Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8, and anti unflammatory cytokines, such as interleukin-10, may play an important role in patient responses to cardiopulmonary bypass. We sought to define whether the myocardium and the lungs serve as important sources of these cytokines under conditions of cardiopulmonary bypass. Ten patients (age 64 +/- 3 years, mean +/- standard error of the mean) undergoing elective coronary artery bypass grafting were monitored with an arterial catheter, a coronary sinus catheter, and pulmonary artery catheter. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured simultaneously in peripheral arterial blood, coronary sinus blood, and mixed venous blood before heparin administration, 1 minute before aortic crossclamping, 5 minutes after aortic declamping, and at 0.5, 1, 1.5 and 2 hours after aortic declamping. The durations of cardiopulmonary bypass and aortic crossclamping were 114 +/- 9 and 64 +/- 5 minutes, respectively. Levels of tumor necrosis factor-alpha and interleukin-6 were significantly higher in coronary sinus blood than in arterial blood after aortic declamping. Tumor necrosis factor-alpha and interleukin-6 levels were also higher in mixed venous blood than in arterial blood within 1 hour after declamping. There were no significant differences among the three sampling sites with respect to interleukin-8 and interleukin-10 levels. In one patient who had postoperative myocardial infarction, however, interleukin-8 levels were three times as high as in coronary sinus blood than in arterial blood. These data indicate that the myocardium is a major source of tumor necrosis factor-alpha and interleukin-6 in patients undergoing cardiopulmonary bypass. The lungs may consume rather than release proinflammatory cytokines in the early phase of reperfusion. The source under these conditions of the antünflammatory cytokine interleukin-10 remains to be determined.

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Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.

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