Abstract | PURPOSE: METHODS: Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts. RESULTS:
Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0% of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4%; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1% (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane. CONCLUSIONS: Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.
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Authors | Yasuo M Tsutsumi, Rie Tsutsumi, Yousuke T Horikawa, Yoko Sakai, Eisuke Hamaguchi, Hiroshi Kitahata, Asuka Kasai, Noriko Kambe, Katsuya Tanaka |
Journal | Journal of anesthesia
(J Anesth)
Vol. 28
Issue 5
Pg. 733-9
(Oct 2014)
ISSN: 1438-8359 [Electronic] Japan |
PMID | 24633659
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anesthetics, Inhalation
- Caveolin 3
- Diterpenes
- Isoflurane
- geranylgeranylacetone
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Topics |
- Anesthetics, Inhalation
(administration & dosage, pharmacology)
- Animals
- Caveolae
(metabolism)
- Caveolin 3
(genetics, metabolism)
- Diterpenes
(administration & dosage, pharmacology)
- Drug Synergism
- Isoflurane
(administration & dosage, pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myocardial Infarction
(prevention & control)
- Myocardial Reperfusion Injury
(drug therapy)
- Myocytes, Cardiac
(drug effects, metabolism)
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