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; Szabó, Csaba
May 2004
European Journal of Cardio-Thoracic Surgery;May2004, Vol. 25 Issue 5, p825
Academic Journal
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.


Related Articles

  • Tetrahydrobiopterin improves cardiac and pulmonary function after cardiopulmonary bypass Szabó, Gábor; Seres, Leila; Soós, Pál; Gorenflo, Matthias; Merkely, Béla; Horkay, Ferenc; Karck, Matthias; Radovits, Tamás // European Journal of Cardio-Thoracic Surgery;Sep2011, Vol. 40 Issue 3, p695 

    Abstract: Objective: Tetrahydrobiopterin (BH4) is an important cofactor of endogenous nitric oxide synthesis. In the present preclinical study, we investigated the effects of BH4 on cardiac and pulmonary function during early reperfusion in an experimental model of cardioplegic arrest and...

  • Reoperative Coronary Bypass Surgery Using Normothermic Cardiopulmonary Bypass: Comparison with First-Time Procedures. Ott, Richard A.; Steedman, Robert; Eugene, John; Dajee, Amrit; Ott, Wendy; Tanner, Teresa // American Surgeon;Dec2001, Vol. 67 Issue 12, p1190 

    Redo coronary artery bypass grafting (CABG) is characterized by increased patient risk compared with first-time CABG. The reason for higher risk is not completely understood but it is logically related to inadequate myocardial preservation evidenced by the higher incidence of postoperative...

  • Na[sup +]/H[sup +] exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass. Eichler, Wolfgang; Bechtel, Matthias J. F.; Klaus, Stephan; Heringlake, Matthias; Hernandez, Mario; Toeber, Kai; Klotz, Karl-Friedrich; Bartels, Claus // Perfusion;Jan2004, Vol. 19 Issue 1, p33 

    The purpose of the present study was to evaluate the potential of the Na[sup +]/H[sup +] exchange inhibitor cariporide to protect the lung from injury after cardiopulmonary bypass (CPB). In a randomized placebo-controlled study, 16 pigs were subjected to CPB for 75 min. Administration of vehicle...

  • Leukocyte filtration and aprotinin: synergistic anti-inflammatory protection. Olivencia-Yurvati, Albert H.; Wallace, Neil; Ford, Sheila; Mallet, Robert T. // Perfusion;Jan2004 Supplement 1, Vol. 19, p13 

    Cardiopulmonary bypass activates an array of cellular and humoral inflammatory mechanisms that culminate in diverse or organ-specific injury. A manifestation of inflammatory injury to the heart, atrial fibrillation ranks among the most frequent and potentially life-threatening postsurgical...

  • Usefulness of Intraoperative Color Doppler Ultrasonography in Decision Making Regarding Conversion of an Accessory Hepatic Vein after a Fontan-Type Operation. Maeda, K.; Murakami, A.; Takaoka, T.; Takamoto, S.; Sano, K.; Makuuchi, M. // Pediatric Cardiology;Jul/Aug2004, Vol. 25 Issue 4, p414 

    An accessory hepatic vein (AHV) after a Fontan-type operation will result in progressive desaturation if left intact. We report a case in which intraoperative color Doppler ultrasonography revealed the absence of AHV flow and reversed portal vein flow when the AHV was clamped, suggesting that...

  • Ventilation prevents pulmonary endothelial dysfunction and improves oxygenation after cardiopulmonary bypass without aortic cross-clamping Lamarche, Yoan; Gagnon, Julie; Malo, Olivier; Blaise, Gilbert; Carrier, Michel; Perrault, Louis P. // European Journal of Cardio-Thoracic Surgery;Sep2004, Vol. 26 Issue 3, p554 

    Objective: Endothelial dysfunction of the pulmonary arterial tree occurring after cardiopulmonary bypass (CPB) contributes to pulmonary hypertension and respiratory failure in the postoperative period. The goal of the present study was to characterize the alterations of endothelial cell signal...

  • PULMONARY EMBOLECTOMY. Sharp, William V.; Ruf, Walter // Vascular Surgery;Mar1969, Vol. 3 Issue 1, p18 

    A case of massive pulmonary embolism after cataract extraction is reported. Cardiac arrest occurred in the emergency room and, after resuscitation, a successful pulmonary embolectomy was performed with the aid of cardiopulmonary bypass. The incidence of thromboembolism at Akron City Hospital was...

  • Does Combined Antegrade–Retrograde Cardioplegia Have Any Superiority Over Antegrade Cardioplegia? Radmehr, Hassan; Soleimani, Aliakbar; Tatari, Hassan; Salehi, Mehrdad // Heart, Lung & Circulation;Dec2008, Vol. 17 Issue 6, p475 

    Background: In a prospective randomised clinical study we assessed and compared antegrade vs. combined antegrade–retrograde cardioplegia in patients who underwent elective coronary artery by pass grafting. Methods: Between March 2006 and January 2007, 87 consecutive patients were randomly...

  • 812 Systolic and diastolic ventricular performance after normothermic CPB with intermittent antegrade warm blood cardioplegia. Tulner, S.; Klautz, R.J.M.; Engbers, F.H.M.; Bax, J.; Van der Wal, E.E.; Dion, R.A.E.; Steendijk, P. // European Journal of Heart Failure. Supplements;Jun2004, Vol. 2 Issue 1, p178 

    An abstract of the study "Systolic and diastolic ventricular performance after normothermic CPB with intermittent antegrade warm blood cardioplegia," by S. Tulner et al. is presented.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics