不同方式七氟醚缺血处理对大鼠离体心脏缺血 - 再灌注损伤的保护作用的比较

目的比较七氟醚缺血预处理、七氟醚缺血后处理及七氟醚缺血预处理联合七氟醚缺血后处理3种方式对大鼠离体心脏缺血-再灌注损伤保护效果及相关机制方法大鼠心脏离体平衡期灌住10min后随机分为4组：对照（CTRL）组，全心缺血30min随后复灌120min，无其它干预；七氟醚缺血预处理（SpreC）组：以3％七氟醚行缺血预处理15min，洗出10min．后全心缺血30min复灌120min；七氟醚后处理（SpostC）组：全心缺血30min．随后复灌60min，复灌最初15min行3％七氟醚缺血后处理；SpreC＋SpostC组：联合使用SpreC和SpostC，比较组内不同时点及组间相同时点的血流动力学．所有实验组行组内不同时点和组间同时点的血流动力学比较及左室梗死面积比较。

Comparison of Cardio-protective Effects Induced by Different Modalities of Sevoflurane Conditioning in Isolated Rat Hearts Subjected to Ischemia-Reperfusion Injury

Objective It remains undetermined whether the combination of anesthetic preconditioning and anesthetic postconditioning could provide greater protection against myocardial ischemia-reperfusion injury than either anesthetic preconditioning or anesthetic postconditioning alone. The objectives of the current study were to compare the cardioprotective effects of sevoflurane preconditioning, sevoflurane postconditioning and sevoflurane preconditioning plus postconditioning, and to examine somc possible underlying mechanisms which might explain the relative efficacy of the three different modalities of scvoflurane conditioning. Methods After 10 rain of equilibration, isolated rat hearts were randomly assigned into one of the fbnr groups： CTRL group （30 rain of ischemia ~bllowed by 120 rain of reperfusion alone） served as non-treated control; SpreC group （3% sevoflurane preconditioning was administered for 15 rain followed by 10 rain of washout before ischemia）; SpostC group （3% sevoflurane postconditioning was administered during the first 15 rain of reperfusion after isehemia）; SpreC＋SpostC group （the protocols of SpreC and SpostC groups were combined）. Hemodynamics was compared within and between groups. Infarct size was determined at the end of 120 rain of reperfusion using triphenyltetrazolium chloride （TTC） staining. Lactate dehydrogenase （LDH） and creatine kinasc-MB （CK-MB） released from necroticmyocardium, were compared among groups. Time course of the two key pro-survival kinases, namely protein kinase B （PKB/Akt） and extracellular signal-regulated kinase 1/2 （ERK 1/2） activation in four groups, were determined by Western blotting analysis. Mitochondrial permeability transition pore （mPTP） status was compared by assaying myocardium nicotinamide adenine dinucleotide （NAD＋） content. Results When compared with unprotected CTRL ones, hearts in sevoflurane-treated groups （SpreC, SpostC and SpreC＋SpostC） showed significantly better functional recovery （improved LVDP, ＋dp/dt, dp/dt, CK HR and reduced LVEDP）, reduced myocardial infarct size, decreased LDH and CK-MB release （P〈0.05）. Comparison of the above-mentioned varibles among three sevoflurane-treated groups showed that, maximal cardioprotection was obtained in SpreC＋SpostC group （P〈0.05）, and no difference was found between SpreC and SpostC groups （P〉0.05）. Western blotting analysis revealed that CTRL hearts showed increased PKB/Akt and ERK-1/2 phosphorylation after ischemia-reperfusion when compared to the baseline values. Both SpreC and SpreC＋SpostC induced a biphasic response in PKB/Akt and ERK-I/2 phosphorylation during the preconditioning and reperfusion phases following ischemia. SpostC induced only one phase of enhanced PKB/Akt and ERK-I/2 phosphorylation, which occurred after sevoflurane postconditioning. And the effects on phosphorylation of both PKB/Akt and ERK-1/2 induced by SpreC and SpostC was found to be additive at 15 min and 120 rain of reperfusion. The CTRL hearts have the lowest myocardial NAD＋ content among all groups （P〈0.05）. While SpreC＋SpostC hearts retained higher contents of NAD＋ than either SpreC or SpostC ones （P〈0.05）, suggesting that the combination of sevoflurane preconditioning and postconditioning had also additive effects on inhibiting mPTP opening induced by ischemia-reperfhsion. Conclusions SpreC and SpostC wcre equally effective in protecting against MIRI, as manifested by functional recovery, infarct size and biomarkcrs reduction, kinasc activation and mPTP inhibition. The combination of SpreC and SpostC offered additive protection in all these above aspects