Effects of high ambient pressure on resistance to anoxia in mice.
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35S-thiopental 15 mg/kg and 14C-diazepam 5 mg/kg were injected intravenously in separate groups of rats (n = 6) at 1 ATA air and at 71 ATA air-He. Total radioactivity was measured in the brain, liver, kidney, muscle and fat after 1, 3, 5 and 15 min. The thiopental content was significantly reduced at pressure in the brain at 3, 5 and 15 min. The diazepam content of the brain was significantly reduced at pressure at 1, 5 and 15 min. The liver, muscle and kidney tissue generally contained slightly less of either drug at pressure, particularly at the earliest sampling times.
During simulated hyperbaric saturation diving experiments of He-O2 mixture at the depths of 150, 180 and 230 m the standard polysomnography of four divers, as well as their subjective feelings of fatigue, were recorded for 268 nights. In all three diving conditions, during the bottom period and the decompression period, wakes after sleep onset and Stage 1 sleep increased while Stage 4 sleep decreased. In deeper diving conditions stage 4 sleep tended to decrease and subjective feelings of fatigue increased. When the results are considered it can be assumed that the deeper the diving depths, the increased sleep disturbances and fatigue. However, it is believed that a fundamental sleep pattern will be maintained.
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Respiratory sinus arrhythmia (RSA) has been used as a non-invasive estimate of vagal tone to determine whether the reduction in resting heart rate commonly seen when humans are exposed to increases in the ambient pressure is associated with changes in vagal autonomic control. Two sets of divers (n = 4) were examined during two simulated saturation dives, one to 46 atmospheres absolute (ATA) and another to 37 ATA. A significant reduction in resting heart rate was seen in both dives upon exposure to high pressure compared with controls at 1 ATA. The reduction in heart rate seen at increased pressure was consistent regardless of respiratory rate, indicating that moderate changes in respiratory rate do not affect heart rate under these conditions. No changes in the overall magnitude of RSA were observed over a range of respiratory rates during either dive compared with control values at 1 ATA. During both dives, RSA was significantly larger (P < 0.05) at low respiratory rates compared with higher rates for both 1 ATA controls and at high pressure. The presence of a hyperbaric bradycardia strongly suggests that vagal tone is altered during hyperbaric exposure; however, the lack of change in the magnitude of RSA at high pressure brings into question the viability of using RSA as an accurate indicator of vagal tone and this lack of correspondence deserves further investigation.
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.
During certain treatments of decompression sickness following dives made with compressed air, the U.S. Navy advocates breathing helium-oxygen mixtures. However, stable nitrogen bubbles created within gelatin by decompression have been found to enlarge when the atmosphere was switched from nitrogen to helium without changing ambient pressure. This suggests that decompression sickness would be worsened by switching from nitrogen to helium in the breathing gas mixture.
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Normal men have been found to develop pruritus and gas bubble lesions in the skin, and disruption of vestibular function, when breathing nitrogen or neon with oxygen while surrounded by helium at increased ambient pressure. This phenomenon, which occurs at stable ambient pressures, at 1 or many ATA, has been designated the "isobaric gas counterdiffusion syndrome." In a series of analyses and experiments in vivo and in vitro the cause of the syndrome has been established as due to gas accumulation and development of gas bubbles in tissues as a result of differences in selective diffusivities, for various respired and ambient gases, in the tissue substances between capillary blood and the surrounding atmosphere. The phenomenon here described in man is an initial stage of a process shown later in animals to progress to continuous, massive, lethal, intravascular gas embolization.
Anesthesia produced by the intravenous steroid agent, Althesin, was studied in Sprague-Dawley rats with and without high pressure of helium gas up to 100 atmospheres absolute (ATA). There were no cumulative or adaptive changes in Althesin requirement at normal pressures over 6-h periods. However, the apparent potency of the agent was reduced by 43% by the addition of 68 ATA helium. Subanesthetic doses of Althesin protected against the onset of convulsions and coarse tremors associated with the high pressure neurological syndrome. It is concluded that the steroid anesthetics may have a place in human diving technology and that the mechanisms associated with the anesthetic-pressure interactions are consistent with the critical volume or lipid bilayer fluidity hypothesis.
The interactions of phenobarbital, barbital, and pentobarbital with high pressures of heliox were explored. Principal features of the complex results include: double peaks in the time course of convulsion thresholds (Pc); an early peak and a shoulder in the time course of pressures reversing anesthesia (Pa); far steeper dose-response curves for Pa than for Pc; selectively greater anticonvulsant effect for phenobarbital than for the other barbiturates; and enhancement of Pa with simultaneous depression of Pc by reserpine in phenobarbital-pretreated mice. The data indicate the existence of at least two discrete sites of interaction between barbiturates and high pressure, reflected by Pc and Pa. The implications of the data for the development of biophysical theories of pressure reversal of anesthesia and anti-high-pressure neurological syndrome action of anesthetics are discussed, together with implications for the experimental study of convulsant and anticonvulsant agents, and their applications to underwater physiology.
Transpulmonary pressure, lung volume, and flow rate were recorded in two healthy subjects performing graded exercise between 1 and 10 ATA. At simulated depths greater than 4 ATA, exercise was terminated by severe choking dyspnea at levels of work, oxygen consumption, heart rate, and ventilation significantly lower than during maximum exercise at 1 ATA. Comparison of exercise ventilatory mechanics with corresponding maximum expiratory flow-volume and expiratory isovolume pressure-flow (IVPV) curves demonstrated that the reduced aerobic capacity was associated with expiratory flow limitation. We conclude that dynamic airways compression limited aerobic capacity at these depths by causing a persistent cough making it seem difficult to continue exercise. Analysis of the IVPV curves suggested that maximum expiratory flow was reduced at depth below the rate allowing adequate exercise ventilation because increased gas density raised the resistance downstream from equal pressure points. At each level of sumbaximal exercise, end-expiratory position and alveolar CO2 tension increased with ambient pressure due primarily to the density dependence of airways resistance. In these respects, healthy subjects breathing dense gas resemble patients with obstructive lung disease.
Experiments were designed to partition the effect of inspired oxygen tension (PIO2), gas density (rho), and ambient pressure (P) at rest and during exercise in rats. At rest oxygen uptake (VO2) was reduced by 19.5% (P less than 0.01) in 3 ATA air and by 32.1% (P less than 0.01) in 10 ATA air from 1 ATA air control of 29.3 +/- 1.21 (SE) ml/min.kg; there was no difference in VO2 between 1, 3, and 10 ATA He mixtures containing 20% O2. During exercise, VO2 was depressed by 36.2% (P less than 0.01) in 3 ATA air from 1 ATA air value of 55.3 +/- 3.23 ml/min.kg; VO2 was unaffected in 3 ATA He containing 20% O2 as compared to that of 46.5 +/- 2.43 ml/min.kg at 1 ATA He-O2 ambient. These VO2 values were compared to that obtained from normoxic ambients for separation of effects of elevated PIO2, P, and rho on VO2 at rest and during exercise. The effect of PIO2 was deduced by comparing VO2 in normoxic and hyperoxic He and N2 at a given P and rho. The density effect was obtained by comparing the VO2 in various densities at a given P and PIO2. The P effect was obtained by comparing the VO2 in various ambient pressures at a given rho and PIO2. Summation of the effects of P, rho, and PIO2 sufficiently approximates the changes in VO2 at rest. The same procedure underestimates the actually measured VO2 in all N2 ambients.
Intact rats exposed for 30 days to various levels of simulated altitude from 12,000 (3,658 m) to 20,000 ft (6,096 m) showed a sharp increase in circulating red blood cells in reticulocytes, and in spleen-to-body weight ratios above 15,000 ft (4.572 m). Nucleated erythrocytes in splenic section increased significantly at 18,000 ft (5,486 m), but not at 12,000 ft. Acute splenectomy 1 day before killing sharply reduced the reticulocyte counts at 18,000 and 20,000 ft, but the red cell counts were not reduced at any altitude by the operation. Indeed, at 18,000 ft the splenectomy significantly increased the degree of polycythemia. With altitude exposure the spleen but not the liver or the bone marrow showed an increased 59Fe uptake that was related to the degree of hypoxia. These results suggest that the rat spleen of the present strain carries the full load of the erythropoietic effort in response to a hypoxic stimulus, and that it may exert an inhibitory influence on any extraerythropoietic effort by the bone marrow. In intact rats returned from 18,000 ft to sea level, the reticulocytosis is reversed much more slowly than it is in splenectomized rats, suggesting the presence of a persistent stimulus initiated by hypoxia or a committed pool of reticulocyte precursors.