CEREBRAL VASODILATION AND SPASMOLYTIC ACTIVITY OF DILTIAZEM IN ANESTHETIZED ANIMALS

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The effects of diltiazem on the cerebral blood flow and cerebrovascular spasm were studied in pentobarbital anesthetized animals. In Rhesus monkeys, the common carotid and internal carotid blood flow were measured by an electromagnetic flowmeter. Diltiazem (10-300 μg/ kg, i.v.) dose-dependently increased both the common carotid and internal carotid blood flow, and the increase in internal carotid blood flow persisted for a longer period than that in the common carotid blood flow. In dogs, regional blood flow in the cerebral cortex (rCBF) was measured by means of the hydrogen gas clearance method. Diltiazem (20 μg/kg/min, i.v.) increased rCBF by about 20% of the control during the infusion, and the increase in rCBF was still continued 40 min after the infusion was stopped. In cats, the basilar artery was exposed by craniotomy through the transcervico-transclival approach, and vasospasm was induced by topical administration of 5-HT, PGF<SUB>2α</SUB> and incubated blood. Diltiazem, either applied topically to the artery (100 μg/ml) or infused continuously into the femoral vein (20 or 40 μg/kg/min), suppressed the vasoconstriction evoked by the spasmogen.
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