Mesenteric injury after cardiopulmonary bypass: Role of poly(adenosine 5′-diphosphate-ribose) polymerase

Gábor Szabó, Pál Soós, Susanne Mandera, Ulrike Heger, Christa Flechtenmacher, Leila Seres, Zsuzsanna Zsengellér, Falk Udo Sack, Csaba Szabó, Siegfried Hagl

    Research output: Contribution to journalArticlepeer-review

    9 Scopus citations

    Abstract

    Objectives: To investigate the effects of the ultrapotent poly(adenosine 5′-diphosphate-ribose) polymerase (PARP) inhibitor INO-1001 on cardiac and mesenteric function during reperfusion in an experimental model of cardiopulmonary bypass with cardioplegic arrest. Design: Prospective, randomized, and blinded experimental study. Setting: Research laboratory. Subjects: Twelve anesthetized dogs underwent cardiopulmonary bypass with hypothermic cardioplegic cardiac arrest. Interventions: After 60 mins of hypothermic cardiac arrest, either PARP inhibitor INO-1001 (1 mg/kg, n = 6) or vehicle (control, n = 6) was administered during reperfusion. Measurements and Main Results: Left ventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and mesenteric blood flow and vasodilatory responses to acetylcholine and sodium nitroprusside as well as mesenteric lactate and creatinine phosphokinase release were also determined. The administration of INO-1001 led to a significantly improved recovery of left ventricular systolic function (p < .05) after 60 mins of reperfusion. Coronary and mesenteric blood flow were also significantly higher in the INO-1001 group (p < .05). Although the vasodilatory response to sodium nitroprusside was similar in both groups before and after cardiopulmonary bypass and similar in response to acetylcholine before cardiopulmonary bypass, PARP-inhibited dogs had lower mesenteric vascular resistance after cardiopulmonary bypass (p < .05). Mesenteric lactate and creatinine phosphokinase release was significantly lower in the PARP inhibitor treated group (p < .05). Conclusion: PARP inhibition with INO-1001 improves the recovery of myocardial function and prevents mesenteric vascular dysfunction and tissue injury after cardiopulmonary bypass with hypothermic cardiac arrest.

    Original languageEnglish (US)
    Pages (from-to)2392-2397
    Number of pages6
    JournalCritical care medicine
    Volume32
    Issue number12
    DOIs
    StatePublished - Dec 2004

    Keywords

    • Cardioplegia
    • Cardiopulmonary bypass
    • Heart surgery
    • Mesenteric injury
    • Poly(adenosine 5′-diphosphate-ribose) polymerase
    • Reperfusion injury

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine

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