Human cytokine responses to cardiac transplantation and coronary artery bypass grafting

Abstract

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.

Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis

“…Interestingly, this upregulation of CD163 may be linked to a prior surge in plasma IL-10 that we observed at 90 minutes after the onset of CPB (data not shown) and consistent with previous studies. 41,42 Also, we demonstrate a significant induction of intracellular HO-1 levels in circulating monocytes 24 to 48 hours after CPB surgery. Based on both the time course of this response and our in vitro findings, it is possible that this occurs secondary to CD163 upregulation and Hb:Hp complex scavenging.…”

Effects of Perfusion Temperature on Inflammatory Response and Outcome Following Cardiopulmonary Bypass

“…IL-6 concentrations have been shown to be much higher in patients undergoing heart transplantation, in which the duration of myocardial ischemia was much longer than in those undergoing coronary revascularization (16). There is evidence linking this cytokine to the pathogenesis of reperfusion injury, the post perfusion syndrome and the adult respiratory distress syndrome (17)(18)(19).…”

“…While all the studies mentioned above have provided some insight into the effects of normothermic bypass upon the inflammatory response, the practical significance with regard to end organ dysfunction still requires further evaluation. Of interest would be the effects of normothermic bypass on the systemic response in higher risk patients and those enduring long aortic cross clamp and cardiopulmonary bypass times (12,16,20). Also, normothermic CPB resulted in a shorter extracorporeal perfusion time and, postoperative course with a shorter extubation time, less bleeding and shorter ICU stay (21,22).…”

Study on the Relationship of APACHE III and Levels of Cytokines in Patients with Systemic Inflammatory Response Syndrome after Coronary Artery Bypass Grafting

“…The major pro-inflammatory cytokines involved are IL6, IL8, and TNF-a. 8,9) Researchers have proved that IL6 is responsible for induction of the synthesis of acute phase proteins and is the most important endogenous substance involved in inflammatory reactions and cytotoxity. Its continuous elevation has a close relation with cardiac dysfunction following surgery.…”