Upper Limit of Autoregulation of Cerebral Blood Flow in the Baboon

Abstract

The upper limit of autoregulation of cerebral blood flow was studied in ten young baboons. Blood pressure was increased by infusing angiotensin, and cerebral blood flow was measured by the intracarotid 133 xenon injection method. Autoregulation was maintained until blood pressure was 30-40% above resting values. At this blood pressure level, cerebrovascular resistance reached a maximum. Any additional increase in blood pressure resulted in an increase in cerebral blood flow and a decrease in cerebrovascular resistance; this situation is designated the "breakthrough of autoregulation." In four baboons subjected to unilateral sympathetic denervation, autoregulation of cerebral blood flow was studied bilaterally; no difference in the upper limit of autoregulation was found between the intact and the sympathectomized hemisphere. The breakthrough of autoregulation supposedly plays an important role in the pathogenesis of acute hypertensive encephalopathy. The old concept of hypertensive cerebral vasospasm has been revised in recent years, and it is now generally recognized that acute hypertensive encephalopathy is caused by focal overdistention of brain arterioles with lesions of the blood-brain barrier. However, whether this condition is associated with a high cerebral blood flow in the clinical syndrome has not been investigated. KEY WORDSinduced hypertension breakthrough of autoregulation hypertensive encephalopathy cerebrovascular resistance angiotensin 133 xenon clearance• When blood pressure rises, cerebral blood flow is held constant by autoregulatory constriction of the cerebral resistance vessels. Some recent communications have described the existence of an upper limit of autoregulation. When blood pressure rises beyond this limit, autoregulation is exhausted; a forced arteriolar dilation and an increase in cerebral blood flow occur. This situation is called the "breakthrough of autoregulation" (l) and has been observed in hypercapnic dogs (2), in man by the arteriovenous oxygen difference method (3), and, in a limited study, in man by the intracarotid criticism because of the unphysiological experimental conditions (2), the use of an indirect method for assessment of cerebral blood flow (3), and the limited number of experiments performed (4). The present study was undertaken to obtain conclusive evidence on the upper limit of autoregulation. Normocapnic baboons were used, and cerebral blood flow was measured by the intracarotid 133 Xe injection method. The involvement of sympathetic nerves in the regulation of cerebral blood flow during acutely induced hypertension was also evaluated. MethodsThe study was carried out in ten young adult baboons {Papio cynocephalus or Papio anubis) weighing 10-14 kg. Three of the baboons were studied 2 weeks after a unilateral cervical sympathectomy, and one baboon was studied immediately after an acute cervical sympathetic block. The baboons were anesthetized with phencyclidine (12 mg, im) and sodium thiopental (7.5 mg/kg, iv). They were intubated and connected to ...

Hypertensive encephalopathy.

“…7 Howev er, recent studies have suggested that it may not be regions of vessel narrowing which are at fault but areas of abnormal vasodilation that represent a "break through" of autoregulation. 8 These latter observations suggest that there are regions of resistance vessels where smooth muscle contractility is overcome by in creased intraluminal pressure, leading to vascular damage and subsequent cerebral edema. CBF studies in patients with acute hypertension have documented areas of increased CBF and have been used to support the "breakthrough" hypothesis.…”

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

“…12,30,31 For obvious reasons, the upper limit of sCA cannot be studied in (normotensive) humans, but in normotensive baboons, it ranges between 120 and 150 mm Hg. 13 In humans with untreated severe chronic hypertension, the lower limit of sCA is shifted rightward to Ϸ115 mm Hg. 11,12 Data on the upper limit of sCA are limited in that it was determined in only 3 hypertensive baboons and was found to be shifted rightward (between 155 and 169 mm Hg).…”

“…11,12 For obvious reasons, the upper limit of CA has not been determined in normotensive or hypertensive humans. It was located between 120 and 150 mm Hg 13 in normotensive baboons and between 155 and 170 mm Hg in chronic hypertensive baboons. 14 A moderate reduction in BP with SNP in normotensive subjects does not influence CBF, 15 but to the best of our knowledge, no human studies specifically tested the assumption that CA is impaired in patients with malignant hypertension.…”

Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats.

“…These abnormalities include increased cerebral vascular permeability to dye and proteins, 1 ' 2 a loss or "breakthrough" of autoregulation, and forced dilation of the arterial vasculature, which imparts a "sausage-string" appearance. 3 - 4 Additionally, we and our colleagues have shown that following acute hypertension induced by pressor agents or experimental traumatic brain injury, abnormalities of the cerebral arterioles are caused by oxygen radicals formed during increased arachidonic acid metabolism. 5 - 7 The abnormalities include sustained dilation, decreased reactivity to hypocapnia, endothelial leFrom the Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Va.…”