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Anesth Analg 2008; 107:755-761
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31817f0e61
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CARDIOVASCULAR ANESTHESIOLOGY

Low-Dose Sevoflurane Inhalation Enhances Late Cardioprotection from the Anti-Ulcer Drug Geranylgeranylacetone

Hiroshi Kitahata, MD*, Junpei Nozaki, MD{dagger}, Shinji Kawahito, MD*, Takehito Tomino, BS*, and Shuzo Oshita, MD*

From the *Department of Anesthesiology, The University of Tokushima Graduate School, Institute of Health Biosciences, Tokushima, Japan; and {dagger}Department of Anesthesiology, Naruto Hospital, Tokushima.

Address correspondence and reprint requests to Hiroshi Kitahata, MD, PhD, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Address e-mail to hiroshi{at}clin.med.tokushima-u.ac.jp.

Abstract

BACKGROUND: We investigated in rabbits whether sevoflurane enhances late cardioprotection induced by geranylgeranylacetone (GGA), a gastric antiulcer drug.

METHODS: S(+)-ketamine and xylazine-anesthetized rabbits were assigned to one of seven experimental groups: a control (vehicle only) group, a GGA group, a sevoflurane group, a GGA+sevoflurane group, a sodium 5-hydroxydecanoate (5HD) group, a GGA + 5HD group, and a heat stress group. All rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were pretreated with IV vehicle, GGA (10 mg/kg), or heat stress (42°C for 15 min) 24 h before coronary occlusion. Sevoflurane (0.5 minimum alveolar concentration) or 5HD (5 mg/kg) were administered before myocardial ischemia. Myocardial infarct size and the area at risk for ischemia were measured, and heat shock protein (Hsp) 70 levels in each experimental group were determined.

RESULTS: Compared with vehicle only, GGA significantly reduced the size of myocardial infarction in relation to the area at risk (39 ± 10% vs 59 ± 9%, P < 0.02). Sevoflurane enhanced the GGA-induced cardioprotection (23 ± 17%, P < 0.05 vs GGA). The cardioprotective effect of GGA was abolished by administration of 5HD (56 ± 15%, P < 0.01). GGA enhanced Hsp 70 expression compared with that in the control group (0.69 ± 0.15 vs 0.36 ± 0.05, P < 0.02). Administration of GGA with sevoflurane resulted in the same level of Hsp 70 expression as GGA (0.69 ± 0.16, P > 0.98).

CONCLUSIONS: GGA appears to reduce myocardial infarct size in association with increased Hsp 70 expression. Sevoflurane enhances the GGA-induced cardioprotective effect.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.