Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass.
BACKGROUND
Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes.


METHODS
In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined.


RESULTS
The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need.


CONCLUSIONS
This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent.
Rubens
Fraser D
FD
Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada. frubens@ottawaheart.ca
Nathan
Howard
H
Labow
Rosalind
R
Williams
Kathryn S
KS
Wozny
Denise
D
Karsh
Jacob
J
Ruel
Marc
M
Mesana
Thierry
T
D015415:Biomarkers / Q000378:metabolism; D001790:Blood Physiological Phenomena / Q000187:drug effects*; D001920:Bradykinin / Q000096:biosynthesis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000517:prevention & control; D010196:Pancreatic Elastase / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*
D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007378:Interleukins; D011108:Polymers; D010196:Pancreatic Elastase; D001920:Bradykinin; D008775:Methylprednisolone