LAZAROID (U74500A) PREVENTS VASCULAR AND MYOCARDIAL DYSFUNCTION AFTER24-HOUR HEART PRESERVATION - A STUDY BASED ON CROSS-CIRCULATED BLOOD-PERFUSED RABBIT HEARTS

Background The prevention of ventricular and vascular dysfunction has been recognized as an important factor in heart preservation. Because Lipid peroxidation map cause cell membrane injury after ischemia and r eperfusion, we hypothesized that the administration of a lipid peroxid ation inhibitor lazaroid (U74500A) would result in an improvement of f unctional recovery after the 24-hour preservation period. Methods and Results An isolated rabbit heart preparation perfused with support rab bit blood was used. Before preservation, 4 mg/kg of either lazaroid or solvent was given to donor rabbits. The hearts were preserved with Un iversity of Wisconsin solution for 24 hours at 0 degrees C. The workin g model preparation (n=7 in each group) showed a better cardiac output (74.6 +/- 25.7 versus 192.7 +/- 19.6 mL/min, P<.0001) and a lower lip id peroxide level (2.1 +/- 1.3 versus 0.6 +/- 0.3 nmol/mL, P<.05) of t he coronary effluent in the heart treated with lazaroid. With a Langen dorff preparation (n=7 in each group), we evaluated the vascular dilat ory function. The endothelial function assessed by the percentage incr ease of coronary how in response to acetylcholine in the solvent group was significantly lower than that of the lazaroid group 69 +/- 24% ve rsus 140 +/- 67%, P<.05), whereas no significant difference was observ ed between the groups regarding endothelium-independent vasodilatation as assessed by the responses to nitroglycerin and nitroprusside. Conc lusions These results demonstrated an improved ventricular and endothe lial function in the rabbit pretreated with lazaroid before preservati on accompanied by a reduction of lipid peroxidation, indicating the po tential benefits for long-term heart preservation.