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Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

Advantageous and/or detrimental influences associated with purposeful deviations from atmospheric levels of O2 and CO2 are studied. Specific goals have been directed to simulating situations of emergency or accidental exposure to hypoxic (10% O2) environments. They included establishing dynamic effects of hypoxia with and without CO2 (rate of acute adaptation), and stable-state (equilibrium) effects on blood and brain oxygenation. They also included effects on the physiological parameters of respiration and blood gas composition which underlie brain oxygenation. For 10% O2, a complete experiment consisted of three identical rest-exercise phases of 32 minutes duration. Following a five minute air control period, each inspired gas was administered over the next 27 minutes. The test gases were room air control, 10% +/- 0.1% O2 with 4% +/- 0.1% CO2, and 10% +/- 0.1% O2. A minimum of 45 minutes separated each phase. Relative to inspiration of 10% O2, brain oxygenation is enhanced by addition of 4% CO2. This is accomplished by increasing the rate at which O2 in arterial blood is supplied to the brain circulation (well above even the normoxic level), and on relative improvement in the arterial pressure of O2.

A complete description of pulmonary measurements obtained after continuous O2 exposure of 13 healthy men at 3.0 ATA for 3.5 h is presented. Measurements included flow-volume loops, spirometry, and airway resistance(n = 12); CO diffusing capacity (n = 11); closing volumes (n= 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). The average difference in maximum mid expiratory flows at 50 percent vital capacity on air and HeO2 was found to be significantly reduced postexposure by 18 percent. Raw and CO diffusing capacity were not changed postexposure. It is concluded that the relatively large change in forced expiratory flow at 25-75 percent of vital capacity compared with the mean forced expiratory volume in 1 s, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow.

Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

Selected results of cardiocirculatory measurements in healthy volunteers who breathed 100 percent O2 continuously at 3.0 ATA for up to 3.5 hr, at 2.5 ATA for up to 6.0 hr, at 2.0 ATA for up to 11.9 hr, and at 1.5 ATA for up to 19.0 hr are reported. The results indicate that resting hemodynamic responses to prolonged hyperbaric oxygen breathing in man usually consist of small deviations from normal sea-level responses. Rapid onset of bradycardia occurred at all four oxygen pressures investigated. This effect was accompanied by a rate-dependent reduction in cardiac output and a degree of systematic vasoconstriction which were small in magnitude and appeared to be functionally unimportant.

Oxygen effects on pulmonary function were measured in normal, resting men who breathed oxygen continuously at 3.0, 2.5, 2.0, and 1.5 ATA to predefined limits of CNS, cardiac, or pulmonary tolerance. Rates of pulmonary symptom intensification and decrease in vital capacity (VC) increased progressively with elevation of inspired oxygen pressure. Although VC decrements occurred concurrently with symptoms, the lung volume changes became prominent when symptoms were still mild. The observed effects were consistent with the interpretation that small airway function is impaired more selectively by oxygen exposure at 3.0 and 2.5 ATA than by exposure at 2.0 and 1.5 ATA. Despite similar VC changes after oxygen exposure at 2.0 ATA for nearly 10 hr and exposure at 1.5 ATA for almost 18 hr, the 2.0 ATA exposure caused greater impairment of pulmonary function and required a longer recovery period.

The overall goals, design, and procedures of Predictive Studies V are discussed as well as the specific elements of neural effects produced by prolonged hyperoxia. It is noted that Predictive Studies V study of oxygen poisoning in normal men during uninterrupted exposures to oxygen over the range of hyperbaric oxygen exposure most useful in diving, the treatment of gas lesion diseases, and general hyperbaric medicine. It is found that, throughout the study, the most striking observations were related to effects on visual function, on the lung, and the probable interactions of preconvulsive neural activity with effects on cardiovascular and respiratory-pulmonary functions.

The ventilation (V), end-tidal PCO2 (PACO2), and CO2 elimination rate were determined in men at rest breathing CO2-free gas over the pressure range 1-50 ATA and the gas density range 0.4-25 g/l, during slow and rapid compressions, at stable elevated ambient pressures and during slow decompressions. Progressive increase in pulmonary gas flow resistance due to elevation of ambient pressure and inspired gas density to the He-O2 equivalent of 5000 feet of seawater was found to produce a complex pattern of change in PACO2. It was found that as both ambient pressure and pulmonary gas flow resistance were progressively raised, PACO2 at first increased, went through a maximum, and then declined towards values near the 1 ATA level. It is concluded that this pattern of PACO2 change results from the interaction on ventilation of the increase in pulmonary resistance due to the elevation of gas density with the increase in respiratory drive postulated as due to generalized central nervous system excitation associated with exposure to high hydrostatic pressure. It is suggested that a similar interaction exists between increased gas flow resistance and the increase in respiratory drive related to nitrogen partial pressure and the resulting narcosis.

Experiments which exposed men in chambers, breathing helium with oxygen, to progressive increases of pressure equivalent to 400-800-1200-1600 feet of sea water (fsw) were conducted. Rates of compression and exposure to stable high pressure. Goals included: 1) determination of the specific character and time course of onset of physiological and performance decrements during the intentionally rapid compressions, and determination of rates of adaptation on reaching stable elevated pressure; 2) investigation of accelerated methods for decompression in deep saturation excursion diving; and 3) determination of competence in practical work performed in water at pressures equivalent to the extreme diving depths of 1200 and 1600 fsw.