Cardioprotective effects of amlodipine in animal models of ischemia and reperfusion.

The protective effect of amlodipine was studied in isolated blood-perfused cat hearts made globally ischemic for 60 min followed by reperfusion for 60 min. Ischemia-induced alterations of left ventricular developed pressure and compliance were monitored. Amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml of oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). When administered before the onset of global ischemia, amlodipine decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 min after reperfusion, was improved significantly in amlodipine-treated hearts compared to controls and there was better maintenance of the tissue concentration of Na+, Ca2+, and K+. In a canine model of regional myocardial ischemia (6 h) followed by reperfusion, amlodipine at 150 microg/kg, administered 15 min before reperfusion (90 min), reduced infarct size expressed as a percentage of the area at risk (34.5 +/- 3.8% vs. 45.9 +/- 2.8%, p = 0.027). We conclude 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.