dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts

Abstract

To investigate the role of high concentrations of dl-3-hydroxybutyrate (DL-3-HB) in preventing heart damage after prolonged fasting, infarct size and the incidence of apoptosis caused by ischemia-reperfusion were determined in four groups of Wistar rats. Fed rats (±DL-3-HB group) and fasted rats (±DL-3-HB group) were subjected to 30 min of left coronary artery occlusion and 120 min of reperfusion. DL-3-HB was administered intravenously 60 min before the coronary artery occlusion. Infarct size, defined by triphenylyetrazolium chloride (TTC) staining, was reduced from 72 ± 3% (fed group), 75 ± 5% (fed + DL-3-HB group), and 70 ± 5% (fasting group), respectively, to 26 ± 4% ( P < 0.01 vs. fasting + DL-3-HB group). Apoptosis, as defined by single-stranded DNA staining, was significantly reduced in the subendocardial region in the fasting + DL-3-HB group (9 ± 2%) compared with the other groups (39 ± 6% in the fed group, 37 ± 5% in the fed + DL-3-HB group, and 34 ± 3% in the fasting group; P < 0.01). In addition, levels of ATP in the fasting + DL-3-HB group were significantly higher compared with other groups after 30 min of ischemia and 120 min of reperfusion ( P < 0.01). In conclusion, the present study demonstrates that high concentrations of DL-3-HB reduces myocardial infarction size and apoptosis induced by ischemia-reperfusion, possibly by providing increased energy substrate to the fasted rat myocardium.