specific gravity is due to retained gas in cerebral tissue. METHODS: A brombenzene/kerosene gradient column was used to measure changes in brain specific gravity at 100 and 300 kPa, respectively. This study was performed on 23 rats. Non-exposed rats constituted the control group A (n=6). The exposed animals were divided into two groups according to the number of bubbles they developed upon decompression; group B (bubble grade 0-2, n=9) and group C (bubble grade 3-5, n=8). RESULTS: Cerebral gas retention was determined by increasing the pressure on the gradient column from 100 to 300kPa. Median specific gravity of the brain at 300kPa bar was significantly higher compared to 100 kPa for the decompressed groups B (p= 0.018) and C (p=0.012), thus implying gas retention. The cerebral gas volume was significantly higher for rats with a high bubble score compared to rats with a low bubble score (p=0.043). However, the major contribution to the change in specific gravity was due to oedema formation. CONCLUSION: The brombenzene/kerosene gradient column was found to be a sensitive method for distinguishing between gas retention and oedema formation in decompressed animals. There was a higher gas retention in rats with a high bubble score compared to rats with a low bubble score. The major contribution to the change in specific gravity in decompressed animals is due to oedema formation.

The effect of air bubbles on rabbit blood brain barrier.

Several investigators have claimed that the blood brain barrier (BBB) may be broken by circulating bubbles, resulting in brain tissue edema. The aim of this study was to examine the effect of air bubbles on the permeability of BBB. Three groups of 6 rabbits were infused an isoosmotic solution of NaCl w/macrodex and 1% Tween. The solution was saturated with air bubbles and infused at rates of 50-100 ml hr(-1), a total of 1.6, 3.3, or 6.6 ml in each group, respectively. Two groups, each consisting of 6 rabbits, served as controls; one was infused by a degassed isoosmotic NaCl solution and one was sham-operated. All animals were left for 30 min before they were sacrificed. Specific gravity of brain tissue samples was determined using a brombenzene/kerosene gradient column, where a decrease in specific gravity indicates local brain edema. Specific gravity was significantly lower for left (P = 0.037) and right (P = 0.012) hemisphere white matter and left (P = 0.0015) and right (P = 0.002) hemisphere gray matter for the bubble-infused animals compared to the sham-operated ones. Infusion of degassed NaCl solution alone affected white left (P= 0.011) and right (P= 0.013), but not gray matter of both hemispheres. We speculate that insufficient degassing of the fluid may cause the effect of NaCl solution on the BBB of the white matter, indicating that the vessels of the white matter are more sensitive to gas bubbles than gray matter. Increasing the number of infused bubbles had no further impact on the development of cerebral edema, indicating that a threshold value was reached already at the lowest concentration of bubbles.

Microdialysis in cisterna magna during cerebral air embolism in swine.

Arterial gas embolism may occur as a consequence of lung rupture, decompression sickness, following operative procedures or as accidental infusion of gas during various diagnostic procedures. It can lead to severe morbidity or even death. Microdialysis is a technique that has been extensively used for evaluating localized changes in the brain. The microdialysis probe is only capable of measuring changes in the immediate adjacent tissue. In arterial gas embolism the changes are multifocal. Thus a probe located in the cerebral cortex will not detect the total amount of damage. We used microdialysis in the cisterna magna of 9 anaesthetized pigs to study the diffuse injury following arterial gas embolism. After injection of 5.0 mL of air in the internal carotid artery, we found a significantly increased lactate-pyruvate ratio in the cerebrospinal fluid, lasting for 2 hours. This indicates anaerobic metabolism. Mean levels of glycerol were significantly increased, indicating membrane disruption. Glutamate levels were also elevated, although not significantly. The injection of air affected carotid flow. Flow in the carotid artery of the side of injection decreased significantly, but returned to baseline in 1 hour. Flow in the contralateral carotid was increased, but not significantly. We conclude that massive air embolism causes ischemia and reduced blood flow in the brain that can be detected in the cisterna magna.

Aerobic endurance training reduces bubble formation and increases survival in rats exposed to hyperbaric pressure.

1. The formation of bubbles is the basis for injury to divers after decompression, a condition known as decompression illness. In the present study we investigated the effect of endurance training in the rat on decompression-induced bubble formation. 2. A total of 52 adult female Sprague-Dawley rats (300-370 g) were randomly assigned to one of two experimental groups: training or sedentary control. Trained rats exercised on a treadmill for 1.5 h per day for 1 day, or for 2 or 6 weeks (5 days per week) at exercise intervals that alternated between 8 min at 85-90% of maximal oxygen uptake (VO2,max) and 2 min at 50-60% of VO2,max. Rats were compressed (simulated dive) in a decompression chamber in pairs, one sedentary and one trained, at a rate of 200 kPa x min(-1) to a pressure of 700 kPa, and maintained for 45 min breathing air. At the end of the exposure period, rats were decompressed linearly to the 'surface' (100 kPa) at a rate of 50 kPa x min(-1). Immediately after reaching the 'surface' (100 kPa) the animals were anaesthetized and the right ventricle was insonated using Doppler ultrasound. 3. Intensity-controlled interval training significantly increased VO2,max by 12 and 60% after 2 and 6 weeks, respectively. At 6 weeks, left and right ventricular weights were 14 and 17 % higher, respectively, in trained compared to control rats. No effect of training was observed on skeletal muscle weight. Bubble formation was significantly reduced in trained rats after both 2 and 6 weeks. However, the same effect was seen after a single bout of aerobic exercise lasting 1.5 h on the day prior to decompression. All of the rats that exercised for 1.5 h and 2 weeks, and most of those that trained for 6 weeks, survived the protocol, whereas most sedentary rats died within 60 min post-decompression. 4. This study shows that aerobic exercise protects rats from severe decompression and death. This may be a result of less bubbling in the trained animals. The data showed that the increase in aerobic capacity per se was not the main mechanism, but rather an acute effect that was most notable 20 h after a single, or the last, exercise bout, with less effect after 48 h.

[Iatrogenic gas embolism]. / Iatrogen gassemboli.

BACKGROUND: Gas embolism may occur as a consequence of lung injury, decompression sickness, surgery or as accidental infusion of gas during various diagnostic procedures. Iatrogenic gas embolism is often not recognised, but can lead to severe morbidity or even death. MATERIAL AND METHODS: We present a case of iatrogenic paradoxical air embolism caused by a defect in a central venous catheter. A review of the literature is given. RESULTS: The patient recovered gradually, but suffered significant neurological deficits. INTERPRETATION: Gas embolism must be considered as a differential diagnosis when a patient presents with unexplained neurological symptoms. Prompt treatment using oxygen at increased pressures (hyperbaric oxygen treatment) may be lifesaving and prevent serious sequelae.

Arterial air embolism after venous air infusion in newborn piglets.

UNLABELLED: In the newborn period, decreased right atrial pressure results in functional closure of the foramen ovale (FO). The objective of this study was to investigate whether air bubbles infused in the vena cava will pass through the FO into the arterial circulation in a newborn animal. Since air tends to rise to the highest point in a fluid, the study also investigated whether the animal's position could influence arterialization of air. Twelve 1-3-d-old piglets were anaesthetized and mechanically ventilated, and had catheters placed in the vena cava for infusion of air, in the aorta for blood gas and blood pressure measurements, and in the pulmonary artery for pressure measurements. After stabilization, 0.05 ml kg(-1) per minute of air was infused for 25 min followed by a 3 h observation period. Six piglets were placed in the left, and six in the right lateral recumbent position. Air bubbles in the left atrium or ventricle was monitored by echocardiography. Ultrasound Doppler probes were placed on both carotid arteries for detection of air embolism. Gas bubbles were detected in the left ventricle within 45 s of air infusion in 11 of 12 piglets. Eight piglets had air bubbles in the carotid arteries. Mean pulmonary arterial pressure (PAP) increased significantly after 1 min of air infusion, whereas mean systemic arterial pressure remained unchanged. When arterial air embolism occurred, PAP had not increased significantly. The time to reach maximum PAP with the animals in the left recumbent position was significantly shorter than in the right. CONCLUSION: This study shows that venous gas bubbles enter the arterial circulation through the FO in newborn piglets and that body position may influence the haemodynamic effect of these bubbles.

Comparison of three different ultrasonic methods for quantification of intravascular gas bubbles.

For evaluating different decompression schedules, the use of ultrasound is common. Systems based on the Doppler principle have mostly been used. However, ultrasonic scanners producing images where the bubbles are easily detected, may be an alternative, because analysis of the signals is simpler than when using Doppler methods. In this study, three methods of bubble detection were used following a series of air dives. The divers were investigated using a "blind" Doppler system where only auditory signals were used for positioning the probe. They were also studied using ultrasonic images and finally an "image-assisted" Doppler method was used, where the sample volume of the Doppler system was positioned using the images. Both Doppler systems were pulsed Doppler systems. The agreement between the methods was determined using weighted kappa statistics. The results show that, at rest, the agreement between the images and the blind Doppler method was very good, and between the two Doppler methods and the images and the image-assisted method the agreement was good. Generally, the agreement is better at higher bubble grades. After movement, the agreement was not good. We conclude that grades from the different methods can be directly compared at rest.

Man in extreme environments.

Humans have demonstrated the ability to live and work in many adverse environments. Many examples demonstrate that our understanding of humans ability to adapt to extreme environments is limited, but it is reasonable to assume that the main problems in space exploration will be psychological and social. It is argued that polar expeditions of an earlier age are a better model for space exploration than confinement studies or Antarctic overwintering. Some aspects of the reason for the success of these expeditions are discussed and the lessons that can be used are pointed out.

Lack of effect of anti-C5a monoclonal antibody on endothelial injury by gas bubbles in the rabbit after decompression.

Previous studies have shown that gas bubbles activate the complement system in vitro, generating C5a. The effect of anti-C5a monoclonal antibody 4B1C11 in preventing endothelial damage caused by decompression in the pulmonary artery of the rabbit was examined. The endothelial response was measured using tension measurements in the blood vessel wall. The mean bubble count for all rabbits (n = 24) was 4.2+/-3.1 bubbles x cm(-2), and ranged from 0 to 15 bubbles x cm(-2). Animals with many bubbles showed significantly more vascular damage than those with fewer bubbles. Anti-C5a monoclonal antibody could not prevent endothelial damage than that occurred after exposure to this level of gas bubbles. The maximum number of gas bubbles present is important for the endothelial damage. We speculate that the endothelial damage observed was mainly mechanical. A possible beneficial effect of anti-C5a antibody can thus be masked at a high degree of bubble generation. This study, together with a previous paper, demonstrates that gas bubbles cause endothelial damage from decompression both in the pig and in the rabbit.