谷氨酸补充剂对缺血和冷停搏大鼠离体灌流心脏的剂量反应研究。

A dose-response study of glutamate supplementation in isolated, perfused rat hearts undergoing ischaemia and cold cardioplegia.

机构信息

Department of Cardiothoracic and Vascular Surgery, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.

Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

出版信息

Eur J Cardiothorac Surg. 2018 Mar 1;53(3):664-671. doi: 10.1093/ejcts/ezx368.

DOI:10.1093/ejcts/ezx368

PMID:29069350

Abstract

OBJECTIVES

Several studies have reported superior post-cardioplegic recovery after glutamate supplementation. The optimum dose of glutamate supplementation is unknown. The purpose of this study was to find the optimal protective concentration of glutamate supplementation in a model of ischaemia/cardioplegia and reperfusion.

METHODS

Isolated rat hearts (n = 77) were perfused with the Krebs-Henseleit buffer. After stabilization, the hearts were subjected to 25 min of normothermic ischaemia followed by a single 3-min infusion of cold (4-6 °C) St. Thomas' Hospital II cardioplegia and 87 min of cardioplegic ischaemic arrest and 60 min of reperfusion. Sodium-l-glutamate was added to the perfusate (control group had zero glutamate) in increasing concentrations (0.01, 0.1, 1, 10, 20, 30 and 100 mM) and given throughout perfusion. Corresponding concentrations were added to the cardioplegic solution. A balloon in the left ventricle inserted via the left atrium measured left ventricular pressures isometrically. Left ventricular developed pressure was calculated. Myocardial exchange of glucose and lactate was measured prior to ischaemia and during reperfusion. Myocardial content of glycogen and glutamate was measured at the end of reperfusion.

RESULTS

During reperfusion left ventricular developed pressure increased (P < 0.0001) in groups supplemented with 0.1, 1.0, 10, 20 and 30 mM glutamate, whereas left ventricular end-diastolic pressure was attenuated (P = 0.008) when compared with the controls. No additional benefit on the continuous data left ventricular developed pressure and left ventricular end-diastolic pressure was observed with glutamate concentrations above 1 mM. Onset of LV pressure rise during the period of ischaemia was delayed by 100 mM of glutamate (P = 0.02). Myocardial content of glutamate was increased in a dose-related manner in Groups 10, 20, 30 and 100 compared with the control hearts (P < 0.0001). Glycogen was increased in the hearts supplemented with 100 mM of glutamate (P = 0.02).

CONCLUSIONS

Even low concentrations of l-glutamate improved postischaemic and post-cardioplegic heart function and 1 mM seems to be optimal.

摘要

目的

几项研究报告称，谷氨酸补充后心脏停搏后恢复更好。谷氨酸补充的最佳剂量尚不清楚。本研究的目的是在缺血/心脏停搏和再灌注模型中找到谷氨酸补充的最佳保护浓度。

方法

离体大鼠心脏（n=77）用 Krebs-Henseleit 缓冲液灌注。稳定后，心脏经历 25 分钟的常温缺血，随后进行 3 分钟的冷（4-6°C）圣托马斯医院 II 心脏停搏液输注，以及 87 分钟的心脏停搏缺血和 60 分钟的再灌注。将谷氨酸钠（控制组无谷氨酸）添加到灌注液中（0.01、0.1、1、10、20、30 和 100mM），并在整个灌注过程中给予。相应的浓度被添加到心脏停搏液中。左心房内插入的气球通过左心室测量等容左心室压力。计算左心室发展压。在缺血前和再灌注期间测量葡萄糖和乳酸的心肌交换。再灌注结束时测量糖原和谷氨酸的心肌含量。

结果

再灌注期间，补充 0.1、1.0、10、20 和 30mM 谷氨酸的组左心室发展压升高（P<0.0001），而与对照组相比，左心室舒张末期压降低（P=0.008）。当谷氨酸浓度高于 1mM 时，对连续数据左心室发展压和左心室舒张末期压没有额外的益处。谷氨酸 100mM 组左心室压力升高开始时间延迟（P=0.02）。与对照组相比，10、20、30 和 100 组心肌谷氨酸含量呈剂量依赖性增加（P<0.0001）。补充 100mM 谷氨酸的心脏糖原增加（P=0.02）。