Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass

Gábor Szabó, Pál Soós, Susanne Bährle, Zsuzsanna Zsengellér, Christa Flechtenmacher, Siegfried Hagl, Csaba Szabó

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: To investigate the effects of PARP inhibition on cardiac and pulmonary function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Methods: Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n=6), or the potent PARP-inhibitor PJ34 (5 mg/kg; n=6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodium-nitroprusside and pulmonary function were also determined. The cardiac and pulmonary activation of PARP was detected by poly(ADP-ribose) immunohistochemistry. Results: Administration of PJ34 led to a significantly better recovery of left and right ventricular systolic function (P<0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the PJ34 treated group (P<0.05). PJ34 treatment preserved the acetylcholine-induced increases in coronary and pulmonary blood (P<0.05). Pulmonary function in terms of alveolar arterial oxygen difference was better maintained in the PJ34 treated animals (P<0.05). Immunohistochemical staining revealed PARP activation after cardiopulmonary bypass in both the heart and lung, which was prevented by PJ34. Conclusions: PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and protects against the development of remote pulmonary injury during cardiopulmonary bypass.

Original languageEnglish
Pages (from-to)825-832
Number of pages8
JournalEuropean Journal of Cardio-Thoracic Surgery
Volume25
Issue number5
DOIs
Publication statusPublished - May 1 2004

Keywords

  • Cardiopulmonary bypass
  • Endothelial function
  • PARP inhibition
  • Reperfusion injury

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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