ICAM-1 affects reperfusion injury and graft function after cardiac transplantation

Background. The effects of increased expression of intercellular adhesion m olecule (ICAM-1), an important mediator of neutrophil-mediated reperfusion injury (RI), were assessed in donor cardiac allografts in a heterotopic rat transplantation model. Methods. At -24 h, PVG donors were untreated (n = 35) or treated (n = 37) w ith lipopolysaccharide (LPS, 5 mg/kg ip). Hearts were procured at 0 h, stor ed at 4 degrees C for 45 min, and grafted heterotopically into ACI recipien ts pretreated with vehicle or anti-ICAM-1 (1A29) mAb. Intracardiac balloons (n = 8 per group) were used to measure allograft left ventricular function (dP/dt) prior to harvest and following reperfusion. RI was assessed at 6, 12, and 24 h by myeloperoxidase (MPO) levels, percentage wet weight (%w/w), and percentage contraction band necrosis (%CBN). Results. At 12 h, LPS-pretreated grafts showed increased ICAM-1 expression by Northern blot (n = 3) and immunohistochemistry (n = 3) and significantly increased MPO (0.33 +/- 0.2 U/mg vs 0.05 +/- 0.04 U/mg at 12 h), %w/w (81. 7 +/- 1.8% vs 79.2 +/- 0.7% at 12 h), and %CBN (15.2 +/- 1.9% vs 11.4 +/- 2 .0% at 24 h). LPS pretreatment had no effect on graft function at early tim e paints (baseline to 2 h) but led to depressed dP/dt at later time points with trends toward significance at 12 h (2101 +/- 1653 mmHg/s vs 173 +/- 20 1 mmHg/s, P = 0.06, ANOVA). Recipient 1A29 treatment (n = 6 per group) reve rsed the effects of LPS pretreatment in all three RI parameters and signifi cantly improved functional recovery. Conclusions. Alteration of cardiac graft phenotype to that likely seen in c linical organ donors leads to increased delayed-onset myocardial RI followi ng transplantation in this model. The blockade of this increased RI followi ng 1A29 mAb treatment supports a central role for ICAM-1 in this process. ( C)1999 Academic Press.