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

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.