BACKGROUND: The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the myocardium itself is capable of producing TNF-alpha in response to endotoxin, it is unknown whether there is an increase in myocardial tissue TNF-alpha levels after ischemia-reperfusion injury. We hypothesized that ischemia-reperfusion induces the production of TNF-alpha by the heart. METHODS: To avoid blood-borne TNF-alpha as a potentially confounding variable, we examined myocardial TNF-alpha production in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Isolated rat hearts were perfused with crystalloid solution and subjected to ischemia-reperfusion. Postischemic myocardial TNF-alpha was measured using an enzyme-linked immunosorbent assay and correlated with developed pressure, coronary flow, end-diastolic pressure, and creatine kinase loss (assay of activity in coronary effluent). RESULTS: Ischemia-reperfusion induced a marked increase in myocardial TNF-alpha that was associated with decreased myocardial contractility and coronary flow and with increased end-diastolic pressure and postischemic creatine kinase loss. CONCLUSIONS: The heart produces TNF-alpha in response to ischemia-reperfusion. Ischemia-induced TNF-alpha production may contribute to postischemic myocardial stunning, necrosis, or both. Strategies designed to limit ischemia-induced myocardial TNF-alpha production may have therapeutic utility in the settings of planned myocardial ischemic events.
BACKGROUND: The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the myocardium itself is capable of producing TNF-alpha in response to endotoxin, it is unknown whether there is an increase in myocardial tissue TNF-alpha levels after ischemia-reperfusion injury. We hypothesized that ischemia-reperfusion induces the production of TNF-alpha by the heart. METHODS: To avoid blood-borne TNF-alpha as a potentially confounding variable, we examined myocardial TNF-alpha production in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Isolated rat hearts were perfused with crystalloid solution and subjected to ischemia-reperfusion. Postischemic myocardial TNF-alpha was measured using an enzyme-linked immunosorbent assay and correlated with developed pressure, coronary flow, end-diastolic pressure, and creatine kinase loss (assay of activity in coronary effluent). RESULTS:Ischemia-reperfusion induced a marked increase in myocardial TNF-alpha that was associated with decreased myocardial contractility and coronary flow and with increased end-diastolic pressure and postischemic creatine kinase loss. CONCLUSIONS: The heart produces TNF-alpha in response to ischemia-reperfusion. Ischemia-induced TNF-alpha production may contribute to postischemic myocardial stunning, necrosis, or both. Strategies designed to limit ischemia-induced myocardial TNF-alpha production may have therapeutic utility in the settings of planned myocardial ischemic events.
Authors: Rama Surya Prakash Perepu; David E Dostal; Carlos Garcia; Richard H Kennedy; Rajat Sethi Journal: Mol Cell Biochem Date: 2011-09-27 Impact factor: 3.396
Authors: John Cha; Zhiping Wang; Lihua Ao; Ning Zou; Charles A Dinarello; Anirban Banerjee; David A Fullerton; Xianzhong Meng Journal: Ann Thorac Surg Date: 2008-05 Impact factor: 4.330