This study was designed to determine the role of CO2 in the cerebral hemodynamic, metabolic, and fluid shift responses in a conscious sheep model of acute mountain sickness (AMS). Ewes were instrumented chronically with left ventricular, aortic, inferior vena cava, sagittal sinus, and epidural catheters and exposed to 96 h of hypoxia in an environmental chamber in two groups: 1) hypocapnic [HH; n = 12; arterial PO2 (PaO2) = 40 Torr, arterial PCO2 (PaCO2) = 27 Torr] and 2) eucapnic (EH; n = 9; PaCO2 = 40 Torr, PaCO2 = 37 Torr). AMS, estimated from food and water intakes and behavior, occurred in 9 of 12 HH and 9 of 9 EH sheep. Intracranial pressure (Picp) and the pressure gradient between Picp and sagittal sinus (Psag) increased in AMS sheep only. Total and regional cerebral blood flows, except in the choroid plexus (Qcp), were elevated significantly (P < 0.05) throughout hypoxia in all sheep; cerebral blood flow was greater in EH sheep (P < 0.05). Qcp decreased in HH (P < 0.05) but remained unchanged in EH sheep. Cerebral O2 and glucose uptakes were not altered in either group. Brain edema, reflected by elevated wet-to-dry tissue weight ratios (P < 0.0001), occurred only in AMS sheep. We conclude 1) AMS is associated with cerebral edema and normal brain aerobic metabolism, 2) decreased Qcp and increased Picp-Psag gradients during HH likely compensate the increased intracranial volume in AMS, and 3) CO2 supplementation at constant PaO2 did not reduce AMS, Picp, or brain tissue edema.

Hyperbaric oxygen at pressures of 300 to 500 kPa has been shown to induce changed distribution of cerebral blood flow (QCBF) in rats, in places reducing the supply of the supplementary O2. Thus, in the present study, the effect of hyperoxia at 101 (group 1, n = 9) and 150 (group 2, n = 9) kPa O2 on cerebral blood flow distribution and central haemodynamics was tested in conscious, habituated rats. During the control period the systolic arterial pressure (BPs), heart rate (fc), breathing frequency (fb), cardiac output (Qc), arterial acid-base chemistry and glucose, as well as QCBF distribution (rQCBF) were similar in the two groups of animals. During O2 exposure, the acid-base chemistry remained unchanged. The haemoglobin decreased in group 2, but remained unchanged in group 1. The fc decreased rapidly in both groups during the change in gas composition, after which fc remained constant both in group 1 and in group 2, for whom pressure was increased. The Qc and fb decreased and BPs increased similarly in the two groups. Total QCBF and rQCBF decreased to the same extent in both groups, and the rQCBF changes were equally scattered. In group 1, breathing of pure O2 did not increase the O2 supply to any cerebral region except to the thalamus and colliculi after 60 min, whereas the O2 supply to the hypothalamus decreased and remained low. In group 2, the O2 supply was unchanged compared to the control period in all regions. These findings agree with previous observations during exposures to higher O2 pressures. In air after O2 exposure the acid-base chemistry remained normal. The fc and fb increased to higher levels than during the control period. The BPs remained high. The brain blood flows were increased, inducing elevated O2 supply to several brain regions compared to the control period. In conclusion, O2 supply to the central nervous system was found to be in the main unchanged during breathing of O2 at 101 kPa and 150 kPa.

It is commonly believed that during hyperbaric oxygen (HBO) treatment, in spite of the vasoconstriction induced by the increased O2 content in the breathing gas, the elevated carrying capacity of O2 in the arterial blood results in augmented O2 delivery to tissues. The experiments described here tested the hypothesis that HBO treatment would be more efficient in delivering O2 to poorly perfused tissues if the vasoconstriction induced by elevated O2 could be abolished or attenuated by adding CO2 to the breathing gas. Organ blood flow (QOBF), systemic hemodynamics, and arterial blood gases were measured before, during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2), in awake, instrumented rats. During the HBO exposure the respiratory frequency (fb) fell (4 breaths x min(-1) x 100 kPa O2(-1)), with no changes in arterial CO2 tension (PaCO2), but when CO2 was added, fb and PaCO2 increased. The left ventricular pressure (LVP) and the systolic arterial pressure (SBP) increased. The maximum velocity of LVP (+dP/dt) rose linearly with LVP whether CO2 was added or not (r2 = 0.72 and 0.75 respectively). Similarly, the cardiac output (Qc) and heart rate (fc) fell, while the stroke volume (SV) was unaltered, independent of PaCO2. There was a general vasoconstriction in most organs in both groups, with the exception of the central nervous system (CNS), eyes, and respiratory muscles. HBO reduced the blood flow to the CNS by 30%, but this vasoconstriction was diminished or eliminated when CO2 was added. In group 2, the blood flow to the CNS rose linearly with increased PaCO2 and decreased pH. After decompression fc and SBP stayed high, while Qc returned to control values by reducing the SV; CNS blood flow remained markedly elevated in group 2, while in group 1, it returned to control levels. We conclude that the changes in fc, Qc, LVP, dP/dt, SBP and most QOBF values induced by HBO were not changed by hypercapnia. Blood flow to the CNS decreased during HBO treatment at a constant PaCO2. Hypercapnia prevented this decline. Elevated PaCO2 augmented O2 delivery to the CNS and eyes, but increased the susceptibility to O2 poisoning. A prolonged suppression of O2 supply to the CNS occurred during the HBO exposure and in air following the decompression in the absence of CO2. This suppression was offset by the addition of CO2 to the breathing gas.

Cerebral blood flow (CBF), systemic hemodynamics, and arterial blood gases were measured during control conditions and during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2) in awake rats. The respiratory frequency fell with no change of arterial PCO2 (PaCO2) in group 1, but in group 2, respiratory frequency and PaCO2 increased linearly. The cardiac output (CO) and heart rate (HR) fell and systolic arterial pressure (SAP) rose independent of PACO2. O2 breathing caused CBF to fall by 30% in group 1, whereas CBF rose linearly with the PaCO2 increase and pH decline in group 2. Regional CBF (rCBF) fell in group 1, whereas rCBF rose gradually in all regions in group 2, but the responses varied similarly in both groups. Regional brain O2 supply was unaltered in most areas. However, the O2 supply was possibly reduced in the brain stem in group 1 but markedly increased in group 2. After decompression, HR and SAP were high, whereas CO returned to its control value. CBF and all rCBF levels remained markedly elevated in group 2. In group 1, CBF returned to control levels. By contrast, rCBF and O2 delivery to brain stem regions remained subnormal. In conclusion, the O2-induced changes in HR, CO, and SAP were not influenced by hypercapnia. CBF and rCBF fell despite unaltered PaCO2, whereas hypercapnia prevented these declines. An uneven effect of O2 was observed on rCBF, most pronounced in brain stem regions, independent of the PaCO2. There was a prolonged suppression of O2 supply to brain stem regions both during and after the exposure to O2 in the absence of CO2.

The effect of repeated exposure to ambient pressures of 5 bar (500 kPa), in atmospheres comprising normal partial pressures of oxygen [0.2 bar (20 kPa)] and nitrogen [0.8 bar (80 kPa)] and 4 bar (400 kPa) helium, on cardiac function and morphology was assessed in conscious rats. Ten test rats underwent chamber dives daily for 40 consecutive days, and ten control rats were exposed in the same chamber for an equal period of time, but in air at 1 bar (100 kPa). Cardiac output (Qc) and myocardial blood flow (Qmyocardial) were determined by the microsphere method. After 40 days, the body mass was 7% greater in the control than in the test rats (P < 0.05), although they were given exactly the same amount of standard food. The test rats had a significantly higher (7% absolute, 12% ventricular mass to body mass, P < 0.05) heart mass (left ventricular myocardium, including the ventricular septum) than the control rats. The percentage tissue dry mass of the right and left ventricles was equal in the two groups. Microscopic examination revealed a number of small focal necroses in the left ventricle of the test rats but none in the control rats. The left ventricular pressure (LVP) and the maximum velocity of LVP increase (contractility) and decrease were significantly increased (25%-96%, P < 0.001) in the pre-exposed compared to the control rats at 1 bar (100 kPa). The systolic arterial pressure, heart rate and respiratory frequency were similar in the two groups at 1 bar (100 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)