Cerebral Blood Flow and Metabolic Responses to Sustained Hypercapnia in Awake Sheep

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Abstract
This investigation determined the effects of sustained hypercapnia on cerebral blood flow (CBF; radiolabeled microspheres), cerebral metabolic rates for O2 and glucose (CMRO2 and CMRglc), and brain water content in conscious sheep instrumented with aortic, left ventricular, vena cava, and brain sagittal sinus catheters. PaCO2 was elevated from 38 ± 3 to 53 ± 3 (mean ± SD) mm Hg and PaO2 from 109 ± 7 to 131 ± 4 mm Hg for 96 h in an environmental chamber. Hypercapnia did not alter sheep behavior, food and water intake, arterial pressures, core temperature, or brain lactate release. Total and regional CBF and CBF/CMRO2 reached peak values at 1 h and then readjusted, to stabilize at lower, but still elevated levels at 24 h and thereafter. CMRO2 and CMRglc increased at 6 h and thereafter during hypercapnia. PaCO2, CBF, CMRO2, and CMRglc remained elevated at 3 h after restoration to room air, while CBF/CMRO2 returned to the control value. Frontal and occipital lobe wet-to-dry weight ratios increased modestly but significantly after hypercapnic exposure. It is concluded that sustained hypercapnia induces stable and nonadapting increases in both CBF and brain metabolism that persist for at least 3 h after restoration to room air in association with hypoventilization and modest elevations of brain water.