Nimodipine‐induced changes in the distribution of carotid blood flow and cardiac output in pentobarbitone‐anaesthetized pigs

Abstract

In view of the claimed effectiveness of nimodipine in migraine and its possible selectivity for cerebral vessels, we investigated the effects of nimodipine in anaesthetized pigs on the fractionation of carotid arterial blood flow into non‐nutrient (arteriovenous anastomoses; AVAs) and nutrient (capillary) parts, and on regional tissue blood flows and vascular conductances. Intracarotid infusions of nimodipine (0.05‐1.25 μg kg−1 min−1) redistributed carotid blood flow in favour of its nutrient compartment, particularly to the skeletal muscles and tongue. Vascular conductance in the non‐nutrient (AVAs) compartment decreased (40%), most likely, as a result of ‘steal’ following profound (5.5 fold) arteriolar dilatation. Intravenous infusions of nimodipine (0.05–6.25 μg kg−1 min−1) caused hypotension, bradycardia, a decrease in conduction in the non‐nutrient fraction, and an increase in conduction in the nutrient fraction (mostly in the skeletal muscles, but also in the gastrointestinal tract, cerebral hemispheres, heart and adrenals). Probably due to the hypotensive effect, only skeletal muscle blood flow increased. The nimodipine‐induced increase in vascular conductance in the skeletal muscles showed regional variation; the effect was most pronounced in the cheek muscles, followed by the muscles of the chest, abdominal, trunk and gluteal regions. We conclude that: (i) AVA flow seems to represent a ‘reserve’ perfusion which can be readily diverted to tissues in the case of increased metabolism and/or vasodilatation, (ii) though the overall response to nimodipine of carotid blood flow distribution qualitatively resembles that to some anti‐ migraine drugs, the relevance of such acute effects in the prophylactic usefulness of nimodipine in migraine remains to be ascertained, and (iii) nimodipine lacks a selective cerebral vasodilator action in the anaesthetized pig. 1986 British Pharmacological Society