Selective improvement in subendocardial perfusion distal to a flow-limiting coronary artery stenosis: effects of the new calcium channel blocking agent, FR 34235, nifedipine and diltiazem.

The purpose of the present study was to compare the effects of a new calcium channel blocker, FR 34235, on the distribution of blood flow between subendocardium and subepicardium (endo/epi) distal to a proximal flow-limiting coronary artery stenosis, with those of nifedipine and diltiazem in anesthetized dogs. Myocardial blood flow distribution was determined by using 15-mu radioactive microspheres. Various indices of reactive hyperemia (peak flow, duration and reactive hyperemia volume), poststenotic coronary pressures and myocardial contractility (Walton-Brodie strain gauge) were used to assess the severity of ischemia in the area distal to the stenosis. Partial ischemia was produced by a 10-sec total left circumflex coronary occlusion followed by 110 sec of reflow to approximately 50 to 60% of the control flow. Microspheres were injected during the partial reflow period. During control coronary stenosis the subendocardium was markedly underperfused (endo/epi = 0.53 +/- 0.08) and myocardial contractility depressed. Following FR 34235 (1 microgram/kg i.v.), nifedipine (2 micrograms/kg i.v.) or diltiazem (30 micrograms/kg i.v.), the endo/epi and myocardial contractility during partial reflow were significantly increased. In addition, reactive hyperemia duration and reactive hyperemic flow were reduced by all three compounds following release of the partial occlusion. These results suggest that FR 34235, nifedipine and diltiazem reduce subendocardial ischemia and improve myocardial function distal to a flow-limiting coronary artery stenosis. These beneficial actions may partially explain the efficacy of calcium channel blockers in the treatment of myocardial ischemia.