title: Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial.
abstract: OBJECTIVE
  The efficacy of myocardial conditioning strategies is compromised in patients with advanced age, diabetes, or low ejection fraction. We conducted a single-centre parallel-arm blinded randomized-controlled trial to determine whether propofol provides perioperative myocardial protection.
  
  
  METHODS
  Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass (CPB) with blood cardioplegia. The participants were stratified by diabetic status and left ventricular ejection fraction and randomly assigned to receive either an elevated dose of propofol -previously associated with experimental cardioprotection- or an isoflurane preconditioning regime. The primary endpoint was the coronary sinus (CS) concentration of 15-F2t-isoprostane (isoP). Secondary endpoints included in-hospital low cardiac output syndrome (LCOS) and major adverse cardiac events, 12- and 24-hr CS cardiac troponin I (cTnI) release, and myocardial B-cell lymphoma 2 (Bcl-2) protein expression.
  
  
  RESULTS
  Data were analyzed from 125 of 137 randomized participants. Participants receiving propofol experienced a greater mean (SD) increase from baseline in CS 15-F2t-isoP levels compared with those receiving isoflurane [26.9 (10.9) pg·mL(-1) vs 12.1 (10.4) pg·mL(-1), respectively; mean difference, 14.8; 95% confidence interval (CI), 11.0 to 18.6; P < 0.001] but a decreased incidence of LCOS (20.9% vs 57.1%, respectively; relative risk [RR],0.37; 95% CI, 0.22 to 0.62; P < 0.001). The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus (DM2) (P = 0.382) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup (17.9% vs 70.3%, respectively; RR, 0.26; 95% CI, 0.13 to 0.52; P < 0.001). Propofol was associated with an increase in myocardial Bcl-2 protein expression (P = 0.005), a lower incidence of a CS cTnI threshold for myocardial infarction (P = 0.014), and fewer heart failure events (P < 0.001).
  
  
  CONCLUSIONS
  Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest. The study is registered at www.clinicaltrials.gov (NCT00734383) and www.controlled-trials.com (ISRCTN70879185).
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, Canada. david.ansley@vch.ca.|Department of Anesthesiology and Perioperative Care, Vancouver General Hospital, Vancouver, BC, Canada. david.ansley@vch.ca.|Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Room 3300, 3rd Floor JPP, 910 West 10th Ave, Vancouver, BC, V5Z 1M9, Canada. david.ansley@vch.ca.
authors.forename: David M
authors.initials: DM
authors.lastname: Ansley
authors.affiliation: Heart Institute - Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Koen
authors.initials: K
authors.lastname: Raedschelders
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, Canada.|Department of Anesthesiology and Perioperative Care, Vancouver General Hospital, Vancouver, BC, Canada.|Center for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Baohua
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Surgery (Division of Cardiac Surgery), The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Cook
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: David D Y
authors.initials: DD
authors.lastname: Chen
mesh_terms: D000368:Aged; D018686:Anesthetics, Intravenous / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000517:prevention & control*; D001026:Coronary Artery Bypass; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D007530:Isoflurane / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D017382:Reactive Oxygen Species; D007530:Isoflurane; D015742:Propofol