The effect of alkalizing agents on experimental focal cerebral ischemia.

We investigated the immediate effect of tris (hydroxymethyl) aminomethane (THAM) and NaHCO3 on focal cerebral ischemia produced by occlusion of the left 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 groups received continuous administration of 0.3 mol THAM and 7% NaHCO3, respectively, to normalize arterial pH. Local CBF measured in the marginal and suprasylvian gyri decreased less than 30 ml/100 g/min after the MCA occlusion and there were no significant differences among the three groups. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.21 to 6.86 in the control group. However, extracellular pH did not show significant changes in the THAM and NaHCO3 groups. Intracellular pH of the infarct area decreased from 7.23 to 6.13 in the control group within 6 hours after occlusion. THAM had a tendency to normalize intracellular pH compared with that in the control and NaHCO3 groups. THAM significantly (p < 0.05) decreased water content of the gray matter in the marginal gyrus at 6 hours after occlusion and the infarct size compared with those in the control and NaHCO3 groups. Therefore, normalization of systemic and perifocal acidosis with THAM is effective for reducing cortical edema and infarct size in the early stage of focal cerebral ischemia probably due to the improvement of intracellular acidosis.