Human myocardial tissue TNFα expression following acute global ischemia in vivo

Although human myocardial TNF alpha levels are increased during the ischemia associated with chonic heart failure, it remains unknown whether an acute global ischemic insult further increases TNF alpha expression in human cardiac myocytes. To study this, biopsies of human myocardium were obtained before and after cardiopulmonary bypass (in vivo acute global ischemia). and myocardial TNF alpha levels were determined by ELISA and cytotoxicity assay (WEHI-164 clone 13 cell line). TNF alpha was immunolocalized by immunohistochemistry. Results indicate that cardiopulmonary bypass induces an increase in human myocardial TNF alpha by both ELISA and cytotoxicity assays. Immunolocalization revealed that prior to cardiopulmonary bypass TNF alpha was located predominantly in the myocardial interstitial cells: however, following bypass, increased TNF alpha was observed in the cardiocytes themselves. Locally-produced myocardial TNF alpha may be an important contributor to myocardial functional depression and injury following acute ischemia. Targeted anti-TNF alpha therapy in the treatment of cardiac ischemic injury may further elucidate its clinical relevance. (C) 1998 Academic Press