BACKGROUND Mesenteric ischemia/reperfusion (I/R) is a common problem in critically ill patients and is frequently associated with myocardial dysfunction. Several potential mechanisms have been proposed to be involved in the myocardial dysfunction associated with mesenteric I/R, including nuclear factor kappa B (NF kappaB)-mediated tumor necrosis factor alpha (TNF-alpha) release leading to cardiodepression. Thus, we sought to investigate the effect of NF kappaB inhibition on mesenteric I/R-associated myocardial dysfunction in a large animal model (dog). MATERIALS AND METHODS A total of 21 mongrel dogs were anesthetized and mechanically ventilated. Animals were instrumented with a Swan-Ganz Catheter, left ventricle (LV) pressure manometer, and ultrasonic crystals. Mesenteric I/R consisted of 60 min of ischemia followed by 180 min of reperfusion. Seven animals received pyrrolidine dithiocarbamate (PDTC, 100 mg/kg) prior to mesenteric I/R (I/R PDTC). Another group of animals (n = 7) without mesenteric ischemia received PDTC following baseline measurements and served as control for the effect of PDTC alone (PDTC). Preload recruitable stroke work, +/-dp/dt(max), isovolumic relaxation (tau), and cardiac output were measured. Myocardial tissue was analyzed for NF kappaB activity, TNF-alpha production, and myocardial apoptosis. RESULTS Mesenteric I/R impaired both LV systolic and diastolic function. Administration of PDTC worsened LV function impairment following I/R. In addition, PDTC resulted in decreased LV function even without mesenteric I/R. NF kappaB, TNF-alpha, and myocardial apoptosis were not different among the groups. CONCLUSIONS Mesenteric I/R affects LV function independent of NF kappaB and TNF-alpha pathways. PDTC acts as a cardiac depressant through a thus far unknown mechanism. Therefore, evaluation of cardiac and hemodynamic function in experimental setups using PDTC has to be carefully interpreted.