Myocardial Function After Gut Ischemia/Reperfusion

Does NFκB Play a Role?

Uwe M. Fischer, Ravi Radhakrishnan, Karen S. Uray, Hasen Xue, Charles S. Cox

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 (NFκB)-mediated tumor necrosis factor alpha (TNF-α) release leading to cardiodepression. Thus, we sought to investigate the effect of NFκB 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 NFκB activity, TNF-α 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. NFκB, TNF-α, and myocardial apoptosis were not different among the groups. Conclusions: Mesenteric I/R affects LV function independent of NFκB and TNF-α pathways. PDTC acts as a cardiac depressant through a thus far unknown mechanism. Therefore, evalutation of cardiac and hemodynamic function in experimental setups using PDTC has to be carefully interpreted.

Original languageEnglish (US)
Pages (from-to)264-270
Number of pages7
JournalJournal of Surgical Research
Volume152
Issue number2
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

NF-kappa B
Reperfusion
Ischemia
Heart Ventricles
Dogs
Apoptosis
prolinedithiocarbamate
Myocardial Reperfusion
Mesenteric Ischemia
R Factors
Anti-Arrhythmia Agents
Critical Illness
Ultrasonics
Cardiac Output
Catheters
Animal Models
Tumor Necrosis Factor-alpha
Hemodynamics
Stroke
Pressure

Keywords

  • cardiac function
  • mesenteric ischemia/reperfusion
  • NFκB
  • TNF-α

ASJC Scopus subject areas

  • Surgery

Cite this

Myocardial Function After Gut Ischemia/Reperfusion : Does NFκB Play a Role? / Fischer, Uwe M.; Radhakrishnan, Ravi; Uray, Karen S.; Xue, Hasen; Cox, Charles S.

In: Journal of Surgical Research, Vol. 152, No. 2, 04.2009, p. 264-270.

Research output: Contribution to journalArticle

Fischer, Uwe M. ; Radhakrishnan, Ravi ; Uray, Karen S. ; Xue, Hasen ; Cox, Charles S. / Myocardial Function After Gut Ischemia/Reperfusion : Does NFκB Play a Role?. In: Journal of Surgical Research. 2009 ; Vol. 152, No. 2. pp. 264-270.
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