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

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.