Lazaroid (U74389G)-supplemented cardioplegia: Results of a double-blind, randomized, controlled trial in a porcine model of orthotopic heart transplantation

Background: U74389G (16-desmethyl tirilazad), a 21-aminosteroid or "lazaroid," inhibits lipid peroxidation, which is an important element of ischemia-reperfusion injury. The aim of this study was to determine whether the addition of U74389G to the cardioplegic preservation solution could improve early cardiac allograft function. Methods: A porcine model of donor brain death and orthotopic cardiac transplantation was used. Hearts were arrested and preserved for 6 hours in an aspartate-enriched extracellular cardioplegia that had been supplemented with either U74389G and its carrier (n = 7) or the carrier alone (n = 9). Epicardial sonomicrometry and transmyocardial micromanometry were used to obtain pressure-volume loops before and after transplantation. Left ventricular wall volume was measured by volume displacement. Results: A higher proportion of U74389G-treated hearts were weaned successfully from cardiopulmonary bypass, but this difference did not achieve statistical significance (86% [6 of 7] vs 56% [5 of 9]; p = 0.308). In the hearts that were weaned successfully, preservation of left ventricular contractility, as judged by the pre-load recruitable stroke work relationship, was significantly better in the U74389G-treated hearts (p = 0.0271). In contrast, left ventricular compliance, as judged by the end-diastolic pressure-volume relationship, was significantly better preserved in the control group (p < 0.0001). U74389G-treated hearts developed less myocardial edema, as judged by the post-transplant left ventricular wall volume/baseline steady-state epicardial end-diastolic volume ratio (64 ± 9% vs 76 ± 11%; p = 0.045). Conclusions: The benefit obtained from U74389G-supplemented cardioplegic preservation solution was marginal for hearts stored for 6 hours. After longer ischemic times, the benefit may be clearer.