Cardiovascular actions of the calmodulin inhibitor felodipine

1432-1912

Vasodilation ; Coronary blood flow ; Myocardial O2-consumption ; Regional myocardial wall function ; Dihydropyridine derivative ; Pig

Springer Online Journal Archives 1860-2000

Medicine

Summary The cardiovascular effects of intravenous (1.5–10 nmol · kg−1) and intracoronary (50 nmol) administration of felodipine, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonylpyridine, were studied in anaesthetized pigs. Following intravenous administration dose-dependent decreases were observed in left ventricular systolic blood pressure (up to 30%) and in the resistances of the systemic (up to 40%) and coronary vascular beds (up to 45%), whereas heart rate, cardiac output, myocardial contractility (regional and global), and left ventricular end-diastolic pressure were minimally affected. Myocardial blood flow increased independently of the dose (20%), while the coronary venous O2-content more than doubled. The concomitant decrease in myocardial O2-consumption (up to 30%) was dose-dependent in the range from 1.5–6.75 nmol·kg−1. Intracoronary administration of 50 nmol had only minor effects on global and regional myocardial performance but produced a doubling of the coronary blood flow which was accompanied by a 70% decrease in myocardial O2-extraction. O2-consumption decreased considerably more (35%) than after intravenous administration in spite of the minimal decrease in O2-demand (7%). We conclude that felodipine dilates both systemic and coronary blood vessels. Although the reduction in myocardial O2-consumption is primarily caused by the reduction in afterload, a direct effect on myocardial metabolism can also be involved.

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