MYOCARDIOPROTECTIVE EFFECTS OF FELODIPINE IN AN ANTIHYPERTENSIVE DOSAGE - AN EXPERIMENTAL-STUDY IN PIGS

The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of Ischemia followed b y reperfusion. Comparing the cardioprotective effects of felodipine an d an agent of another class allowed the influence of blood pressure re duction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusio n. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes b efore the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) servin g as controls received a mixture of polyethylene glycol (PEG) and 5% g lucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion lev els, respectively. Infarct size as a percentage of the area at risk wa s 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the ve hicle groups, respectively. Felodipine, given in a dose resulting in p lasma levels corresponding to the therapeutic range in patients on ant ihypertensive treatment, reduced infarct size following myocardial isc hemia/reperfusion. Afterload reduction induced by nitroprusside did no t influence infarct size. Thus, felodipine exerted a myocardioprotecti ve effect unrelated to the mechanism of afterload reduction in clinica lly relevant antihypertensive dosages.