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Effects of Glucose Concentration on Propofol Cardioprotection against Myocardial Ischemia Reperfusion Injury in Isolated Rat Hearts

机译:葡萄糖浓度对异丙酚对离体大鼠心脏心肌缺血再灌注损伤的保护作用

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摘要

The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5.5 mM (LG) or 8 mM (G) in the absence or presence of propofol (5 μg/mL) or propofol plus trimetazidine (TMZ). Hearts were subjected to 35 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial infarct size (IS) and cardiac CK-MB were significantly higher in LG than in G group (P < 0.05), associated with reduced left ventricular developed pressure and increases in postischemic cardiac contracture. Cardiac 15-F2t-isoprostane was higher, accompanied with higher cardiac lipid transporter CD36 protein expression in LG. Propofol reduced IS, improved cardiac function, and reduced CD36 in G but not in LG. TMZ facilitated propofol cardioprotection in LG. Therefore, isolated heart with low glucose lost sensitivity to propofol treatment through enhancing FA oxidation and TMZ supplementation restored the sensitivity to propofol.
机译:麻醉性异丙酚可通过减少活性氧(ROS)来保护心肌免受缺血再灌注损伤(IRI)。但是,它对患者的心脏保护作用是不一致的。同样,最近有人质疑在心脏手术期间严格控制血糖的益处。我们推测低糖(LG)可能通过增强脂肪酸(FA)氧化并在IRI期间掩盖丙泊酚的心脏保护作用来促进ROS的形成。分离大鼠心脏并随机分配其在不存在或存在丙泊酚(5μg/ mL)或丙泊酚加曲美他嗪(TMZ)的情况下,用5.5 mM(LG)或8 mM(G)的葡萄糖灌注Krebs-Henseleit溶液。心脏经受35分钟的缺血,然后再灌注60分钟。 LG组的心肌梗死面积(IS)和心脏CK-MB显着高于G组(P <0.05),这与左心室发育压力降低和缺血后心脏挛缩增加有关。心脏中15-F2t-异前列腺素水平更高,并伴有较高的心脏脂质转运蛋白CD36蛋白在LG中的表达。丙泊酚可降低IS的IS,改善心脏功能并降低G中的CD36,但不能降低LG中的CD36。 TMZ促进了LG中丙泊酚的心脏保护作用。因此,低血糖的离体心脏通过增强FA氧化和TMZ补充而失去了对丙泊酚治疗的敏感性,从而恢复了对丙泊酚的敏感性。

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