title: Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting.
abstract: OBJECTIVE
  To investigate whether novel pharmacological preconditioning with diazoxide could protect the myocardial function and decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG).
  
  
  METHODS
  Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control group (n=20) and diazoxide (DZX) group (n=20). In the DZX group, 1.5 mg/kg diazoxide was infused intravenously within 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass (CPB). In the control group, a time-matched period of placebo infusion was given. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively.
  
  
  RESULTS
  There were no adverse effects related to diazoxide. Cardiac index (CI) increased postoperatively as compared with baseline. In the DZX group, the improvement of CI was better than that in the control group (p=0.001). Left and right ventricular stroke work indexes decreased postoperatively, and recovered much faster in the DZX group (p=0.027 and p=0.049, respectively). There were no statistically significant differences in the other hemodynamic parameters. The creatine kinase cardiac isoenzyme (CK-MB) was highest in both groups on the first postoperative day (control 28.8+/-23.8 and DZX 27.3+/-19.4, N.S.). The cumulative release of CK-MB postoperatively was lower in the DZX patients as compared with the controls, but the difference remained not significant (p=0.09).
  
  
  CONCLUSIONS
  Pharmacological preconditioning of the human heart with diazoxide is feasible; it confers additional myocardial protection beyond that provided by the cardioplegia alone by attenuating myocardial stunning after CABG operations.
authors.affiliation: Division of Cardiothoracic Surgery, Tampere University Hospital, Tampere, Finland.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Minxin
authors.initials: M
authors.lastname: Wei
authors.forename: Pekka
authors.initials: P
authors.lastname: Kuukasjärvi
authors.forename: Jari
authors.initials: J
authors.lastname: Laurikka
authors.forename: Otso
authors.initials: O
authors.lastname: Järvinen
authors.forename: Timo
authors.initials: T
authors.lastname: Rinne
authors.forename: Eva Liisa
authors.initials: EL
authors.lastname: Honkonen
authors.forename: Matti
authors.initials: M
authors.lastname: Tarkka
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D003981:Diazoxide / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D017682:Myocardial Stunning / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D011184:Postoperative Period; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D014665:Vasodilator Agents; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D003981:Diazoxide