Lazaroid (U74500A) prevents vascular and myocardial dysfunction after 24-hour heart preservation. A study based on cross-circulated blood-perfused rabbit hearts.

Abstract

The prevention of ventricular and vascular dysfunction has been recognized as an important factor in heart preservation. Because lipid peroxidation may cause cell membrane injury after ischemia and reperfusion, we hypothesized that the administration of a lipid peroxidation inhibitor lazaroid (U74500A) would result in an improvement of functional recovery after the 24-hour preservation period. An isolated rabbit heart preparation perfused with support rabbit blood was used. Before preservation, 4 mg/kg of either lazaroid or solvent was given to donor rabbits. The hearts were preserved with University of Wisconsin solution for 24 hours at 0 degree C. The working 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 lipid peroxide level (2.1 +/- 1.3 versus 0.6 +/- 0.3 nmol/mL. P < .05) of the coronary effluent in the heart treated with lazaroid. With a Langendorff preparation (n = 7 in each group), we evaluated the vascular dilatory function. The endothelial function assessed by the percentage increase of coronary flow in response to acetylcholine in the solvent group was significantly lower than that of the lazaroid group (69 +/- 24% versus 140 +/- 67%, P < .05), whereas no significant difference was observed between the groups regarding endothelium-independent vasodilatation as assessed by the responses to nitroglycerin and nitroprusside. These results demonstrated an improved ventricular and endothelial function in the rabbit pretreated with lazaroid before preservation accompanied by a reduction of lipid peroxidation, indicating the potential benefits for long-term heart preservation.