Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting

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.