ArticleThe Annals of thoracic surgery2002
Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery.
Article in The Annals of thoracic surgery, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 37 citations in OpenAlex.
- DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion.Biomedicines · 2021Article
- A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy.JACC. Basic to translational science · 2019Article
- Protective role of STVNa in myocardial ischemia reperfusion injury by inhibiting mitochondrial fission.Oncotarget · 2018Article
- Transit and integration of extracellular mitochondria in human heart cells.Scientific reports · 2017Article
- Article
- Variable effects of the mitoK(ATP) channel modulators diazoxide and 5-HD in ATP-depleted renal epithelial cells.Molecular and cellular biochemistry · 2010Article
- Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart.Physiological genomics · 2009Article
- Injection of isolated mitochondria during early reperfusion for cardioprotection.American journal of physiology. Heart and circulatory physiology · 2009Article
- Cardioplegia and diazoxide modulate STAT3 activation and DNA binding.The Annals of thoracic surgery · 2007Article
- Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion.The Annals of thoracic surgery · 2006Article
- Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide.The Annals of thoracic surgery · 2006Article
- Role of proteases in the pathophysiology of cardiac disease.Molecular and cellular biochemistry · 2004Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRecently, we have shown that the selective opening of mitochondrial ATP-sensitive potassium channels with diazoxide significantly decreases myocardial injury. The purpose of this study was to determine the effects of diazoxide on apoptosis and the mechanisms modulating apoptosis and myocardial injury in a blood-perfused model of acute myocardial infarction.
methodsPigs (32 to 42 kg) undergoing total cardiopulmonary bypass underwent left anterior descending coronary artery occlusion for 30 minutes. The aorta was cross-clamped and magnesium-supplemented potassium cold-blood cardioplegia (DSA; n = 6) or magnesium-supplemented potassium cardioplegia containing 50 micromol/L diazoxide (DZX; n = 6) was administered, followed by 30 minutes of global ischemia and 120 minutes of reperfusion. Left ventricular tissue samples from DSA and DZX hearts were obtained after reperfusion. Apoptosis was determined by TUNEL, caspase-3 and PARP cleavage, and caspase-3 activity. Bax and bcl-2 levels were determined and tissue morphology was examined by light and transmission electron microscopy.
resultsApoptosis, as estimated by TUNEL-positive nuclei/3,000 myocardial cells, was 120.3 +/- 48.8 in DSA hearts and was significantly decreased to 21.4 +/- 5.3 in DZX hearts (p < 0.05 vs control). Caspase-3 and poly-ADP-ribose polymerase cleavage and pro-apoptotic bax protein levels were significantly decreased with diazoxide (p < 0.05 vs DSA). Light and transmission electron microscopy indicated severe disruption of tissue with capillary dilatation, mitochondrial cristae damage, and evidence of increased presence of mitochondrial granules in DSA as compared with DZX hearts.
conclusionsThe addition of diazoxide (50 micromol/L) to cardioplegia significantly decreases regional myocardial apoptosis and mitochondrial damage, and provides an additional modality for achieving myocardial protection.
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