The effects of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery.

Abstract

Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may contribute to prolongation of systemic inflammation after cardiopulmonary bypass. Preoperative administration of glucocorticoids has been used ostensibly to attenuate the systemic inflammation associated with cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic signal transduction. Randomized control study. Medical school and affiliated tertiary care hospital. Thirteen patients undergoing coronary artery bypass grafting. Patients were randomly assigned to the control group (n = 7) or to receive 1 g of methylprednisolone sodium succinate on anesthetic induction (n = 6). Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, immediately postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6 hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte apoptosis was measured using propidium iodide-RNAase staining and flow cytometry. Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha, interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2) were measured. In all 13 patients, spontaneous and Fas-mediated PMN apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1. Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1 compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone administration did not modulate PMN apoptosis or immunocyte receptor expression; however, such treatment did decrease postoperative IL-6 secretion (P<.001) and increase postoperative IL-10 secretion (P<.001). The complications of major surgery include persistent inflammation, which can lead to multisystem organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute to this process. A single preoperative dose of glucocorticoids did not effect PMN apoptosis or receptor phenotype.