Inter-individual Relationships between Sympathetic Arterial Baroreflex Function and Cerebral Perfusion Control in Healthy Males

Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.

Cerebral autoregulation can be evaluated by measuring relative blood flow changes in response to a steady-state change in the blood pressure (static method) or during the response to a rapid change in blood pressure (dynamic method). The purpose of this study was to compare the results of the two methods in humans with both intact and impaired autoregulatory capacity. Using intraoperative transcranial Doppler sonography recordings from both middle cerebral arteries, we determined static and dynamic autoregulatory responses in 10 normal subjects undergoing elective surgical procedures. The changes in cerebrovascular resistance were estimated from the changes in cerebral blood flow velocity and arterial blood pressure in response to manipulations of blood pressure. Static autoregulation was determined by analyzing the response to a phenylephrine-induced rise in blood pressure, whereas rapid deflation of a blood pressure cuff around one thigh served as a stimulus for testing dynamic autoregulation. Both measurements were performed in patients with intact autoregulation during propofol anesthesia and again in the same patients after autoregulation had been impaired by administration of high-dose isoflurane. There was a significant reduction in autoregulatory capacity after the administration of high-dose isoflurane, which could be demonstrated using static (P < .0001) and dynamic (P < .0001) methods. The correlation between static or steady-state and dynamic autoregulation measurements was highly significant (r = .93, P < .0001). These data show that in normal human subjects measurement of dynamic autoregulation yields similar results as static testing of intact and pharmacologically impaired autoregulation.