Effects of cloricromene on ischemia-reperfusion myocardial damage in the rabbit

Cloricromene, a compound with several biological activities which suggest a therapeutic role in thrombosis or ischemic disease, has been studied for its effects on the extension of myocardial damage and the production of oxygen free radicals during periods of ischemia and reperfusion. In twenty rabbits the left anterior descending coronary artery (LAD) was occluded and cloricromene (3.6 micrograms/kg/min; n = 10) or placebo (n = 10) were continuously infused. After 50 min the artery was reopened and after 20 min of reperfusion a biopsy was obtained from the anterior wall of the heart in the LAD area and from the posterior wall (control myocardium) prior to sacrifice. Both samples were used for chemiluminescence measurement (free-radical production) and ultrastructural studies. In the placebo group all rabbits showed ST-segment changes during ischemia and reperfusion arrhythmias, while in the cloricromene group there were transient ST elevations in 4 animals which reverted at higher infusion rates of the drug. The chemiluminescence values were 18,017 +/- 1,956 and 8,583 +/- 918 cpm/mg protein (p < 0.001) in the anterior and posterior walls of the left ventricle, respectively, for the placebo group, and 7,767 +/- 992 and 8,333 +/- 832 cpm/mg protein (NS), respectively, for the cloricromene group. The ratio between the anterior and posterior wall was 2.27 +/- 0.37 for the placebo group versus 0.95 +/- 0.11 for the cloricromene group (p < 0.001). In ultrastructural studies, the anterior wall in the placebo group showed irreversible myocyte injury and infarction as well as mitochondrial damage. Samples from the cloricromene-treated group showed, in general, preservation of myocyte architecture or minor signs of injury. These results illustrate clearly the protective effect of cloricromene during damage induced by ischemia and reperfusion in the rabbit.