Abstract
Metabolic acidosis in cerebral ischemia is considered deleterious to cell function. Amelioration of systemic and focal cerebral acidosis by an alkalizing agent may reduce ischemic brain damage. We examined the effect of tris [hydroxymethyl] aminomethane (THAM) and NaHCO3 on focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in cats. The animals were divided into three groups. In the control group, physiological saline was infused continuously. The THAM and NaHCO3 group received continuous administration of 0.3 mol THAM and 7% NaHCO3, respectively. PaO2, PaCO2 and the mean arterial blood pressure in each group were maintained within the normal range. The following experimental results were obtained. In the THAM and NaHCO3 groups, the arterial pH was maintained within the normal range, whereas in the control group, it gradually fell from 7.39 at the start to 7.28 at 6 hours after the MCA occlusion. The local CBF measured by the hydrogen clearnace method in the marginal and suprasylvian gyri promptly decreased after the MCA occlusion and there were no significant differences among the three groups. The extracellular pH measured with a glass electrode on the marginal gyrus declined from 7.36 to 6.87 after 6 hours of ischemia in the control group. However, in the THAM and NaHCO3groups, the extracellular pH failed to show significant changes during the 6 hours of occlusion. In the THAM group, the water content of the gray metter measured by the specific gravimetric method in the marginal gyrus was significantly decreased compared to that in the control and NaHCO3 groups. The tissue lactate content measured by an enzymatic assay in the marginal gyrus fell singificantly following the administration of THAM, but was significantly increased in the NaHCO3 group, as compared to the control group. These data suggest that alkalizing agents tend to improve the extracellular pH, but exert less effect on the cerebral circulation. We consider that the normalization of systemic and perifocal acidosis elicited by THAM is effective for reducing cortical edema at the early stage of focal cerebral ischemia. This effect of THAM is probably due to improvement of the cellular metabolism. NaHCO3also normalized systemic and extracellular acidosis, but it exerted no effect on cerebral edema. The above results suggest therefore that NaHCO3 infusion may lead to paradoxical intracellular acidosis, and that THAM is more effective than NaHCO3 at the early stage of cerebral ischemia.
