Mesenteric injury after cardiopulmonary bypass: role of poly(adenosine 5'-diphosphate-ribose) polymerase.
OBJECTIVE
To investigate the effects of the ultrapotent poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitor INO-1001 on cardiac and mesenteric function during reperfusion in an experimental model of cardiopulmonary bypass with cardioplegic arrest.


METHODS
Prospective, randomized, and blinded experimental study.


METHODS
Research laboratory.


METHODS
: Twelve anesthetized dogs underwent cardiopulmonary bypass with hypothermic cardioplegic cardiac arrest.


METHODS
After 60 mins of hypothermic cardiac arrest, either PARP inhibitor INO-1001 (1 mg/kg, n = 6) or vehicle (control, n = 6) was administered during reperfusion.


RESULTS
Left ventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and mesenteric blood flow and vasodilatory responses to acetylcholine and sodium nitroprusside as well as mesenteric lactate and creatinine phosphokinase release were also determined. The administration of INO-1001 led to a significantly improved recovery of left ventricular systolic function (p < .05) after 60 mins of reperfusion. Coronary and mesenteric blood flow were also significantly higher in the INO-1001 group (p < .05). Although the vasodilatory response to sodium nitroprusside was similar in both groups before and after cardiopulmonary bypass and similar in response to acetylcholine before cardiopulmonary bypass, PARP-inhibited dogs had lower mesenteric vascular resistance after cardiopulmonary bypass (p < .05). Mesenteric lactate and creatinine phosphokinase release was significantly lower in the PARP inhibitor treated group (p < .05).


CONCLUSIONS
PARP inhibition with INO-1001 improves the recovery of myocardial function and prevents mesenteric vascular dysfunction and tissue injury after cardiopulmonary bypass with hypothermic cardiac arrest.
Szabó
Gábor
G
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Soós
Pál
P
Mandera
Susanne
S
Heger
Ulrike
U
Flechtenmacher
Christa
C
Seres
Leila
L
Zsengellér
Zsuzsanna
Z
Sack
Falk-Udo
FU
Szabó
Csaba
C
Hagl
Siegfried
S
D000818:Animals; D001707:Biopsy, Needle; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008643:Mesentery / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases