Poly-ADP-Ribose Polymerase Inhibition Reduces Mesenteric Injury after Cardiopulmonary Bypass[*]

Abstract

Background: We investigated the effects of PARS inhibition on intestinal injury in a canine model of cardiopulmonary bypass (CPB). Methods: Twelve dogs underwent 90 minutes of hypothermic CPB. 6 dogs received 5 mg/kg PJ34, a selective PARP inhibitor during CPB, 6 vehicle-treated animals served as controls. Mesenteric blood flow (MBF) and mesenteric vascular resistance (MVR) were measured before and 60 minutes after weaning from CPB. Endothelium-dependent vasorelaxation to acetylcholine (ACH) and endothelium-independent vasorelaxation to sodium-nitroprussid (SNP) were expressed as percent change of MVR. In addition, mesenteric creatinkinase (CK) and lactate release were determined. Results: Baseline hemodynamics, MBF, response to ACH (- 41 ± 3 vs. - 55 ± 6 %) and SNP (- 60 ± 2 vs. - 56 ± 4 %) did not differ significantly between the groups. The response to ACH decreased significantly in the control group while it remained unchanged in the PJ34 group (- 29 ± 5 vs. - 46 ± 9 %, p < 0.05). The response to SNP did not change. Mesenteric CK release (325 ± 99 vs. 16 ± 10 U/l, p < 0.05) and lactate production (0.96 ± 0.17 vs. 0.4 ± 0.2 mmol/l, p < 0.05) were significantly lower in the PJ34 group. Conclusion: PARP inhibition prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.

Poly (ADP-ribose) polymerase - cardiopulmonary bypass - mesenteric injury

References

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1 This study was presented at the 4th Joint Meeting of the German, Austrian, and Swiss Society for Thoracic and Cardiovascular Surgery, Hamburg, February 15 - 18, 2004

2 Gábor Szabó and Leila Seres contributed equally to this work