Low-dose sevoflurane inhalation enhances late cardioprotection from the anti-ulcer drug geranylgeranylcacetone

Low-dose sevoflurane inhalation enhances late cardioprotection from the anti-ulcer drug geranylgeranylcacetone
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DOI:
10.1213/ane.0b013e31817f0e61
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发表时间:
2008-09-01
影响因子:
5.7
通讯作者:
Oshita, Shuzo
Oshita, Shuzo
中科院分区:
医学2区
文献类型:
--
作者:
Kitahata, Hiroshi;Nozaki, Junpei;Oshita, Shuzo

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方法:将S(+)-氯胺酮和赛拉津麻醉的兔分为7组:对照组(仅限溶剂)、GGA组、七氟醚组、GGA+七氟醚组、GGA+5HD组、GGA+5HD组和热应激组。所有兔均行冠状动脉结扎30min,再灌注3h。在冠脉阻断前24 h,静脉注射赋形剂、GGA(10 mg/kg)或热应激(42℃,15分钟)。心肌缺血前给予七氟醚(最低肺泡浓度0.5)或5HD(5 mg/kg)。结果:与空白对照组相比,GGA组大鼠心肌梗死面积明显缩小(39+/-10%比59+/-9%,P<0.02)。七氟醚可增强GGA诱导的心肌保护作用(23+/-17%,P<0.05 vs G(,A))。GGA的心脏保护作用可被5HD取消(56+/-15%,P<0.01)。GGA组HSP70表达高于对照组(0.69+/-0.15 vs 0.36+/-0.05,P<0.02)。给予GGA和七氟醚后,HSP70的表达水平与GGA相同(0.69+/-0.16,P>0.98)。结论:GGA可减少心肌梗死面积,增加HSP70的表达。七氟醚可增强GGA诱导的心脏保护作用。
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 G(,A). 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.