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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/H2972    most recent 01039.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Andrási, T. B. Articles by Hagl, S. Search for Related Content PubMed PubMed Citation Articles by Andrási, T. B. Articles by Hagl, S.

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

¹Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; ²Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital, Dresden, Germany; and ³Department 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