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Myocardial function after gut ischemia/reperfusion: does NF kappaB play a role?
Uwe M Fischer1, Ravi S Radhakrishnan, Karen S Uray
1Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
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.
Insights
Mesenteric ischemia/reperfusion impairs heart function independently of NF kappaB and TNF-alpha. Pyrrolidine dithiocarbamate (PDTC) worsens cardiac function through an unknown mechanism.
Area of Science:
- Cardiology
- Gastroenterology
- Critical Care Medicine
Background:
- Mesenteric ischemia/reperfusion (I/R) is a critical condition linked to myocardial dysfunction.
- Nuclear factor kappa B (NF kappaB)-mediated tumor necrosis factor alpha (TNF-alpha) release is a proposed mechanism for this cardiac dysfunction.
Purpose of the Study:
- To investigate the effect of NF kappaB inhibition on myocardial dysfunction following mesenteric I/R in a canine model.
- To determine if NF kappaB and TNF-alpha pathways mediate cardiac dysfunction in mesenteric I/R.
Main Methods:
- Mongrel dogs underwent mesenteric I/R (60 min ischemia, 180 min reperfusion).
- Pyrrolidine dithiocarbamate (PDTC) was administered to inhibit NF kappaB.
- Left ventricular (LV) function, cardiac output, and myocardial tissue markers (NF kappaB, TNF-alpha, apoptosis) were assessed.
Main Results:
- Mesenteric I/R significantly impaired LV systolic and diastolic function.
- PDTC administration exacerbated LV dysfunction post-I/R and also depressed LV function independently.
- No significant differences in NF kappaB activity, TNF-alpha production, or myocardial apoptosis were observed between groups.
Conclusions:
- Mesenteric I/R-induced LV dysfunction occurs independently of NF kappaB and TNF-alpha pathways.
- PDTC exhibits cardiac depressant effects via an unidentified mechanism.
- Caution is advised when interpreting cardiac and hemodynamic data from experiments using PDTC.
