[Protective effect of mitochondrial ATP-sensitive potassium channel opener on rat heart during hypothermic preservation].
To investigate whether the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during hypothermic preservation of the rat heart.



The Langendorff model of isolated rat heart was used. After equilibrium, the hearts were stored in Celsior cardioplegia solution at 4 degree with or without supplement of diazoxide for 3 or 8 h followed by 60 minutes reperfusion. The recovery of cardiac contractile function, myocardial enzyme leakage in the coronary effluent, and myocardial water content were determined. The myocardial ultrastructure was also observed.



(1) Treatment of diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes, lactate dehydrogenase (LDH) and creatine kinase (CK), at the 2nd and 4th minute of reperfusion of rat heart after hypothermic preservation for 3 h. (2) After hypothermic preservation for 8 h, diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes (LDH, CK and glutamic oxalic transaminase) during reperfusion. Moreover, left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution. (3) Diazoxide significantly decreased the water content of myocardium and increased coronary flow of the hearts compared with those in control after hypothermic preservation for 8 h. (4) Impairment of myocardial ultrastructure after 8 h hypothermic preservation was alleviated in hearts treated with 30 mol/L diazoxide. (5) The cardiac effects of 30 mol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate (100 micromol/L).



Diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during hypothermic heart preservation via opening of mitochondrial K(ATP) channel.
Guo
Wei
W
Department of Physiology, College of Medicine, Zhejiang University, Hangzhou 310031, China.
Shen
Yue-liang
YL
Chen
Ying-ying
YY
Hu
Zhi-bin
ZB
Yan
Zhi-kun
ZK
Xia
Qiang
Q
D000818:Animals; D002314:Cardioplegic Solutions; D015925:Cryopreservation; D003981:Diazoxide / Q000494:pharmacology*; D006321:Heart; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002314:Cardioplegic Solutions; D019188:Organ Preservation Solutions; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D003981:Diazoxide