BENEFICIAL-EFFECTS OF FELODIPINE ON MYOCARDIAL AND CORONARY FUNCTION DURING LOW-FLOW ISCHEMIA AND REPERFUSION

An acute coronary occlusion causes severe low-flow ischemia in the occ luded region. Calcium antagonists have the potential to reduce the rat e of ischemic injury by decreasing myocardial oxygen demand, as well a s by other mechanisms, especially when given prior to the onset of isc hemia. However, their clinical use may be limited by their negative in otropic effects. The purpose of this study was to assess the effects o f felodipine as a potentially protective agent against myocardial isch emia and reperfusion injury, independent of any negative inotropic act ions, when given after the onset of low-flow ischemia. Isolated isovol umic (balloon-in-LV), blood-perfused rabbit hearts, paced at a constan t heart rate, were subjected to 90 minutes of low-flow ischemia at a c oronary perfusion pressure of 10 mmHg, which reduced coronary blood fl ow to 22-24% of baseline. After 15 minutes of low-flow ischemia, heart s received 2 x 10(-6) M felodipine (n = 7) or no drug (controls, n = 8 ). Felodipine was given until 15 minutes of reperfusion. During low-fl ow ischemia both groups of hearts had identical coronary blood how, he art rate, left ventricular (LV) developed pressure, lactate production , and O-2 consumption. However, felodipine markedly protected against ischemic diastolic dysfunction. At the end of low-how ischemia, LV end -diastolic pressure (LVEDP) had increased from 10 +/- 1 to 28 +/- 5 mm Hg in the felodipine group, while in the controls LVEDP increased to 4 8 +/- 8 mmHg (p < 0.05). During 30 minutes of reperfusion, felodipine had a beneficial effect upon coronary blood how (initial postischemic hyperemia 245 +/- 38% of baseline in the felodipine group vs. 124 +/- 18% in the controls; p < 0.01) Felodipine markedly improved the recove ry of contractile function [LV developed pressure recovered from a bas eline of 104 +/- 4 to 75 +/- 6 mmHg (72%) in the felodipine group vs. 34 +/- 10 mmHg (32%) in the control group; p < 0.01], as well as diast olic function (LVEDP = 25 +/- 4 mmHg in the felodipine group vs. 61 +/ - 10 mmHg in the controls; p < 0.05), and ATP levels (8.5 +/- 1.4 mu m oles/g d.w. in the felodipine group vs. 3.9 +/- 1.4 mu moles/g d.w. in the control group, p < 0.05). Felodipine, given after the onset of lo w-flow ischemia, protects the myocardium during both ischemia and repe rfusion by mechanisms other than reducing myocardial oxygen demand.