Cerebral oxygen availability and blood flow during middle cerebral artery occlusion: effects of pentobarbital.

Abstract

SUMMARY To determine whether barbiturate administration can improve oxygenatlon, oxygen availability (aOi) and local cortical blood flow (1CBF) were measured in cats before and during middle cerebral artery occlusion (MCAO) using 10 platinum electrodes distributed over the cortex. Halothane/N,O anesthesia was used during the surgical preparation and N,0 with a relaxant thereafter. After 15 to 30 rain of MCAO, 50 rag/kg of pentobarbital was infused slowly. Measured from electrodes in severely ischemic cortex, aO, increased if the blood pressure was maintained with dopamine. Control animals in which no pentobarbital was given showed no change in aO, over the same period of time. In areas of cortex not affected by middle cerebral artery occlusion the aO, did not change from control values despite a decrease in blood flow from 72.7 ± 49.8 to 48.9 ± 26.7 ml/min/100 g. Thus, pentobarbital appears to decrease ICBF and metabolism proportionally in well perfused cortex so that aOi remains constant, while improving the flow to metabolism ratio in poorly perfused cortex so that aO, rises.Stroke, Vol 12, No 6, 1981BARBITURATES have been shown to reduce infarct size following middle cerebral artery occlusion in some species of animals.1 " 4 The mechanism of protection is unknown. This study was designed to determine the relative O, tension and blood flow responses of normal and ischemic cat cerebral cortex to large doses of barbiturates. Changes in cortical O, may help explain how barbiturate treatment results in smaller infarct sizes following middle cerebral artery occlusion (MCAO).Branston et al. 8 have reported that barbiturates increased flow in micro-areas of baboon cortex where flow during MCAO was less than 20 ml/min/100 g. Their results are consistent with an inverse steal hypothesis for barbiturates. This hypothesis states that vasoconstriction of non-ischemic cortex results in an elevated microvascular pressure which can then lead to increased flow through anastomotic channels to ischemic tissue. A second hypothesis is that barbiturate protection is secondary to the resulting decreased metabolic rate and oxygen requirement. However, all agents which decrease metabolic rate do not have a protective effect.*-e The important variable for tissue oxygenation is the ratio of flow to metabolism. This determines the amount of oxygen available for metabolism and also the gradient for diffusion to the mitochondria. Thus, increases in flow combined with decreases in metabolism may amount to a more substantial improvement in tissue oxygenation than flow measurements alone would indicate. Therefore, it is desirable that either flow and metabolism both be measured at the same location or that a single parameter, which reflects the flow to metabolism ratio, be measured. Clark et al. 7 have defined oxygen availability (aO,) as the amount of oxygen reduced at a platinum cathode in tissue. It is an estimate of the oxygen delivery minus the locally metabolized oxygen. Therefore, aO, was measured in micro-areas of cat cortex before m...

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“…Barbiturates were shown to reduce the cerebral metabolic rate by 50 to 60% and to increase cerebral blood flow to areas of ischemic cortex. [4][5][6][7] The unique properties of etomidate, which produce marked depression of cerebral metabolism with minimal cardiac toxicity, prompted the autors to try this agent for maintening cerebral circulation during temporary arterial occlusion in the treatment of aneurysms. 3,8,9,10 Mannitol administration was demonstrated to enhance cerebral blood flow by reducing blood viscosity; the use of mannitol alone or in combination with other agents was suggested prior to temporary vascular occlusion.…”