Increased myocardial gene expression of tumor necrosis factor-alpha and nitric oxide synthase-2: a potential mechanism for depressed myocardial function in hibernating myocardium in humans
Abstract
Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P<0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-alpha and nitrite levels from baseline to 3 months after surgery correlated inversely with bo...Continue Reading
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