Poly(ADP-ribose) polymerase inhibitor PJ-34 reduces mesenteric vascular injury induced by experimental cardiopulmonary bypass with cardiac arrest

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 6; pp. H2972 - H2978
• Main Authors: Andrasi, Terezia B, Blazovics, Anna, Szabo, Gabor, Vahl, Christian F, Hagl, Siegfried
• Format: Journal Article
• Language: English
• Published: United States 01.06.2005
• Subjects: Animals; Cardiopulmonary Bypass - methods; Disease Models, Animal; Dogs; Enzyme Inhibitors - pharmacology; Heart Arrest - physiopathology; Heart Arrest - prevention & control; Hemodynamics; Myocardial Reperfusion; Peroxidase - blood; Phenanthrenes - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors; Splanchnic Circulation - drug effects; Splanchnic Circulation - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01039.2004

1 Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; 2 Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital, Dresden, Germany; and 3 Department of Internal Medicine, Semmelweis University, Budapest, Hungary Submitted 10 October 2004 ; accepted in final form 17 January 2005 The aim of this study was to investigate effects of poly(ADP-ribose) polymerase (PARP) inhibition on mesenteric vascular function and metabolism in an experimental model of cardiopulmonary bypass (CPB) with cardiac arrest. Twelve anesthetized dogs underwent 90-min hypothermic CPB. After 60 min of cardiac arrest, reperfusion was started for 40 min following application of either saline vehicle (control, n = 6) or a potent PARP inhibitor, PJ-34 (10 mg/kg iv bolus and 0.5 mg·kg –1 ·min –1 infusion for 20 min, n = 6). PJ-34 led to better recovery of cardiac output (2.2 ± 0.1 vs. 1.8 ± 0.2 l/min in control) and mesenteric blood flow (175 ± 38 vs. 83 ± 4 ml/min, P < 0.05 vs. control) after reperfusion. The impaired vasodilator response of the superior mesenteric artery to acetylcholine, assessed in the control group after CPB (–32.8 ± 3.3 vs. –57.6 ± 6.6% at baseline, P < 0.05), was improved by PJ-34 (–50.3 ± 3.6 vs. –54.3 ± 4.1% at baseline, P < 0.05 vs. control). Although plasma nitrate/nitrite concentrations were not significantly different between groups, mesenteric nitric oxide synthase activity was increased in the PJ-34 group ( P < 0.05). Moreover, the treated group showed a marked attenuation of mesenteric venous plasma myeloperoxidase levels after CPB compared with the control group (75 ± 1 vs. 135 ± 9 ng/ml, P < 0.05). Pharmacological PARP inhibition protects against development of post-CPB mesenteric vascular dysfunction by improving hemodynamics, restoring nitric oxide production, and reducing neutrophil adhesion. endothelial function; nitric oxide; neutrophil adhesion; hemodynamics Address for reprint requests and other correspondence: T. B. Andrási, Dept. of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus Univ. Hospital, Fetscherstrasse 74, Haus 59, 01307 Dresden, Germany (E-mail: tean74{at}hotmail.com )