Human Myocardial Tissue TNFαExpression Following Acute Global IschemiaIn Vivo

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