dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts.
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.
Zou
Zhitian
Z
Department of Surgery II, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Sasaguri
Shiro
S
Rajesh
Katare Gopalrao
KG
Suzuki
Ryoko
R
D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000494:pharmacology*; D000090:Acetoacetates / Q000097:blood; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose; D001794:Blood Pressure; D001835:Body Weight; D003327:Coronary Disease / Q000188:drug therapy*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006339:Heart Rate; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000090:Acetoacetates; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019344:Lactic Acid; C016635:acetoacetic acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D020155:3-Hydroxybutyric Acid