Abstract | BACKGROUND: Heart muscle primarily relies on adenosine triphosphate produced by oxidative phosphorylation and is highly vulnerable to anoxic insult. Although a number of strategies aimed at improving myopreservation are available, no effective means of preserving mitochondrial energetics under conditions of anoxic injury have been developed. Openers of mitochondrial adenosine triphosphate-sensitive potassium channels have emerged as powerful cardioprotective agents presumably capable of maintaining mitochondrial function under metabolic stress. Here, we evaluated the ability of a prototype mitochondrial adenosine triphosphate-sensitive potassium channel opener, diazoxide, to preserve oxidative phosphorylation in mitochondria subjected to anoxia and reoxygenation. METHODS: Mitochondria were isolated from rat hearts and subjected to 20 minutes of anoxia, followed by reoxygenation. Mitochondrial respiration and oxidative phosphorylation, as well as mitochondrial integrity, were assessed by means of ion-selective minielectrodes, high-performance liquid chromatography, fluorometry, and electron microscopy. RESULTS: CONCLUSIONS: The present study demonstrates that diazoxide diminishes anoxia-induced functional and structural deterioration of cardiac mitochondria. By protecting mitochondria and preserving myocardial energetics, diazoxide may be useful under conditions of reduced oxygen availability, including global surgical ischemia or storage of donor heart.
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Authors | C Ozcan, E L Holmuhamedov, A Jahangir, A Terzic |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 121
Issue 2
Pg. 298-306
(Feb 2001)
ISSN: 0022-5223 [Print] United States |
PMID | 11174735
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Potassium Channels
- Adenosine Diphosphate
- Adenosine Triphosphate
- Adenylate Kinase
- Diazoxide
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Topics |
- Adenosine Diphosphate
(administration & dosage, metabolism)
- Adenosine Triphosphate
(biosynthesis)
- Adenylate Kinase
(metabolism)
- Animals
- Cell Hypoxia
(drug effects, physiology)
- Diazoxide
(pharmacology)
- Microscopy, Electron
- Mitochondria, Heart
(drug effects, metabolism)
- Oxidative Phosphorylation
(drug effects)
- Oxygen Consumption
- Potassium Channels
(drug effects)
- Rats
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