Comparative antiapoptotic effects of KB-R7943 and ischemic postconditioning during myocardial ischemia reperfusion.
We examined whether KB-R7943 reduced infarct size by attenuating apoptosis during reperfusion and also compared antiapoptotic effects of KB-R7943 and IPost. For this purpose, isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Ischemic postconditioning (IPost) (n = 15; three cycles of 10-s reperfusion/10-s ischemia or three cycles of 30-s reperfusion/30-s ischemia) and KB-R7943 (n = 15; 1 μM KB-R at the onset of reperfusion or before ischemia) were compared with controls (n = 12; ischemia-reperfusion only). Myocardial injury was determined by TTC staining, TUNEL assay and caspase-3 activity. AKT and eNOS phosphorylation were measured by immunoblotting. We found that IPost (10 s), Pre KB-R, and Reperf KB-R reduced infarct size (29 ± 4.1, 35 ± 5.0, 28.6 ± 3.4 %, respectively, vs. controls 46 ± 8.7 %; P < 0.05) and attenuated cell apoptosis (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P < 0.01). Moreover, IPost (10 s), Pre KB-R and Reperf KB-R significantly decreased caspase-3 activation caused by myocardial ischemia-reperfusion. However, IPost (30 s) did not show any effect on necrosis and apoptosis. Akt, eNOS phosphorylation, at 30 min of reperfusion/IPost-10 s was significantly higher than other groups. In conclusion, KB-R7943 was as effective as IPost in reducing necrosis and inhibiting apoptosis and it might be an ideal pharmacological agent to provide a more amenable approach to cardioprotection.
Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
Yongkui
Y
Ren
Yunfei
Y
Cai
Dalin
D
Jia
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D057775:Ischemic Postconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009336:Necrosis / Q000503:physiopathology / Q000517:prevention & control; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D013890:Thiourea