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 Szabo

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 (US)
Pages (from-to)825-832
Number of pages8
JournalEuropean Journal of Cardio-thoracic Surgery
Volume25
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Cardiopulmonary Bypass
Canidae
Lung
Reperfusion
Heart Arrest
Acetylcholine
Poly Adenosine Diphosphate Ribose
Right Ventricular Function
Lung Injury
Nitroprusside
Vasodilator Agents
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
Theoretical Models
Catheters
Hemodynamics
Immunohistochemistry
Dogs
Staining and Labeling
Oxygen

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass. / Szabó, Gábor; Soós, Pál; Bährle, Susanne; Zsengellér, Zsuzsanna; Flechtenmacher, Christa; Hagl, Siegfried; Szabo, Csaba.

In: European Journal of Cardio-thoracic Surgery, Vol. 25, No. 5, 05.2004, p. 825-832.

Research output: Contribution to journalArticle

Szabó, Gábor ; Soós, Pál ; Bährle, Susanne ; Zsengellér, Zsuzsanna ; Flechtenmacher, Christa ; Hagl, Siegfried ; Szabo, Csaba. / Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass. In: European Journal of Cardio-thoracic Surgery. 2004 ; Vol. 25, No. 5. pp. 825-832.
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