On the regulation of the blood supply to the brain: old age concepts and new age ideas.

THE CRITICAL IMPORTANCE of cerebral blood flow (CBF) control was reported in 1890 in a landmark publication by Roy and Sherrington (15). Although the concept was not fully accepted until confirmed by more sophisticated methods of CBF assessment, these authors postulated that local changes in cerebral functional activity and perfusion are coupled. In this issue of the Journal of Applied Physiology, Brassard and colleagues (3) add valuable new insight into the fundamental mechanisms that regulate blood supply to the brain. At rest and during progressive elevations in exercise intensity, they examined the influence of acute phenylephrine-induced changes in blood pressure on transcranial Doppler (TCD)-determined middle cerebral artery (MCA) mean blood flow velocity (Vmean) and nearinfrared spectroscopy (NIRS)-derived frontal lobe oxygenation (ScO2). At rest, consistent with another recent report on this topic (7), mean arterial blood pressure (MAP) was increased by 20% and MCA Vmean was increased by 10% at the highest doses of phenylephrine; at these time points, ScO2 was reduced by 7%. However, with progressive increases in exercise intensity, the phenylephrine-induced changes in MCA Vmean and ScO2 were abolished. The authors concluded that phenylephrine leads to a differential influence on CBF and cortical oxygenation and that this effect is abolished by exercise-induced elevations in cerebral metabolic rate. These new findings are important. Clinically, while a 7% reduction in cerebral oxygenation may seem small, a drop of 13% is associated with cerebral ischemia (1). Interestingly, a recent report showed a 14% decrease in ScO2 with the utilization of phenylephrine in hypotensive patients undergoing elective surgery (13). Therefore, the clinical use of phenylephrine to correct for hypotension may actually have a negative impact on brain oxygenation. At a fundamental level, the findings of Brassard et al. (3) challenge us to reappraise basic assumptions related to human CBF control (Fig. 1) and invite new questions to be raised.