Molecular mechanism of contractile dysfunction in cardiac allograft rejection

Abigail K. Hanna, Michael Louie, Jean Miller, Alec Hirsch, Bruce T. Liang, Verdi J. DiSesa

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Alterations in the β-adrenergic receptor adenylyl cyclase pathway are well known in heart failure. To determine if an alteration in this pathway occurs during the reversible phase of cardiac allograft rejection, we used a rat heterotopic heart transplant model. Lewis rats received either isografts or Lewis Brown Norway allografts. Cardiac grafts and native hearts were explanted 4, 5, or 6 days later. Receptor-mediated modulation of adenylyl cyclase activity was investigated using isoproterenol, forskolin, and the muscarinic and adenosine receptor agonists carbachol and R-N6-(C2-phenyl-isopropyl)-adenosine (R-PIA), respectively. Allografts demonstrated evidence of histological rejection and a significantly impaired response to forskolin and isoproterenol on all days: {A table is presented} (% increase in cAMP in response to forskolin or isoproterenol ± standard error. All results P < 0.03 except Day 4 forskolin and Day 5 isoproterenol.) No significant difference was noted between isografts and allografts stimulated with carbachol and R-PIA. These data suggest that a primary alteration in adenylyl cyclase activity may be a component of the molecular basis of reversible contractile dysfunction in cardiac allograft rejection.

Original languageEnglish (US)
Pages (from-to)472-475
Number of pages4
JournalJournal of Surgical Research
Issue number5
StatePublished - May 1992
Externally publishedYes

ASJC Scopus subject areas

  • Surgery


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