Mesenteric injury after cardiopulmonary bypass: Role of poly(adenosine 5′-diphosphate-ribose) polymerase

o date, the majority of routinecardiac surgery is performedusing cardiopulmonary bypass(CPB) with cardioplegic ar-rest. Despite technological and medicaladvances, CPB still imposes considerablephysiologic stress on the patient (1).Independent of the technique of cardio-plegia, temporary cardiac dysfunctioncan be observed frequently as a conse-quence of ischemia/reperfusion injury(2). In addition, CPB is also known toinduce a systemic inflammatory reac-tion (3–5) with free radical release (6)leading to secondary organ injury.There is an evidence that pulmonary(7), renal (8) or gastrointestinal (9) in-jury may occur in the context of cardiacsurgery as a consequence of CPB-induced inflammatory reaction and re-duced organ perfusion (6, 10) rangingfrom subclinical functional changes inmost patients to full-blown clinicalcomplications. Gastrointestinal compli-cations have a low incidence, between1% and 3% (9, 11, 12). Once a gastro-intestinal complication occurs, how-ever, the overall mortality rate rangesfrom 13.5% to 72%. In particular, pa-tients with gastric bleeding or cholecys-titis are most likely to survive, whereasthe lethality of mesenteric ischemia isextremely high (9, 12). In previousstudies (6, 13), we showed that intesti-nal injury can be observed during rou-tine CPB as a result of hypoperfusion,impaired endothelial function, and freeradical generation.Poly(adenosine 5'-diphosphate-ribose)polymerase (PARP) is an abundant nu-clear enzyme of eukaryotic cells. Freeradical production and related cytotoxic-ity during inflammation or ischemia/reperfusion may lead to DNA strand-breakage that activates PARP. ActivatedPARP catalyzes an energy-consuming cy-cle by transferring adenosine 5'-diphos-phate (ADP) ribose units to nuclear pro-teins. The results of this process are rapiddepletion of the intracellular oxidizednicotinamide adenine dinucleotide andadenosine 5'-triphosphate pools, whichslowstherateofglycolysisandmitochon-drial respiration leading to cell necrosis(14). Both the genetic disruption of thePARP pathway and the pharmacologic