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 ...

SYNOPSISThe effect of graded, progressive hypotensioni on the autoregulation of cerebral blood flow was studied in anaesthetised baboons. Progressive hypotension was produced over a period of four to five hours, either by graded haemorrhage or by the administration of increasing concentrations of hypotensive drugs. During haemorrhagic hypotension autoregulation was maintained until the mean arterial pressure had decreased to 65% of its baseline value, below which cerebral blood flow was pressure passive. In those animals subjected to drug-induced hypotension, autoregulation persisted to lower levels of mean arterial pressure (35-40% of baseline). It is postulated that under conditions of haemorrhagic hypotension, constriction of the extraparenchymal cerebral vessels in response to sympathetic stimulation decreases the possible range ofautoregulation in the anaesthetised baboon.Since its introduction into anaesthetic and surgical practice (Gardner, 1946), controlled hypotension has been used extensively to reduce bleeding and to facilitate surgery. However, despite the widespread use of the technique, the indications for induced hypotension have not been defined clearly and considerable disagreement exists regarding its safety (Davison, 1958;Enderby, 1958; Mayrhofer, 1971). The primary objections stem from uncertainties regarding the adequacy of cerebral tissue perfusion during the period of lowered arterial pressure (Brierley and Cooper, 1962;Adams et al., 1966).The present investigations were undertaken to measure the effect of a graded and progressive decrease in systemic arterial pressure on the cerebral blood flow of anaesthetised baboons and to compare the effects of haemorrhagic and pharmacologically-induced hypotension. METHODSYoung adult baboons (9-14 kg) were tranquillised with phencyclidine (12 mg intramuscularly) and then anaesthetised with thiopentone (7.5 mg/kg intravenously), nitrous oxide and oxygen (70%:30%). In addition, half-hourly doses of phencyclidine (2 mg intramuscularly) and suxamethonium (100 mg intiamuscularly) were administered to prevent awareness and to produce muscular relaxation. The trachea was intubated and ventilation was controlled throughout each investigation (Starling respiratory pump), the minute volume and the inspired oxygen concentration being adjusted to produce normocapnia and normoxia. The end-tidal carbon dioxide concentration was monitored continuously by an infra-red analyser (URAS 4: Hartmann and Braun). During each determination of cerebral blood flow, the arterial pH and blood-gas tensions were measured using appropriate, suitably calibrated electrodes (Radiometer). Body temperature was maintained within normal limits (36°C-38°C) by means of heating lamps. Correction was made, where necessary, for any temperature difference existing between the animal and the electrode system (Severinghaus, 1966).Cerebral blood flow was determined by external scintillation counting over the right parietal area after 014 Protected by copyright. on 11 May 2018 by guest.