Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice

To the Editor:

Recently, Suzuki et al reported that attenuation of myocardial stunning by diazoxide in mice was mediated through activation of sarcolemmal rather than mitochondrial K⁺_ATP channels. Although the authors used an elegant approach by combining both pharmacological tools (utilizing the mitochondrial K⁺_ATP-channel inhibitor 5-hydroxydecanoate and the sarcolemmal K⁺_ATP channel inhibitor HMR-1098) and molecular tools (sarcolemmal K⁺_ATP channel [Kir6.2]-deficient mice), interpretation of the results is difficult.

Thus, the authors claim to have investigated the protective effects of pretreatment with diazoxide against myocardial stunning, produced by 20 minutes of no-flow global ischemia in isolated buffer-perfused hearts. However, stunning is defined as reversible myocardial dysfunction that persists after a brief period of ischemia despite full reperfusion. In isolated buffer-perfused rodent hearts, 20 minutes of ischemia already results in significant cardiac necrosis. [...]