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.
Ryan
Jonathon B
JB
Heart and Lung Transplant Unit, St Vincent's Hospital and the Victor Chang Cardiac Research Institute, Sydney, Australia
Hicks
Mark
M
Cropper
Jonathan R
JR
Nicholson
Anthony
A
Kesteven
Scott H
SH
Wilson
Michael K
MK
Feneley
Michael P
MP
Macdonald
Peter S
PS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D006321:Heart; D016027:Heart Transplantation / Q000502:physiology; D019188:Organ Preservation Solutions; D011281:Pregnatrienes / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014184:Transplantation, Homologous
D000975:Antioxidants; D002314:Cardioplegic Solutions; D019188:Organ Preservation Solutions; D011281:Pregnatrienes; C074965:U 74389F