Regulation of cerebral blood flow in atherosclerotic monkeys

This study was performed to determine the effects of atherosclerosis on cerebral vascular responses to hypercapnia and hypotension. We studied nine normal and eight atherosclerotic anesthetized cynomolgus monkeys. After 20 mo of an atherogenic diet, the common carotid and internal carotid arteries had fibrofatty lesions with some necrosis and calcification, and intracranial arteries had only fatty streak changes. Base-line cerebral blood flow (measured with microspheres) and vascular resistance were similar in the normal and atherosclerotic monkeys. Thus, despite significant obstruction of large extracranial arteries by atherosclerotic lesions, distal vessels dilated to maintain flow normal. Reduction of mean arterial pressure to 51 ± 7 mmHg in atherosclerotic monkeys and 42 ± 4 mmHg in normal monkeys did not decrease cerebral flow because cerebral vessels dilated to maintain flow constant. Cerebral vasodilator responses to hypercapnia, however, were impaired by atherosclerosis. Cerebral blood flow increased from 40 ± 6 (mean ± SE) to 190 ± 17 ml ⋅ min -1 ⋅ 100 g -1 during hypercapnia (Pa CO2 , = 64 mmHg) in normal monkeys and from 34 ± 2 to 99 ± 20 ml/min (Pa CO2 , = 65 mmHg) in atherosclerotic monkeys. Measurement of regional blood flow indicated that dilator responses in atherosclerotic monkeys were impaired in cerebral gray and white matter, cerebellum, and brain stem. We conclude that, in a primate model of atherosclerosis, maximal cerebral vasodilator responses to hypercapnia are impaired, but during a less pronounced vasodilator stimulus autoregulatory responses to hypotension are preserved.