Altered coronary flow responses to vasoactive drugs in the presence of coronary arterial stenosis in the dog

Abstract

Recent in vitro observations of human coronary arteries have suggested that intraluminal pressure can be a determinant of the resistance to flow through the stenosis. This study examined whether similar pressure-dependent changes in stenotic resistance could be observed and analyzed in an open chest, anesthetized, animal model of coronary arterial stenosis. Without stenosis, intracoronary isoproterenol (1 μg) or nitroglycerin (10 μg) increased flow and decreased coronary resistance, whereas methoxamine (500 μg) or vasopressin (0.2 U) decreased flow and increased coronary resistance. After partial arterial constriction, administration of isoproterenol (1 μg) resulted in a decrease in coronary pressure from 61.2 ± 2.5 to 39.4 ± 2.7 mm Hg (p ≤ 0.05), a 23 percent derease in distal coronary resistance (p ≤ 0.05) and a 22 percent decrease in flow associated with an increase in stenotic resistance of 2.34 ± 0.97 (p ≤ 0.05). Similarly, nitroglycerin caused a decrease in coronary pressure from 55.7 ± 3.1 to 42.1 ± 3.6 mm Hg (p ≤ 0.05), a 29 percent increase in distal coronary resistance and only a 1 percent increase in flow associated with a 38 percent increase in stenotic resistance. Methoxamine caused an increase in coronary pressure from 62.8 ± 2.0 to 73.6 ± 3.4 mm Hg (p ≤ 0.05), an 18 percent increase in distal coronary resistance, an 8 percent decrease in flow and a 10 percent decrease in stenotic resistance. Vasopressin caused an increase in coronary pressure from 61.0 ± 1.5 to 99.2 ± 7.1 mm Hg (p ≤ 0.05), a 239 percent increase in distal coronary resistance but only a 45 percent decrease in flow associated with a decrease in stenotic resistance of 1.33 ± 0.91 (p ≤ 0.05). Passive changes in the stenotic area caused by coronary pressure changes are postulated as part of the mechanism for the observed changes in stenotic resistance. This hypothesis is strengthened by the changes in stenotic resistance and radiographic analysis obtained from an in vitro carotid arterial preparation. The pressure-dependency of stenotic resistance could be an additional factor in the treatment of patients with coronary artery disease.