Anti-tumor necrosis factor-alpha antibodies prevent myocardial ischemic-reperfusion injury

This study assesses the importance of locally-released/paracrine myocardial tumor necrosis factor-alpha (TNF) in the evolution of post-ischemic myocardial dysfunction. Significant amounts of TNF were detected in the effluent of the isolated rat heart undergoing cardioplegic arrest and prolonged ischemia. Immunohistochemical studies localized TNF to cardiac myocytes, and to vascular endothelial cells. We have proven here that this paracrine TNF release plays a dominant role in the ischemia-reperfusion injury, as neutralization with specific monoclonal antibodies (mAb) against this cytokine (given before ischemia, in the cardioplegic solution) completely eliminated TNF from the effluent, preserved myocardial structure and improved the post-ischemic myocardial function.