Aprotinin preserves myocardial biochemical function during cold storage through suppression of tumor necrosis factor

Objective: inflammatory cytokines,particularly tumor necrosis factor, contr ibute to myocardial dysfunction after ischemia-reperfusion injury Aprotinin may improve outcomes in cardiac surgery through suppression of inflammator y mediators, We hypothesized that aprotinin may exert its beneficial effect s through suppression of tumor necrosis factor alpha. Methods: Adult rat he arts were precision cut into slices with a thickness of 200 mu m and stored in crystalloid cardioplegic solution alone or with one of the following ad ditions: aprotinin or tumor necrosis factor alpha, aprotinin plus tumor nec rosis factor alpha, a monoclonal antibody to tumor necrosis factor alpha, o r a polyclonal antibody to the tumor necrosis factor alpha receptor Myocard ial biochemical function was assessed by adenosine triphosphate content and capacity for protein synthesis immediately after slicing (0 hours) and aft er 2, 4, and 6 hours of storage at 4 degrees C. The content of tumor necros is factor alpha was measured by an enzyme-linked immunosorbent assay. Six s lices were assayed at each time point for each solution. The data were anal yzed by analysis of variance and are expressed as the mean +/- standard dev iation. Results: When stored in cardioplegic solution containing aprotinin, the heart slices demonstrated (1) an increase in adenosine triphosphate co ntent and protein synthesis (P < .0001), (2) a decrease in intramyocardial generation of tumor necrosis factor alpha (P less than or equal to .0311), and (3) a decrease in uptake of tumor necrosis factor alpha into the myocar dium (P less than or equal to .002) compared with storage in cardioplegic s olution alone. The presence of an antibody to tumor necrosis factor alpha o r an antibody to the tumor necrosis factor alpha receptor in cardioplegic s olution increased intramyocardial adenosine triphosphate content and protei n synthesis (P less than or equal to .0001), Conclusions: Aprotinin preserv es myocardial biochemical function during cold storage. This preservation o f biochemical function is mediated through: suppression of the release, upt ake, and activity of tumor necrosis factor alpha.