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-nitroprusside (SNP) were expressed as percent change of MVR. In addition, mesenteric creatine kinase (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.


CONCLUSIONS
PARP inhibition prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.
Szabó
G
G
Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Gabor.Szabo@urz.uni-heidelberg.de
Seres
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L
Soós
P
P
Flechtenmacher
C
C
Zsengellér
Z
Z
Sack
F-U
FU
Szabó
C
C
Hagl
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000293:injuries* / Q000503:physiopathology; D008642:Mesenteric Veins / Q000293:injuries* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects* / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019344:Lactic Acid; D011065:Poly(ADP-ribose) Polymerases; D003402:Creatine Kinase; D000109:Acetylcholine