Role of surface-active phospholipids in gastric cytoprotection.

Intragastric administration of a liposomal surfactant suspension markedly reduced acid-induced gastric ulcerogenesis and bleeding in rats. The concentration of surface-active molecules intrinsically present in the gastric mucosa was increased two to six times by administration of 16,16-dimethyl prostaglandin E2. Thus, local accumulation of surface-active phospholipids may be an integral component of the cytoprotective mechanism activated by prostaglandin treatment.

Hyperbaric oxygen pre-breathe modifies the outcome of decompression sickness.

Deep sea divers, aviators and astronauts are at risk of decompression sickness when the ambient pressure reductions exceed a critical threshold. Venous bubbles associated with decompression sickness have the potential to react with the vascular membrane and adjacent blood products, eliciting an inflammatory cascade. Preventive measures usually involve careful decompression procedures to avoid or reduce bubble formation. De-nitrogenation with 100% oxygen pre-breathing as a preventive measure has been well established at least in altitude decompression exposures. The objective of this study was to determine the physiological and biochemical effects of Hyperbaric Oxygen Pre-breathe (HBOP) upon decompression from a hyperbaric exposure. Male Sprague-Dawley rats were randomly assigned to one of eight groups. Two experimental groups received HBOP at 1 and 18 hours prior to decompression, as compared with ground level oxygen or non-treated groups that still experienced decompression stress, and the associated non-decompressed controls. The results showed decreased extravascular lung water (pulmonary edema), bronchoalveolar lavage and pleural protein and arterial, broncho-alveolar lavage, and urine leukotriene E4 (LKE4) levels in both the 1Hr and 18Hr HBOP decompressed rats compared to non-oxygenated decompressed rats, as well as a decreased overall expression of signs of decompression sickness. This study indicates that HBOP-treated rats exhibit fewer signs and complications of decompression sickness compared with non-treated or ground level oxygen treated rats.

Transesophageal echocardiographic study of venous air embolism following pneumomediastinum in dogs.

BACKGROUND: Continuous venous air emboli have been detected in the inferior vena cava and smaller veins using transesophageal echocardiography in patients with positive pressure ventilation and associated pulmonary barotrauma. The authors hypothesized that gas entered the venous circulation, following dissection of small vessels at several sites in the subcutaneous or retro-peritoneal soft tissues. OBJECTIVE: The present study was designed to determine if a comparable venous gas embolism occurred in anesthetized dogs, after creation of a pneumomediastinum. DESIGN: Using transesophageal echocardiography, we observed 11 anesthetized dogs mechanically ventilated with positive end-expiratory pressure, while mediastinal air was introduced through a catheter at a rate of 0.5 ml/kg/min. RESULTS: A continuous stream of bubbles appeared in the inferior vena cava in 8/11 dogs (73%) after an infusion period of 280 +/- 81 min. A surge of bubbles was commonly observed following abdominal massage and was often associated with a transient decrease of end-tidal carbon dioxide tensions. In two dogs the air infusion rate was reduced to 0.25 mg/kg/min, and bubbles were detected in the inferior vena cava for as long as 16 consecutive hours. CONCLUSION: We conclude that in anesthetized dogs mechanically ventilated with positive end-expiratory pressure, unremitting pneumomediastinum is usually followed by continuous venous air embolism. A mechanism hypothesized for venous gas entry in the clinical condition of positive end-expiratory pressure ventilation with subcutaneous gas is suggested by this model.

Transpulmonary passage of venous air emboli.

Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml X kg-1 X min-1 in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml X kg-1 X min-1. When the air doses were increased to 0.35 ml X kg-1 X min-1, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50% of the animals and reaching 71% for 0.40 ml X kg-1 X min-1. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml X kg-1 X min-1.

Surfactants identified in lung lymph and their ability to act as abhesives.

Phospholipid has been extracted from pulmonary lymph collected from 10 dogs. Thin-layer chromatography was used to identify phosphatidylcholine (PC) 55.6 +/- 2.9%, sphingomyelin 21.3 +/- 1.7%, phosphatidylethanolamine 11.2 +/- 4.9%, and lysophosphatidylcholine 5.9 +/- 0.8%. All extracts proved highly surface active, reducing the surface tension of saline to 27.7 +/- 0.7 dyn/cm upon 80% film compression and increasing the maximum contact angle on glass (theta) from 7 +/- 1 to 47.4 +/- 1.4 degrees. The hydrophobic properties induced on glass were further demonstrated by the ability to cause saline to withdraw and expose a dry surface. A standard adhesion test was used to measure the "tack" produced by the major proteins in lymph. However, when the surface energy of the hydrophilic glass surfaces was reduced by a monolayer of lymph phospholipid extract or an equivalent mixture of synthetic surfactants, the adhesive force was reduced by 79 +/- 4% for albumin and 55 +/- 4% for globulin. As a 0.1% liposomal suspension, PC gave 55% release with albumin. Reversible bonding of the lumen of lymph vessels by the "tacky" proteins present is discussed as a possible factor contributing to the large changes in flow resistance known to occur in the pulmonary lymphatic system.

Cooling gradients and formation of gaseous microemboli with cardiopulmonary bypass: an echocardiographic study.

BACKGROUND: Previous studies demonstrated gas emboli formation during rewarming from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded a critical threshold. It also has been suggested that formation of arterial gas emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patient's blood. The purpose of this study was to determine under what circumstances gas emboli formation would occur during cooling on cardio-pulmonary bypass. METHODS: Eight anesthetized mongreal dogs were placed on cardiopulmonary bypass using a roller pump, membrane oxygenator, and arterial line filter. For emboli detection, we positioned a transesophageal echocardiographic probe at the aortic arch distal to the aortic cannula and Doppler probes at the common carotid artery and the arterial line. Cooling gradients between normothermic blood and cooled arterial perfusate of 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 0 degree C (isothermal controls) were investigated. In addition to preestablished temperature gradients, we investigated the effect of rapid cooling (maximal flow through the heat exchanger at a water bath temperature of 4 degrees C) after the initiation of normothermic cardiopulmonary bypass. RESULTS: Minimal gas emboli were detected at the aortic arch at gradients of 10 degrees C or greater. The incidence of emboli was related directly to the magnitude of the temperature gradient (p < 0.01). No emboli were detected at the carotid artery. During rapid cooling, no emboli were observed either at the aorta or at the carotid artery. CONCLUSIONS: Cooling gradients of 10 degrees C or greater may be associated with gas emboli formation, but they may be of limited clinical significance because no emboli were detected distal to the aortic arch. During the application of rapid cooling, no emboli formation was observed.

Effect of the Trendelenburg position on the distribution of arterial air emboli in dogs.

We examined the effects of buoyancy on the distribution of arterial gas bubbles using in vitro and in vivo techniques in dogs. A simulated carotid artery preparation was used to determine the effects of bubble size and vessel angle on the velocity and direction of bubble movement in flowing blood. Because buoyancy tends to float bubbles away from dependent areas, bubble velocity would be expected to decrease as the vessel angle increased. We found that larger bubbles increased in velocity in the same direction as the blood flow at 0-, 10-, and 30-degree vessel angles and decreased when the vessel was positioned at 90 degrees. Smaller bubbles did not change velocity from 0 to 30 degrees and increased in velocity in the same direction as blood flow at 90 degrees. In 10 anesthetized dogs, we studied the effects of 0-, 10-, 15-, and 30-degree Trendelenburg's position on carotid artery distribution of gas bubbles injected into the left ventricle or ascending aorta. Regardless of the degree of the Trendelenburg position, the bubbles passed into the carotid artery simultaneously with passage into the abdominal aorta. We conclude that the forces of buoyancy do not overcome the force of arterial blood flow and that the Trendelenburg position does not prevent arterial bubbles from reaching the brain.

Magnetic resonance imaging of hyperbaric oxygen treated rats with spinal cord injury: preliminary studies.

Magnetic resonance imaging (MRI) has been performed to assess the efficacy of hyperbaric oxygen (HBO) treatment on experimental spinal cord injury in a rat animal model. A moderately severe injury, similar to Type III injury seen in humans (Kulkarni et al. Radiology 164:837;1987) has been chosen for these studies. An improvement in the neurologic recovery (based on Tarlov scale) has been observed following HBO treatment over a period of 72 hr. Based on MRI, HBO treatment appears to arrest the spread of hemorrhage and resolve edema.

Delayed presentation of cerebral arterial gas embolism following proven intraoperative venous air embolism.

We describe the case of a 33-year-old woman who suffered a delayed-onset arterial gas embolism following a significant venous air embolism during surgery to remove an acoustic neuroma. We report the management of the problem and discuss the mechanisms by which this event might have occurred.

Role of lung surfactant in cerebral decompression sickness.

Five dogs have been embolized by air infusion into the venous system, then sacrificed and the pulmonary vasculature isolated by ligatures while ventilation was maintained for a further hour. In a sixth animal, the embolization was omitted. The lungs were back-perfused with plasma from the same dog and successive aliquots of the back-flushings analysed by thin-layer chromatography (TLC), each spot being removed for phosphorus determination. The results showed that the major lipid component was the phosphatidyl cholines, while lysophosphatidyl cholines, phosphatidyl ethanolamines, and sphingomyelins were also identified in significant quantities. A phosphorus balance for the lungs showed a significant migration of phospholipids from the tissue into pulmonary blood, phosphatidyl cholines increasing by a factor of 10.6. This migration of surfactant is discussed as an important factor in determining whether trapped pulmonary air emboli are released into the arterial system when their surface area is reduced by pressurization, suggesting that recompression should not be too rapid.

Pulmonary hemodynamics, extravascular lung water and residual gas bubbles following low dose venous gas embolism in dogs.

Pulmonary hemodynamic responses, extravascular lung water and bubble longevity times were studied in halothane anesthetized dogs receiving low dose venous gas infusions. Dogs in one group (23.3 +/- 4.3 kg, n = 6) were embolized with air (0.05 ml.kg-1.min -1) for 60 min followed by a recovery period lasting 70 min. During the recovery the ventilatory gases were intermittently switched from nitrogen (68-69%)/oxygen (30%) to nitrous oxide (68-69%)/oxygen (30%) to expand any residual pulmonary vascular bubbles. Subsequent changes in pulmonary artery pressure, pulmonary vascular resistance, end-tidal carbon dioxide and arterial carbon dioxide tensions were used to indicate the presence of remaining bubbles that would have expanded in volume with the nitrous oxide ventilation. This embolization sequence was repeated three times to simulate repetitive exposure of the pulmonary circulation to venous gas emboli. In a second group of dogs (20.2 +/- 2.7 kg, n = 8) the venous gas infusions (0.05 ml.kg-1.min-1) were continuous for 180 min, followed by recovery with intermittent nitrous oxide/oxygen challenges to determine bubble longevity. Pulmonary hemodynamic and carbon dioxide data were significantly changed from baseline following each embolization. These differences as well as the development of extravascular lung water (edema formulation) were not significant when comparisons were made between the Repetitive gas embolism group after 180 min. Residual pulmonary vascular bubbles were indicated (mean +/- S.E.M.) 26.9 +/- 2.3 min following the 180 min Continuous venous gas infusion and 39.5 +/- 5.3, 46.4 +/- 5.0 and 55.5 +/- 4.4 min, respectively, following the three 60 min Repetitive venous gas infusions.

Use of a disposable carbon dioxide detector with emergency intubation in a hyperbaric chamber.

Emergency intubation in a hyperbaric chamber can be complicated by the confined space, inadequate lighting and high levels of background noise. Inadvertent esophageal intubation may be difficult to recognize in these conditions. In more controlled settings such as the operating room, the detection of end-tidal carbon dioxide is the standard procedure for verifying proper placement of the endotracheal tube. Within a hyperbaric chamber, a capnograph may not be readily available for this purpose. We present a case report describing the use of a simple disposable colorimetric carbon dioxide detector for rapid verification of endotracheal tube position following emergency intubation in a hyperbaric chamber.

Cardiovascular pressures with venous gas embolism and decompression.

Venous gas embolism (VGE) is reported with decompression to a decreased ambient pressure. With severe decompression, or in cases where an intracardiac septal defect (patent foramen ovale) exists, the venous bubbles can become arterialized and cause neurological decompression illness. Incidence rates of patent foramen ovale in the general population range from 25-34% and yet aviators, astronauts, and deepsea divers who have decompression-induced venous bubbles do not demonstrate neurological symptoms at these high rates. This apparent disparity may be attributable to the normal pressure gradient across the atria of the heart that must be reversed for there to be flow patency. We evaluated the effects of: a) venous gas embolism (0.025, 0.05 and 0.15 ml.kg-1.min-1 for 180 min.); b) hyperbaric decompression; and c) hypobaric decompression on the pressure gradient across the left and right atria in anesthetized dogs with intact atrial septa. Left ventricular end-diastolic pressure was used as a measure of left atrial pressure. In a total of 92 experimental evaluations in 22 dogs, there were no reported reversals in the mean pressure gradient across the atria; a total of 3 transient reversals occurred during the peak pressure gradient changes. The reasons that decompression-induced venous bubbles do not consistently cause serious symptoms of decompression illness may be that the amount of venous gas does not always cause sufficient pressure reversal across a patent foramen ovale to cause arterialization of the venous bubbles.

Effects of hyperbaric hyperoxia on cardiac and regional hemodynamics in conscious dogs.

BACKGROUND: Although evidence of systemic vasoconstriction has been reported both in animal models and in humans, the regional hemodynamic effects of hyperbaric hyperoxia have not been well characterized. METHODS: In the present study, we report the effects of hyperoxia (normobaric and hyperbaric) on simultaneous measurements of cardiac and regional hemodynamics in the chronically instrumented conscious dog. RESULTS: Hyperbaric hyperoxia (202 kPa) produced significant decreases in heart rate (12%) and cardiac output (20%) and a significant increase in systemic vascular resistance (30%). Carotid artery blood flow decreased significantly (18%) whereas coronary, hepatic, renal and mesenteric flows remained unchanged. CONCLUSIONS: Our data show that the hyperoxic vasoconstriction is limited to the cerebral and peripheral vascular beds. Additionally, blood flow to major organs is well preserved in the face of hyperoxia-induced decreases in cardiac output. Consequently, we postulate that a redistribution of blood flow from peripheral vascular beds (e.g., skin, muscle, bone) to major organs occurs during hyperbaric hyperoxia.

Doppler detection of decompression bubbles with computer assisted digitization of ultrasonic signals.

Precordial Doppler ultrasonic monitoring is routinely used for detection of venous gas bubbles resulting from decompression in hypobaric or hyperbaric applications. Bubble scoring codes have been devised in an attempt to quantify the number of audible bubble signals heard over the background sounds of the cardiac cycle. The audio interpretation of these ultrasonic backscatter signals remains the most common method for decompression evaluation. We report on the use of an inexpensive, commercially available audio digitizer in conjunction with a personal computer to digitize Doppler bubble signals for visual and electronic evaluation. This device can be operated simultaneously with Doppler audio monitoring. Precordial and arterial Doppler recordings of gas bubbles were obtained from anesthetized dogs after intravascular infusion or following decompression. Additional evaluations were conducted on Doppler bubble recordings obtained from human decompression studies. The device can be used in real-time or for later signal analysis. Accompanying menu-driven software provides for numerous signal modification options and visual displays. This device can provide a simultaneous visual display of Doppler signals normally only available for audio evaluation.

Patent foramen ovale and hypobaric decompression.

Gas microbubbles were detected in the left ventricle of a supine subject being screened for an atrial septal defect as a participant of a hypobaric decompression study. This determination was made using the saline echocontrast procedure. We found provocation by a Valsalva maneuver not to be necessary in this individual for right-to-left passage of contrast microbubbles into the left heart and middle cerebral artery. When this same individual underwent hypobaric decompression to a simulated altitude of 21,000 ft, numerous gas microbubbles were detected in the right heart, but no gas bubbles were detected in either the left ventricular outflow tract or in the middle cerebral artery. This observation appears to be a novel finding, not previously reported.

Venturi vacuum systems for hypobaric chamber operations.

Physiological studies of the effects of high altitude on man often require the use of a hypobaric chamber to simulate the reduced ambient pressures. Typical "altitude" chambers in use today require complex mechanical vacuum systems to evacuate the chamber air, either directly or via reservoir system. Use of these pumps adds to the cost of both chamber procurement and maintenance, and service of these pumps requires trained support personnel and regular upkeep. In this report we describe use of venturi vacuum pumps to perform the function of mechanical vacuum pumps for human and experimental altitude chamber operations. Advantages of the venturi pumps include their relatively low procurement cost, small size and light weight, ease of installation and plumbing, lack of moving parts, and independence from electrical power sources, fossil fuels and lubricants. Conversion of three hyperbaric chambers to combined hyper/hypobaric use is described.

Cardiovascular deconditioning and venous air embolism in simulated microgravity in the rat.

BACKGROUND: Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. HYPOTHESIS: The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. METHODS: Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. RESULTS: Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. CONCLUSIONS: These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

Transesophageal echocardiographic study of decompression-induced venous gas emboli.

Transesophageal echocardiography was used to evaluate venous bubbles produced in nine anesthetized dogs following decompression from 2.84 bar after 120 min at pressure. In five dogs a pulsed Doppler cuff probe was placed around the inferior vena cava for bubble grade determination. The transesophageal echo images demonstrated several novel or less defined events. In each case where the pulmonary artery was clearly visualized, the venous bubbles were seen to oscillate back and forth several times, bringing into question the effect of coincidental counting in routine bubble grade analysis using precordial Doppler. A second finding was that in all cases, extensive bubbling occurred in the portal veins with complete extraction by the liver sinusoids, with one exception where a portal-to-hepatic venous anastomosis was observed. Compression of the bowel released copious numbers of bubbles into the portal veins, sometimes more than were released into the inferior vena cava. Finally, large masses of foam were routinely observed in the non-dependent regions of the inferior vena cava that not only delayed the appearance of bubbles in the pulmonary artery but also allowed additional opportunity for further reaction with blood products and for coalescence to occur before reaching the pulmonary microcirculation. These novel observations are discussed in relation to the decompression process.

Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury.

Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.