Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis

Abstract

The addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.

Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding

“…Surgical preparation (sternotomy, tracheotomy, cannulation) were performed as previously described [8,9]. General anesthesia was induced (3%) and maintained (1%) with sevoflurane (Ultane; Abbott Laboratories).…”

“…The DMSO was added as vehicle sham to DSA cardioplegia (final concentration less than 0.1%). At 15 minutes of global ischemia, an additional 5 mL/kg of DSA cardioplegia without diazoxide was readministered in both groups [8]. All hearts received topical hypothermia during global ischemia [8].…”

“…At 15 minutes of global ischemia, an additional 5 mL/kg of DSA cardioplegia without diazoxide was readministered in both groups [8]. All hearts received topical hypothermia during global ischemia [8]. After 30 minutes of hypothermic global ischemia, the cross clamp and the snare from the LAD were released, the ice packing was removed and the hearts were kept on total CPB for 120 minutes of reperfusion.…”

“…In previous studies, we have shown that magnesium supplemented potassium (DSA) cardioplegia significantly decreases apoptosis after ischemia [8,9]. We have also shown that the mitochondrial adenosine triphosphate (ATP)-sensitive potassium (mitoK ATP ) channels play an important role in the cardioprotection afforded by DSA cardioplegia and that the early or enhanced opening of the mitoK ATP channels with the addition of diazoxide to DSA cardioplegia (DSA+DZX) significantly decreases apoptosis as compared with DSA cardioplegia alone [8,9].…”

“…We have also shown that the mitochondrial adenosine triphosphate (ATP)-sensitive potassium (mitoK ATP ) channels play an important role in the cardioprotection afforded by DSA cardioplegia and that the early or enhanced opening of the mitoK ATP channels with the addition of diazoxide to DSA cardioplegia (DSA+DZX) significantly decreases apoptosis as compared with DSA cardioplegia alone [8,9]. In the present study, we investigate the effects of ischemia and reperfusion and DSA and DSA+DZX cardioplegia on STAT1 and STAT 3 phosphorylation and DNA binding by extending our previous studies in the in situ blood-perfused pig heart model of acute myocardial infarction [8,9].…”