TNF-α is required for late ischemic preconditioning but not for remote preconditioning of trauma

Background. Ischemic preconditioning (IPC) and remote IPC are cardioprotective phenomena in which ischemia of the myocardium or of a remote tissue, respectively, induces cardioprotection. Despite clinical evidence that surgical trauma can remotely affect myocardial infarction, to date there are no basic science studies addressing the effect of nonischemic trauma at distant sites upon cardiac ischemia/reperfusion (I/R) injury. The objectives of this study were to determine the effects of nonischemic remote surgical trauma upon infarct size after myocardial I/R and to determine the effects of TNF-alpha ablation upon cardioprotective phenomena. Materials and methods. A minimally traumatic mouse model was used to ascertain the effect of remote nonischemic surgical trauma upon I/R injury. TNF-a knockout mice were employed to determine the effect of TNF-a ablation. Results. Carotid artery vascular surgery remotely exacerbates cardiac I/R injury increasing infarct size by 287% (remote cardiac injury or RCI). Nonischemic, nonvascular trauma (abdominal incision) results in remote preconditioning of trauma (RPCT), decreasing infarct size by 81% (early phase) and 40% (late phase) relative to controls. Finally, TNF-alpha is required for late IPC but is not necessary for RCI or for RPCT. Conclusions. We show that late IPC is TNF-alpha-dependent and describe two unique TNF-alpha-independent remote effects of nonischemic trauma upon myocardial infarction. Understanding the mechanism of these remote effects will allow the development of novel therapies for the treatment of ischemic heart disease. RPCT and TNF-alpha ablation have an additive protective effect suggesting that combinations of complementary approaches may be a useful strategy for maximizing the clinical efficacy of cardioprotective therapies. (C) 2004 Elsevier Inc. All rights reserved.