Goergens Jessica I, Heinen Nicole M, Zoller Jan, Preckel Benedikt, Bauer Inge, Huhn Ragnar, Ebel Dirk, Raupach Annika
Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.
Department of Emergency Medicine, General Hospital Viersen (AKH), Viersen, Germany.
Shock. 2020 May;53(5):637-645. doi: 10.1097/SHK.0000000000001406.
Ischemic preconditioning (IPC) protects the myocardium against ischemia/reperfusion injury. Evidence suggests that hyperglycemia inhibits IPC-induced cardioprotection. The effects of hyperglycemia initiated during different phases of IPC on myocardial injury were characterized with emphasis on apoptosis and aggregation of polymorphonuclear granulocytes (PMN).
Male Wistar rats were subjected to 35 min of myocardial ischemia and 2 h of reperfusion. Control animals were not further treated. IPC was induced by three cycles of 3 min ischemia and 5 min of reperfusion before major ischemia. Hyperglycemia (blood glucose more than 22.2 mmol/L) was induced by glucose administration with or without IPC during different phases (trigger- (before ischemia), mediator- (during ischemia), early reperfusion-phase). One additional group received an anti-PMN-antibody before ischemia. Infarct size was quantified by triphenyltetrazolium chloride staining. Cytochrome C release and B-cell lymphoma two (Bcl-2) expression were assessed by western blot analysis. Poly-ADP-Ribose staining and PMN accumulation were quantified with immunohistochemistry and histochemistry.
IPC reduced infarct size compared with control. Hyperglycemia completely abolished IPC-induced cardioprotection independent of the time point of initiation. Hyperglycemia before and during major ischemia but without IPC also slightly reduced infarct size. IPC reduced the accumulation of PMNs. This effect was reversed by hyperglycemia during trigger- and mediator-phase but not by hyperglycemia during reperfusion. Hyperglycemia alone had no effect on PMN accumulation. In all treatment groups, signs of myocardial apoptosis were reduced compared with control. IPC alone, combined with hyperglycemia and anti-PMN treatment, reduced apoptosis by a Bcl-2-associated mechanism. Hyperglycemia alone reduced apoptosis by a Bcl-2-independent pathway.
Hyperglycemia inhibits IPC-induced cardioprotection independent of its onset. Furthermore, hyperglycemia prevents apoptosis and IPC-induced reduction of PMN aggregation.
缺血预处理（IPC）可保护心肌免受缺血/再灌注损伤。有证据表明，高血糖会抑制IPC诱导的心脏保护作用。本研究旨在明确在IPC不同阶段开始的高血糖对心肌损伤的影响，重点关注凋亡和多形核粒细胞（PMN）聚集情况。
雄性Wistar大鼠经历35分钟心肌缺血和2小时再灌注。对照组动物不做进一步处理。在主要缺血前，通过3分钟缺血和5分钟再灌注的三个周期诱导IPC。在不同阶段（触发期 - 缺血前、介质期 - 缺血期间、早期再灌注期）通过给予葡萄糖诱导高血糖（血糖超过22.2 mmol/L），同时或不进行IPC。另外一组在缺血前接受抗PMN抗体治疗。通过氯化三苯基四氮唑染色定量梗死面积。通过蛋白质免疫印迹分析评估细胞色素C释放和B细胞淋巴瘤-2（Bcl-2）表达。用免疫组织化学和组织化学法定量聚ADP核糖染色和PMN聚集情况。
与对照组相比，IPC减小了梗死面积。高血糖完全消除了IPC诱导的心脏保护作用，且与开始的时间点无关。主要缺血前和期间的高血糖但无IPC也略微减小了梗死面积。IPC减少了PMN的聚集。在触发期和介质期的高血糖逆转了这种作用，但再灌注期的高血糖未逆转。单独高血糖对PMN聚集无影响。与对照组相比，所有治疗组心肌凋亡迹象均减少。单独IPC、联合高血糖和抗PMN治疗通过Bcl-2相关机制减少凋亡。单独高血糖通过Bcl-2非依赖途径减少凋亡。
高血糖抑制IPC诱导的心脏保护作用，且与发病时间无关。此外，高血糖可预防凋亡和IPC诱导的PMN聚集减少。
