Comparative Anti-Ischemic Effects of Dihydropyridine Calcium Antagonists in Isolated Perfused Rat Hearts: Relationship of Cardiodepression and Cardioprotection

Abstract

A comparison was made of the anti-ischemic effects of dihydropyridine calcium antagonists in isolated globally ischemic rat hearts. Pretreatment with amlodipine, nifedipine, nitrendipine, or nisoldipine reduced reperfusion enzyme (lactate dehydrogenase) release and contracture after 25 min of global ischemia and 30 min of reperfusion. Increasing concentrations of all compounds resulted in proportionally smaller reductions in the severity of ischemia, with larger decreases in nonischemic tissue contractility occurring. Reperfusion function was significantly improved at 30 min with nifedipine only; however, at 60 min reperfusion function was significantly improved for all except nisoldipine. Washout data from nonischemic hearts (rate of disappearance of cardiodepressant effects) showed that the dihydropyridines washed out in the following order (fastest to slowest): nifedipine > nitrendipine > nisoldipine > amlodipine. Thus, these dihydropyridines are anti-ischemic, though at higher concentrations cardiodepressant effects increase disproportionately. Differences in washout also effect the ability of these compounds to improve reperfusion function.

Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart

“…In this study, we used an in vitro Langendorff-perfused heart preparation to study the mechanical and tissue injury aspects of ischemia-reperfusion. Among the advantages of this commonly employed model (1,2,7,8,16,17,20,33) is that key elements of cardioprotection (i.e., infarct sparing and preserved mechanical function) can be studied in the absence of cardiac innervation, blood-borne inflammatory cell types, or other factors extrinsic to the myocardium that may influence the response of the heart to ischemia. These advantages are gained at the expense of the physiological context that is eliminated.…”