Abstract | BACKGROUND: METHODS: In vivo or Langendorff-perfused mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in the presence and absence of postconditioning produced with isoflurane 5 min before and 3 min after reperfusion. Ca+-induced mitochondrial permeability transition (MPT) pore opening was assessed in isolated mitochondria. Echocardiography was used to evaluate ventricular function. RESULTS: Postconditioning with 0.5, 1.0, and 1.5 minimum alveolar concentrations of isoflurane decreased infarct size from 56 +/- 10% (n = 10) in control to 48 +/- 10%, 41 +/- 8% (n = 8, P < 0.05), and 38 +/- 10% (n = 8, P < 0.05), respectively, and improved cardiac function in wild-type mice. Improvement in cardiac function by IsoPC was blocked by N-nitro- L-arginine methyl ester (a nonselective nitric oxide synthase inhibitor) administered either before ischemia or at the onset of reperfusion. Mitochondria isolated from postconditioned hearts required significantly higher in vitro Ca+ loading than did controls (78 +/- 29 microm vs. 40 +/- 25 microm CaCl2 per milligram of protein, n = 10, P < 0.05) to open the MPT pore. Hearts from eNOS mice displayed no marked differences in infarct size, cardiac function, and sensitivity of MPT pore to Ca+, compared with wild-type hearts. However, IsoPC failed to alter infarct size, cardiac function, or the amount of Ca+ necessary to open the MPT pore in mitochondria isolated from the eNOS hearts compared with control hearts. CONCLUSIONS: IsoPC protects mouse hearts from reperfusion injury by preventing MPT pore opening in an eNOS-dependent manner. Nitric oxide functions as both a trigger and a mediator of cardioprotection produced by IsoPC.
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Authors | Zhi-Dong Ge, Danijel Pravdic, Martin Bienengraeber, Phillip F Pratt Jr, John A Auchampach, Garrett J Gross, Judy R Kersten, David C Warltier |
Journal | Anesthesiology
(Anesthesiology)
Vol. 112
Issue 1
Pg. 73-85
(Jan 2010)
ISSN: 1528-1175 [Electronic] United States |
PMID | 19996950
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Anesthetics, Inhalation
- Cardiotonic Agents
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- Nitric Oxide
- Isoflurane
- Nitric Oxide Synthase Type III
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Topics |
- Anesthetics, Inhalation
(pharmacology)
- Animals
- Cardiotonic Agents
- Echocardiography
- Heart Rate
(drug effects)
- In Vitro Techniques
- Isoflurane
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mitochondria, Heart
(drug effects)
- Mitochondrial Membrane Transport Proteins
(drug effects)
- Mitochondrial Permeability Transition Pore
- Myocardial Reperfusion Injury
(prevention & control)
- Nitric Oxide
(physiology)
- Nitric Oxide Synthase Type III
(genetics, physiology)
- Permeability
(drug effects)
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