title: Mini Bypass and Proinflammatory Leukocyte Activation: A Randomized Controlled Trial.
abstract: BACKGROUND
  Coronary artery bypass grafting (CABG) with conventional cardiopulmonary bypass (CPB) induces systemic inflammation. Miniaturized CPB may attenuate systemic inflammatory activation. The intracellular signaling pathways promoting inflammation in cardiac operations and the relative effects of CPB on these processes are uncertain. In this study, induction of reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK) within leukocytes, and leukocyte accumulation in cantharidin-induced blisters was compared in patients exposed to miniaturized CPB (mCPB) and those who underwent conventional CPB (cCPB).
  
  
  METHODS
  Patients undergoing CABG were randomized to receive either cCPB (n = 13) or mCPB (n = 13). Blood samples were collected preoperatively and 5 times after initiating CPB (up to 5 hours) and analyzed by flow cytometry for intracellular markers of activation (ROS, p38-MAPK, and NF-κB phosphorylation).
  
  
  RESULTS
  ROS in lymphocytes were elevated in cCPB compared with mCPB (p < 0.01), whereas ROS in granulocytes and monocytes were similar between groups. After initiation of CPB, p38-MAPK was higher in patients receiving cCPB compared with those receiving mCPB (p < 0.05). NF-κB phosphorylation in leukocyte subsets was similar in patients exposed to cCPB and those exposed to mCPB. Leukocyte accumulation in cantharidin-induced blisters, white cell counts, and serum C-reactive protein (CRP) was enhanced in response to cardiac operations, but no differences were observed between mCPB and cCPB groups. Postoperative serum creatinine levels were reduced in the mCPB group compared with the cCPB group (p < 0.05).
  
  
  CONCLUSIONS
  Both p38-MAPK activation and ROS were attenuated with the use of mCPB compared with cCPB, providing a potential mechanism for reduced inflammation in association with CPB miniaturization.
authors.affiliation: Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Bao A V
authors.initials: BA
authors.lastname: Nguyen
authors.affiliation: Department of Cardiothoracic Surgery, Imperial College London, London, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fiorentino
authors.affiliation: Bristol Heart Institute and Clinical Trials & Evaluation Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Barnaby C
authors.initials: BC
authors.lastname: Reeves
authors.affiliation: Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Kamran
authors.initials: K
authors.lastname: Baig
authors.affiliation: Department of Cardiothoracic Surgery, Imperial College London, London, United Kingdom.
authors.forename: Thanos
authors.initials: T
authors.lastname: Athanasiou
authors.affiliation: Department of Cardiothoracic Surgery, Imperial College London, London, United Kingdom.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Dorian O
authors.initials: DO
authors.lastname: Haskard
authors.affiliation: Department of Cardiothoracic Surgery, Imperial College London, London, United Kingdom; Bristol Heart Institute and Clinical Trials & Evaluation Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom. Electronic address: paul.evans@sheffield.ac.uk.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Evans
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D002465:Cell Movement / Q000502:physiology; D016001:Confidence Intervals; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D023921:Coronary Stenosis / Q000097:blood / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008904:Miniaturization / Q000379:methods*; D016328:NF-kappa B / Q000097:blood*; D061646:Operative Time; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000097:blood; D018570:Risk Assessment; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood*
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases