TNFalpha in ischemia/reperfusion injury and heart failure.

During myocardial ischemia, both the myocardial and serum TNFalpha concentrations are rapidly increased within the area at risk. With prolongation of ischemia and development of cardiomyocyte necrosis, the TNFalpha concentration increases also in the surrounding viable portions of the myocardium. Indeed, in the scenario of myocardial ischemia/reperfusion, treatment with TNFalpha antibodies reduced the extent of myocardial infarction in rabbits and attenuated the contractile dysfunction following microembolization in dogs. In the latter studies, the serum TNFalpha concentration remained unaltered thereby supporting the notion of a direct action of TNFalpha at the level of cardiomyocytes during ischemia/reperfusion. In heart failure, the serum TNFalpha concentration is also increased, and in patients with advanced heart failure the serum TNFalpha concentration is an independent predictor of mortality. The origin of the increased serum TNFalpha concentration is not clearly identified yet, but TNFalpha derived from the heart and peripheral organs contributes to the increased serum TNFalpha concentration. Treatment with TNFalpha antibodies in the clinical scenario, however, did not improve the prognosis of heart failure patients.