Complement activation during cardiopulmonary bypass: quantitative study of effects of methylprednisolone and pulsatile flow.

Abstract

Forty four patients undergoing open heart surgery were divided into three groups. Group 1 (17 patients) underwent routine anaesthesia and surgery; group 2 (17 patients) received two doses of methylprednisolone (30 mg/kg), one during induction of anaesthesia and the other immediately before induction of cardiopulmonary bypass; and group 3 (10 patients) received pulsatile flow while undergoing pulsatile perfusion by the heart-lung machine. A modification of the previously described technique was used to detect and measure complement activation in plasma before and during the bypass period using crossed immunoelectrophoresis.About 45% of all patients showed measurable complement activation (>455%) during cardiopulmonary by-

Early- and Late-Phase Activation of Complement Evaluated by Plasma Levels of C3d,g and the Terminal Complement Complex

“…Acute in vivo activation of complement, induced by exposure to foreign surfaces dur ing extracorporeal circulation, has been de scribed earlier [28][29][30], C3 conversion during an anaphylactoid reaction has also been ex amined [31], and the half-life for the C3d split products was found there to be 4 h, as compared to 3 h found in the present study. The TCC in plasma seems to have a half-life which is slightly shorter than 1 h after acute in vivo activation.…”

Angiotensin-converting enzyme activity in serum and bronchoalveolar lavage fluid after damage to the alveolo-capillary barrier in the human lung

“…These differences can be explained by decreased degree of leukosequestration and decreased formation of microaggregates of PMN, by altered neutrophil chemotactic responses, altered neutrophil degranulation and inactivation or possibly by increased release of PMN out of the bone marrow [15,18]. Confirming other studies, methylprednisolone did not alter complement activation measured by consumption of C3 and C4 or production of C3d [19,20]. The values of serial serum ACE level determinations during cardiac surgery were not influenced by methylprednisolone.…”

Vasomotor dysfunction after cardiac surgery

“…), to the rarity and lack of sensitivity of adverse clinical outcomes, to the large potential for confounding biological noises such as baseline endothelial function and immunologic response in patients, and to the difficulty in a priori obtaining a proper treatment effect estimate in order to perform an adequate sample size calculation prior to launching these small trials. The clinical use of glucocorticosteroids on CPB constitutes one example of disappointing clinical results, since these agents, despite their theoretical role in blocking the effects of inflammatory cytokines and the expression of iNOS and COX-2, have repeatedly not resulted in appreciable clinical benefit [128,129], with the possible exception of decreased creatine kinase release and a reduction in the incidence of postoperative atrial fibrillation in two recent double-blind randomized controlled trials [130] (Rubens FD et al; in press). Also controversial has been the role of inhibiting neutrophil infiltration with a monoclonal antibody to C5a, which experimentally results in improved endothelial-dependent relaxation but no demonstrable benefit on myocardial, pulmonary, or mesenteric functional recovery [31,131,132], until one clinical trial demonstrated a dose-dependent inhibition of the generation of complement byproducts, a reduction in leukocyte activation, a 40% reduction in creatine kinase-MB release, a 80% reduction in new cognitive deficits, and a significant reduction in postoperative blood loss [133].…”