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

Robert S. Poston, Doug J. Ing, Michael P. Ennen, E. Grant Hoyt, Robert C. Robbins

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background. The effects of increased expression of intercellular adhesion molecule (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) with lipopolysaccharide (LPS, 5 mg/kg ip). Hearts were procured at 0 h, stored at 4°C for 45 min, and grafted heterotopically into ACI recipients 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 time points (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 ± 201 mmHg/s, P = 0.06, ANOVA). Recipient 1A29 treatment (n = 6 per group) reversed the effects of LPS pretreatment in all three RI parameters and significantly improved functional recovery. Conclusions. Alteration of cardiac graft phenotype to that likely seen in clinical organ donors leads to increased delayed-onset myocardial RI following transplantation in this model. The blockade of this increased RI following 1A29 mAb treatment supports a central role for ICAM-1 in this process.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalJournal of Surgical Research
Issue number1
StatePublished - Nov 1999
Externally publishedYes


  • Antibodies
  • Ischemia
  • Receptors
  • Reperfusion
  • Transplantation

ASJC Scopus subject areas

  • Surgery


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