Contractile dysfunction in experimental cardiac allograft rejection: Role of the poly (ADP-ribose) polymerase pathway

Gábor Szabó, Susanne Bährle, Nicole Stumpf, Csaba Szabó, Siegfried Hagl

    Research output: Contribution to journalArticle

    6 Scopus citations

    Abstract

    Recent studies suggested that the peroxynitrite-poly (ADP-ribose) polymerase (PARP) pathway is activated during acute allograft rejection. We investigated whether PARP inhibition improves transplant function during cardiac rejection. Isogeneic Lewis-to-Lewis and allogeneic Dark Agouti-to-Lewis rat cardiac transplants were studied under treatment with placebo or with the PARP-inhibitor INO-1001 (1 mk/kg/day), Functional, biochemical and histological analysis were performed 3 and 5 days after transplantation. After 3 days, baseline left ventricular pressure-volume relationships did not differ between the groups. However, coronary blood flow (4.3 ± 0.5 vs. 2.2 ± 0.2 vs. 4.1 ± 0.3 ml/min/g, P < 0.05) and contractile response to dobutamine (Δ+dP/dt: 98 ± 11 vs. 57 ± 7 vs. 88 ± 8%, P < 0.05) decreased significantly in the placebo group, which was abolished by INO-1001. Vasodilatory response to acethylcholine was reduced in the placebo group (78 ± 6 vs. 36 ± 9 vs. 72 ± 7%, P < 0.05). After 5 days, baseline systolic and diastolic pressure-volume relationships were impaired (P < 0.05) in the placebo group and the response to dobutamine and to acethylcholine deteriorated further which was abolished by INO-1001. Histology confirmed mild to moderate rejection after 3 days and severe acute rejection after 5 days in the allogeneic groups. Thus, contractile and vasomotor dysfunction occur in a typical time dependent manner during cardiac rejection, which can be reduced by PARP-inhibition.

    Original languageEnglish (US)
    Pages (from-to)506-513
    Number of pages8
    JournalTransplant International
    Volume19
    Issue number6
    DOIs
    StatePublished - Jun 2006

    Keywords

    • Cardiac function
    • PARP
    • Rat
    • Rejection
    • Transplantation

    ASJC Scopus subject areas

    • Transplantation

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