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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 44, 2015 - Issue 1
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Original Articles

Dual effects of tumor necrosis factor alpha on myocardial injury following prolonged hypoperfusion of the heart

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Abstract

Objective: To examine the dose response of TNFα in an ex vivo rat model of myocardial ischemia reperfusion. Methods and Results: Seventy-two rat hearts were mounted on Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solutions. Ischemia was induced by reducing the perfusate flow rate. During reperfusion, incremental doses of recombinant TNFα were infused as a part of perfusate. TNFα was blocked with monoclonal TNFα antibody. Myocardial function was measured by dP/dT and relaxation time (IVRT). Cellular injury was assessed by released myoglobin and tissue concentration of malondialdehyde activity of the heart homogenates. Baseline +dP/dT was 1645 ± 125 mmHg/sec, –dP/dT was 945 ± 73 mmHg/sec and IVRT was 65 ± 5 msec. At the conclusion of reperfusion period, lower doses of TNFα increased +dP/dT and lowered IVRT. In contrast, the higher doses of TNFα decreased +dP/dT and prolonged IVRT. Pretreating the hearts with monoclonal TNFα antibody completely abolished the effects of TNFα on myocardial contractility and relaxation comparable to ischemia controls. Conclusion: Low dose TNFα improved myocardial function and decreased resultant cellular injury while high dose TNFα decreased myocardial function and increased myocardial injury following ischemia and reperfusion.

Declaration of interest

This study is supported by a grant from American Heart Association.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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