TNFα in ischemia/reperfusion injury and heart failure

Abstract.

During myocardial ischemia, both the myocardial and serum TNFα concentrations are rapidly increased within the area at risk. With prolongation of ischemia and development of cardiomyocyte necrosis, the TNFα concentration increases also in the surrounding viable portions of the myocardium. Indeed, in the scenario of myocardial ischemia/reperfusion, treatment with TNFα antibodies reduced the extent of myocardial infarction in rabbits and attenuated the contractile dysfunction following microembolization in dogs. In the latter studies, the serum TNFα concentration remained unaltered thereby supporting the notion of a direct action of TNFα at the level of cardiomyocytes during ischemia/reperfusion.

In heart failure, the serum TNFα concentration is also increased, and in patients with advanced heart failure the serum TNFα concentration is an independent predictor of mortality. The origin of the increased serum TNFα concentration is not clearly identified yet, but TNFα derived from the heart and peripheral organs contributes to the increased serum TNFα concentration. Treatment with TNFα antibodies in the clinical scenario, however, did not improve the prognosis of heart failure patients.