Myocardial function after gut ischemia/reperfusion: does NF kappaB play a role?
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).


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.
Fischer
Uwe M
UM
Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Radhakrishnan
Ravi S
RS
Uray
Karen S
KS
Xue
Hasen
H
Cox
Charles S
CS
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D016923:Cell Death; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007601:Jugular Veins / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D016328:NF-kappa B / Q000502:physiology*; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology*; D012121:Respiration, Artificial; D013318:Stroke Volume / Q000502:physiology; D013599:Systole
D016328:NF-kappa B