Plasma volume and estimated liver plasma flow during hyperbaric and hyperoxic exposures in awake dogs.

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.

Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.

Pharmacokinetics of pentobarbital under hyperbaric and hyperbaric hyperoxic conditions in the dog.

High hydrostatic pressure has been shown to reverse the anesthetic effects of barbiturates. However, attempts to distinguish between two possible causes of this reversal, changes in drug disposition or changes in drug-receptor interaction, have not been reported. This study examined the possible effects of hyperbaria and hyperbaric hyperoxia on the distribution and clearance of pentobarbital in the dog. The drug was administered to six mixed-breed dogs as a 30 mg/kg i.v. bolus at 1 ATA breathing air, 6 ATA breathing air, and 2.8 ATA breathing 100% oxygen, with serial blood sampling for 12 h. Pharmacokinetic and statistical analyses showed no significant effects of hyperbaria or hyperbaric hyperoxia on the total plasma clearance, volume of distribution or elimination half-life. If pressure reversal of barbiturate anesthesia occurs at these pressures, changes in the disposition of the drug are not the causative factors.

Salicylate pharmacokinetics in the dog at 6 ATA in air and at 2.8 ATA in 100% oxygen.

Hyperbaric air and hyperbaric hyperoxia, which have been shown to decrease both liver plasma flow and plasma volume in dogs, may potentially affect the disposition of drugs whose distribution and/or elimination are dependent upon those actions. This study examined the effects of those conditions on the disposition of salicylic acid, using the dog as a model. The drug was administered to six mixed-breed dogs as a 10 mg sodium salicylate/kg i.v. bolus at 1 ATA breathing air (control), at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, followed by serial blood sampling for 8 h. Statistical analysis showed a significant increase (p less than 0.05) in salicylate clearance at 2.8 ATA compared to control with a subsequent, although not statistically significant, increase in elimination half-life. There were no significant differences between the values observed at 6 ATA and either control or 2.8 ATA. As 100% O2 at 2.8 ATA is used during hyperbaric oxygen medical therapy and during decompression, this change in disposition of this commonly used agent may have implications in man. Studies in man must be conducted, however, to determine if the same conclusions apply.

Hemodynamic effects of lactated Ringer's solution on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After allowing 5-7 d for recovery the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg) and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. Enough lactated Ringer's solution was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. There were statistically significant differences in some of the measured parameters due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of lactated Ringer's solution.

Drug disposition under hyperbaric and hyperbaric hyperoxic conditions: meperidine in the dog.

Patients being treated for a variety of conditions with hyperbaria or hyperbaric hyperoxia, and ill or injured deep sea divers being decompressed, may require concomitant drug therapy. This study examined the possible effects of those conditions on the distribution and elimination of meperidine, using the dog as a model. The drug was administered to six mixed-breed dogs as a 1.4 mg/kg i.v. bolus at 1 ATA breathing air, at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, and followed by serial blood sampling for 3 h. Statistical analysis showed no effects of hyperbaria or hyperbaric hyperoxia on the elimination half-life, total plasma clearance, or volume of distribution. These studies demonstrated marked differences between man and the dog in the elimination of meperidine. This probably means these results cannot be extrapolated to man.

Hemodynamic effects of Dextran 40 on hemorrhagic shock during hyperbaria and hyperbaric hyperoxia.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After 7-10 d, dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg), and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Pressure was maintained between 40-50 mm Hg for 30 min. Enough Dextran 40 was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. More than twice the amount of Dextran 40 was required at depth than at 1 ATA. There were statistically significant differences due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of Dextran 40.

An evaluation of plasma volume expanders in the treatment of decompression sickness.

Each of 29 goats was instrumented with an ultrasonic flowmeter transducer around the left common carotid artery and a silastic catheter in the anterior vena cava. Following recovery from the surgery the goats were subjected to a dive protocol designed to elicit symptoms of decompression sickness (DCS). The goats were returned to the surface and, following a 20-min observation period, were either left untreated (controls) or treated with one of five different plasma volume expanders. The plasma volume expanders were evaluated based on their ability to decrease the severity of DCS and the number of arterial bubbles that could be counted. Analysis of the results shows that all of the five plasma volume expanders used appeared to reduce the severity of the signs of DCS and to decrease the number of arterial bubbles detected but that these tendencies were not statistically significantly except for Mannitol and Dextran 40. Animals that did not develop arterial bubbles tended to respond better to fluid therapy than did those that did develop bubbles.

Theophylline pharmacokinetics during hyperbaria and hyperbaric hyperoxia in the dog.

The effect of hyperbaria and hyperbaric hyperoxia on the disposition kinetics of theophylline were investigated in the dog. The drug was administered as a 5 mg/kg iv bolus at 1 atmospheres absolute (ATA), 2.8 ATA and 6 ATA. Serial blood samples were collected over an eight hour period and analyzed for theophylline concentration using a gas chromatographic method. From the resultant data, elimination half-life, volume of distribution and total body clearance were calculated. There were no apparent effects of hyperbaria or hyperbaric hyperoxia on any of the parameters describing theophylline disposition, implying that, in the animal model studied, distribution, elimination and effect should remain constant.

Therapeutic effects of hyperbaric oxygen and dimethyl sulfoxide following spinal cord transections in rats.

Thirty adult, male, Long-Evans hooded rats underwent spinal cord transections at the T5 vertebral level. Following surgery, animals were separated into three groups: Group I received only normal postoperative care; Group II received daily hyperbaric oxygen (HBO) treatments for 47-54 consecutive days; Group III received the same HBO treatment as Group II in addition to subcutaneous injections of dimethyl sulfoxide (DMSO) for 10 consecutive days. All animals were killed 60-70 days postlesion. The lesioned area of spinal cord was removed and prepared for light and electron microscopy. Group I animals showed typical scar reduction of cavitations, increased scarring, and more nerve fibers within the lesion. Three animals in this group exhibited coordinated hindlimb movement, with one animal showing weight-bearing ability. The lesion sit in group III animals revealed a reduction in collagen formation and a further increase in the number of nerve fibers. Six animals in Group III showed coordinated hindlimb movements; among these two displayed weight-bearing ability and sensory return.

Hyperbaric oxygen and corneal incision healing.

Corneal incision healing in the presence of daily or twice daily exposures to hyperbaric oxygen was compared in dogs to the natural course of such healing. Exposures lasted for 90 min and consisted of 60% oxygen administered at 60 fsw, an oxygen exposure of 2 ATA. Twenty corneas received such exposure, and 20 corneas were allowed to heal under natural conditions. Eyes were enucleated between 5 and 56 days after incision. The corneas were studied by gross observation and light microscopy. Uncomplicated and essentially comparable healing of the incisions occurred. There was a suggestion that superficial central clearing of the incision opacity occurred more quickly in the hyperbaric oxygen series.

Susceptibility of fetal sheep to acute decompression sickness.

Studies were conducted to determine the susceptibility of the fetus to decompression sickness. Sheep were used because fetal and maternal circulation of sheep and human placentas are dynamically similar. Seven sheep that were within three weeks of parturition were used. A Doppler ultrasonic transducer was placed around an umbilical artery of the fetus in utero and the electrical leads were exteriorized. Umbilical artery blood flow could thus be monitored together with any bubbles appearing in that part of the fetal circulation. Results of 17 dives showed that exposing the mother to a 100-fsw, 25-min standard no-decompression dive produced massive air emboli in the fetus, though no bubbles were detected in the maternal circulation either by Doppler or visual inspection. An 80-fsw dive for 40 min caused an occasional bubble to appear in the fetus. Sixty-fsw dives for 60 and 70 min, respectively, did not produce bubbles in the fetal circulation.

Radio telemetry system for obtaining body temperature during simulated diving to 1000 FSW.

An implantable radio telemetry system for transmitting deep body temperatures from dogs subjected to hyperbaric conditions was designed and tested. The design was adapted from a transmitter described by J. L. Riley, and was successfully tested both in vitro and in vivo to a simulated depth of 1000 FSW. Circuit schematic, printed circuit layout, and component layout are given.

Hyperbaric hydrogen therapy: a possible treatment for cancer.

Hairless albino mice with squamous cell carcinoma were exposed to a mixture of 2.5 percent oxygen and 97.5 percent hydrogen at a total pressure of 8 atmospheres for periods up to 2 weeks in order to see if a free radical decay catalyzer, such as hydrogen, would cause a regression of the skin tumors. Marked aggression of the tumors was found, leading to the possibility that hyperbaric hydrogen therapy might also prove to be of significance in the treatment of other types of cancer.