Effects of verapamil on acute focal cerebral ischemia

Recent studies have suggested a role for disturbed calcium (Ca⁺⁺) metabolism in producing irreversible neuronal injury in ischemia. The objective of the present investigation was to study the effects of verapamil, a Ca⁺⁺ entry-blocking agent, on experimental focal cerebral ischemia in the cat. Twenty adult cats underwent right middle cerebral artery (MCA) occlusion for 6 hours. Ten cats were not treated. Ten cats received a continuous infusion of verapamil (0.2 mg/kg/hour) into the right carotid artery beginning 1 hour before MCA occlusion and continuing throughout the occlusion period. An additional bolus of verapamil (0.5 mg/kg) was injected into the right carotid artery immediately before MCA occlusion. The systemic arterial blood pressure and heart rate were similar in the two groups. Regional cerebral blood flow (rCBF) in the right sylvian region measured before and during MCA occlusion failed to show significant differences. Electroencephalographic changes were similar. Breakdown of the blood-brain barrier to Evans blue and fluorescein was not modified by treatment. The percentage of cross sectional gray matter area where severe neuronal alterations predominated was 44 ± 17% (SD) in the untreated group and 44 ± 20% in the verapamil-treated group (i.e., no significant difference). Microscopic changes, such as astrocytic swelling and capillary luminal narrowing, were consistently seen in areas where severe neuronal alterations predominated. The findings of the study indicated that verapamil did not improve rCBF and did not protect ischemic brain in acute focal cerebral ischemia.