Somatostatin analogue mimics acute ischemic preconditioning in a rat model of myocardial infarction.
We tested the hypothesis that octreotide, a somatostatin analogue, can mimic ischemic preconditioning (PC) to provide cardioprotection against myocardial infarction. An ischemia-reperfusion model of adult Wistar rats was used. Infarct size was expressed as a percentage of the area at risk under different treatment protocols. Octreotide PC (35 microg/Kg 20 minutes before ischemia-reperfusion) significantly decreased infarct size (18 +/- 4%) versus control (60 +/- 7%). The somatostatin receptor antagonist cyclo-somatostatin (0.5 mg/Kg) could blunt the above cardioprotection. Administration of either chelerythrine (a protein kinase C inhibitor, 2 mg/Kg) or genistein (a tyrosine kinase inhibitor, 5 mg/Kg) could also block octreotide PC (54 +/- 7% and 58 +/- 6%, respectively). Pretreatment with the mitochondrial ATP-sensitive potassium channel antagonist 5-hydroxydecanoic acid (5-HD) and the sarcolemmal ATP-sensitive potassium channel antagonist glibenclamide could abolish the effects of octreotide PC (54 +/- 6% and 52 +/- 6%). Chelerythrine, however, had no effect on octreotide PC. In conclusion, the present study demonstrates that octreotide can mimic ischemic PC to reduce infarct size. Acute effects of octreotide PC involve the activation of protein kinase C, tyrosine kinase C, and mitochondrial ATP-sensitive potassium channels, but not systemic IGF-I activation.
Wang
Tzong-Luen
TL
Department of Emergency Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. M002183@ms.skh.org.tw
Huang
Yu-Hui
YH
Chang
Hang
H
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015282:Octreotide / Q000031:analogs & derivatives / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
D013004:Somatostatin; D015282:Octreotide