Cardioprotective effects of amlodipine in the ischemic-repefused heart

Abstract

Amlodipine is a a dihydropyridine derivative belonging to the group of pharmacologic calcium entry blocking agents and is characterized as having a slow onset and relatively long duration of action with minimal effects on cardiac electrophysiology and myocardial contractility.The protective effect of amlodipine was studied in isolated blood-perfused feline hearts made globally ischemic for 60 minutes followed by reperfusion for 60 minutes. Ischemic-lnduced alterations of left ventricular developed pressure and compliance were monitored. In 11 control and 7 drug-treated hearts, amloipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). Amlodipine administered before the onset of global ischemia decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 minutes after reperfusion, improved significantly in the amlodipine-treated group compared with controls, and there was better maintenance of the tissue concentration of Na+, Ca2+ and K+.A canine model of regional myocardial ischemia (90 minutes) followed by 6 hours of reperfusion was used to assess the cardioprotective effects of amlodyrine, 150 [mu]g/kg, administered 15 minutes before reperfusion. Infarct size, expressed as a percentage of the area at risk, was smaller in the amlodipine-treated group (n = 10) than in the control group (n = 10) (34.5 +/- 3.8% vs 45.9 +/- 2.8%, P = 0.027). Risk region size did not differ between groups and both groups were comparable with respect to the hemodynamic parameters of heart rate, blood pressure and rate-pressure product. Amlodipine prevented the gradual reduction in coronary blood flow observed in the control group.It is concluded that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.