Activation of Mitochondrial ATP-Sensitive Potassium Channel Contributes to Protective Effect in Prolonged Myocardial Preservation.
To find a better strategy for effective donor organ preservation, here we used a model of long-term hypothermia preservation of rat hearts to investigate the cardioprotective effects of diazoxide, a selective opener of mitochondrial ATP-sensitive potassium channel (mitoKATP). Cardiac function was impaired by 8-hour ischemic preservation following 30 minutes of reperfusion. Treatment with diazoxide significantly attenuated the decline of myocardial contractility, and decreased the lactate dehydrogenase leakage and myocardial edema. Diazoxide also prevented the loss of activity of mitochondrial superoxide dismutases and sarcolemmal Na+/K+ATPase during ischemia or reperfusion period, respectively. These effects of diazoxide could be abolished by a selective mitoKATpblocker 5-hydroxydecanoate. The results suggest that diazoxide, as a supplementation in cardioplegic solution, could enhance myocardial protection by opening mitoKATpchannel, and better maintenance of mitochondrial anti-oxidative enzyme.
Guo
Wei
W
Dept. of Phys., Zhejiang Univ. Sch. of Med., Hangzhou.
Chen
Nan
N
Chen
Yingying
Y
Xia
Qiang
Q
Shen
Yueliang
Y