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A Double-blind Randomized Trial of Diazoxide Supplemented Cardioplegia
M. A. Deja, M. Malinowski, K. S. Golba, K. Widenka, W. Domaradzki, D. Szurlej, J. Biernat, M. Kajor, T. Lebda-Wyborny, S. Wos. Medical University of Silesia, Katowice, Poland,
OBJECTIVE To assess whether diazoxide added to cardioplegia improves myocardial protection in clinical settings.
METHODS. 40 patients undergoing CABG were randomized to receive intermittent warm-blood antegrade cardioplegia supplemented with diazoxide (100 µM) or placebo. Mitochondria size was compared in LV biopsies taken before AXC and before chest closure. Myocardial metabolism was studied sampling coronary sinus blood. The hemodynamic data were collected. The troponin I, CKMB and proNT-BNP was measured. All outcomes were analyzed using two-way repeated measure covariance (ANCOVA) analysis.
RESULTS No deaths, strokes, or MIs were observed. Patients received on average 36.2 ± 1.2mg of diazoxide and 37.3 ± 1.9mg of placebo (p=0.6). Mitochondria size increased from 8474 ± 163 pixels to 11357 ± 759 pixels (p = 0,004) in placebo group and did not change in diazoxide group: 8899 ± 474 vs 9273 ± 688 pixels (p = 0.6). Diazoxide decreased myocardial oxygen extraction ratio 45±1 vs 50±2% (p = 0.04), glucose extraction ratio 7±0.9 vs 10±1.0% (p=0.03), and lactate production -24±6 vs -55±14% (p=0.04) in reperfusion. The following hemodynamic parameters differed in post-op period : CI 3.0±0.09 vs. 2.7±0.09 l/min/m2 (p=0,02), LCW 5.5±0.2 vs 4.4±0.2 kgm (p = 0.001), LVSW 55.3±1.6 vs 50.2±1.6 gm/beat (p=0.04), DO2I 424±15 vs 375±14 ml/min/m2 (p = 0.03), O2ER 28±0.9 vs 31±0.9 % (p=0.02). Postoperative enzymes did not differ. ProNT-BNP was lower in diazoxide group 124±20 vs 182±21 pg/ml (p=0.05).
CONCLUSIONS Diazoxide improves myocardial metabolism in reperfusion, protects mitochondria from ischemia reperfusion injury and improves cardiac performance in postoperative period.
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