Abstract | BACKGROUND: Mitochondrial changes that characterize the heart after anesthetic preconditioning (APC) or the mechanisms by which mitochondrial triggering factors lead to protection are unknown. This study hypothesized that generation of reactive oxygen species (ROS) during APC is required to initiate the mitochondrial protective effects, and that APC leads to improved mitochondrial electron transport chain function and cardiac function during reperfusion. METHODS: RESULTS: The APC improved cardiac function and reduced infarction. Tiron or MnTBAP abrogated the protection afforded by APC. Mitochondrial ATP synthesis was decreased by 70 +/- 3% after IR alone, by only 7 +/- 3% after APC, by 69 +/- 2% after APC+TIR, and by 71 +/- 3% after APC + TBAP. Mitochondrial ROS formation (DCF) increased by 48 +/- 3% after IR alone, by 0 +/- 2% after APC, by 43 +/- 4% after APC + TIR, and by 46 +/- 3% after APC + TBAP. ROS generation (DHE) was increased in I/R group at 5 and 120 min reperfusion. This was attenuated by APC but this protective effect was abrogated in APC + TIR and APC + TBAP groups. CONCLUSIONS: The results indicate that ROS are central both in triggering and mediating APC, and that the mitochondrion is the target for these changes.
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Authors | Enis Novalija, Leo G Kevin, Janis T Eells, Michele M Henry, David F Stowe |
Journal | Anesthesiology
(Anesthesiology)
Vol. 98
Issue 5
Pg. 1155-63
(May 2003)
ISSN: 0003-3022 [Print] United States |
PMID | 12717137
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Reactive Oxygen Species
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(metabolism)
- Animals
- Cell Fractionation
- Coronary Circulation
(physiology)
- Guinea Pigs
- Heart
(drug effects, physiology, physiopathology)
- In Vitro Techniques
- Ischemic Preconditioning, Myocardial
(methods)
- Mitochondria, Heart
(metabolism, ultrastructure)
- Models, Animal
- Myocardial Reperfusion
- Oxidation-Reduction
- Reactive Oxygen Species
(metabolism)
- Time Factors
- Ventricular Function, Left
(physiology)
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