title: Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass.
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.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Germany. dzsi@hotmail.com
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Pál
authors.initials: P
authors.lastname: Soós
authors.forename: Susanne
authors.initials: S
authors.lastname: Bährle
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Zsengellér
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hagl
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D014664:Vasodilation
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases