Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: a double-blind randomized feasibility study of diazoxide-supplemented cardioplegia.

摘要: Objectives The study was designed to assess whether diazoxide-mediated cardioprotection might be used in human subjects during cardiac surgery. Methods Forty patients undergoing coronary artery bypass grafting were randomized receive intermittent warm blood antegrade cardioplegia supplemented with either diazoxide (100 μmol/L) or placebo (n = 20 each group). Mitochondria assessed before and after ischemia reperfusion myocardial biopsy specimens. Myocardial oxygen glucose lactic acid extraction ratios measured the first minutes of reperfusion. Hemodynamic data collected, troponin I, creatine kinase–MB, N-terminal prohormone brain natriuretic peptide levels measured. All outcomes analyzed by using mixed-effects modeling for repeated measures. Results No deaths, strokes, infarcts observed. Patients received, on average, 36.2 ± 1.2 mg 37.3 1.9 ( P .6). Diazoxide added prevented mitochondrial swelling (8899 474 vs 9273 688 pixels procedure, respectively; .6) compared that seen group (8474 163 11,357 759 pixels, .004). debt observed group. Glucose consumption production returned preischemic values faster following hemodynamic parameters differed between groups, respectively, postoperative period: index, 3.0 0.09 versus 2.6 L · min −1 m −2 .002); left work 2.81 0.07 2.31 kg/m 2 .03); ratio, 29.3% 1.1% 32.6% .02). Postoperative enzyme did not differ, but lower (120 27 192 29 pg/mL, .04). Conclusions Supplementing is safe improves protection surgery, possibly through its influence mitochondria.