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