Cerebral blood flow and evoked potentials during Cushing response in sheep

We determined how alterations in systemic hemodynamics, characteristic of the Cushing response, are related to changes in cerebral blood flow (CBF), cerebral metabolic rate of O₂ (CMRO₂), and brain electrical conductive function, as assessed by somatosensory-evoked potentials (SEP) and brain stem auditory-evoked responses (BAER). In three groups of eight pentobarbital-anesthetized sheep, intracranial pressure was gradually elevated to within 50, 25, or 0 mmHg of base-line mean arterial pressure and then held constant for 40 min by intraventricular infusion of mock cerebrospinal fluid. Microsphere-determined CBF fell when cerebral perfusion pressure was <50 mmHg. CMRO₂ fell when CBF fell >30-40%. Mean aortic pressure and cardiac output increased when CBF fell >40%, i.e., at approximately the level at which CMRO₂ fell. Furthermore, the magnitude of the increase in arterial pressure and cardiac output correlated with the reduction of CMRO₂. SEP latency did not increase unless CBF fell >55-65%, corresponding to a 20-30% reduction of CMRO₂. Increased latency of BAER wave V was associated with a fall in midbrain blood flow of >65-70%. Thus increase in SEP and BAER latencies required reductions of flow greater than those required to elicit a systemic response. This demonstrates that there is a range of intracranial pressure over which the increase in arterial pressure preserves sufficient CBF to sustain minimal electrical conductive function. The best predictor of the onset and magnitude of the Cushing response in adult sheep is the decrease in CMRO₂.