Objective: Inflammatory cytokines, particularly tumor necrosis factor, contribute to myocardial dysfunction after ischemia-reperfusion injury. Aprotinin may improve outcomes in cardiac surgery through suppression of inflammatory mediators. We hypothesized that aprotinin may exert its beneficial effects through suppression of tumor necrosis factor α. Methods: Adult rat hearts were precision cut into slices with a thickness of 200 μm and stored in crystalloid cardioplegic solution alone or with one of the following additions: aprotinin or tumor necrosis factor α, aprotinin plus tumor necrosis factor α, a monoclonal antibody to tumor necrosis factor α, or a polyclonal antibody to the tumor necrosis factor α receptor. Myocardial biochemical function was assessed by adenosine triphosphate content and capacity for protein synthesis immediately after slicing (0 hours) and after 2, 4, and 6 hours of storage at 4°C. The content of tumor necrosis factor α was measured by an enzyme-linked immunosorbent assay. Six slices were assayed at each time point for each solution. The data were analyzed by analysis of variance and are expressed as the mean ± standard deviation. Results: When stored in cardioplegic solution containing aprotinin, the heart slices demonstrated (1) an increase in adenosine triphosphate content and protein synthesis (P < .0001), (2) a decrease in intramyocardial generation of tumor necrosis factor α (P ≤ .0311), and (3) a decrease in uptake of tumor necrosis factor α into the myocardium (P ≤ .002) compared with storage in cardioplegic solution alone. The presence of an antibody to tumor necrosis factor α or an antibody to the tumor necrosis factor α receptor in cardioplegic solution increased intramyocardial adenosine triphosphate content and protein synthesis (P < .0001). Conclusions: Aprotinin preserves myocardial biochemical function during cold storage. This preservation of biochemical function is mediated through suppression of the release, uptake, and activity of tumor necrosis factor α.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine