• Eur J Cardiothorac Surg · Feb 2005

    Poly(ADP-ribose) polymerase inhibition attenuates biventricular reperfusion injury after orthotopic heart transplantation.

    • Gábor Szabó, Pál Soós, Ulrike Heger, Christa Flechtenmacher, Susanne Bährle, Zsuzsanna Zsengellér, Csaba Szabó, and Siegfried Hagl.
    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. dzsi@hotmail.com
    • Eur J Cardiothorac Surg. 2005 Feb 1; 27 (2): 226-34.

    ObjectivePoly (ADP-ribose) polymerase (PARP) activation plays a key role in free radical induced injury in ischemia/reperfusion. We investigated the effects of INO-1001 a novel PARP inhibitor on postischemic myocardial and endothelial function.MethodsIn dogs, 12 orthotopic heart transplantations were performed after 4 h ischemic preservation. At the beginning of reperfusion either saline vehicle (control, n=6), or INO-1001 (1 mg/kg, n=6) was applied. Before explantation and after 120 min of reperfusion we measured biventricular pressure-volume relationships by a combined conductance catheter and the adaptation potential of the right ventricle to acute afterload increase by pulmonary banding. Coronary blood flow (CBF), vasoreactivity, PARP-activation and ATP-content were also determined.ResultsINO-1001 led to significantly better recovery of contractility (91+/-3 vs. 44+/-7%, P<0.05) and CBF (44+/-4 vs. 29+/-3 ml/min, P<0.05) and higher increase in CBF after acetylcholine (61+/-10 vs. 27+/-8%, P<0.05). In addition, the inotropic adaptation potential of the right ventricle to an increased afterload was better preserved after INO-1001. ATP content was significantly higher in the INO-1001 group (11.0+/-2.1 vs. 4.5+/-1.1 micromol/g drw). Immunohistology revealed PARP activation in the control group which was abolished by INO-1001 treatment.ConclusionsPARP inhibition reduces myocardial and endothelial reperfusion injury after orthotopic heart transplantation.

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