Abstract OBJECTIVES The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-α (TNFα). METHODS Twelve young pigs were assigned to a temperature (T°) regimen during CPB: moderate hypothermia (T°: 28°C; n = 6) and normothermia (T°: 37°C; n = 6). Intra-myocardial TNFα- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS Synthesis of IL10 was significantly higher, while that of TNFα was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFα synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.