Low-dose sevoflurane inhalation enhances late cardioprotection from the anti-ulcer drug geranylgeranylacetone.
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 degrees 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.
Kitahata
Hiroshi
H
Department of Anesthesiology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. hiroshi@clin.med.tokushima-u.ac.jp
Nozaki
Junpei
J
Kawahito
Shinji
S
Tomino
Takehito
T
Oshita
Shuzo
S
D000280:Administration, Inhalation; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D003331:Coronary Vessels / Q000473:pathology; D004224:Diterpenes / Q000627:therapeutic use*; D004357:Drug Synergism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D000077149:Sevoflurane; D013997:Time Factors
D000897:Anti-Ulcer Agents; D002316:Cardiotonic Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D008738:Methyl Ethers; D000077149:Sevoflurane; D011493:Protein Kinase C; C031049:geranylgeranylacetone