[胰岛素对犬急性心肌缺血再灌注实验中心脏功能及冠脉循环的影响]

[Effects of insulin on cardiac function and coronary circulation in acute myocardial ischemia and reperfusion experiment with dogs].

作者信息

Ma Heng, Huo Jian-hua, Zhang Hang-xiang, Bian Jie-fang, Wang Yue-min, Xiong Li-ze, Guo Wen-yi, Wang Hai-chang, Gao Feng

机构信息

Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2006 Nov 28;86(44):3128-32.

PMID:17313765

Abstract

OBJECTIVE

To study the effect of insulin on cardiac functional recovery, coronary blood flow (CBF), coronary arterial function and coronary vascular endothelial cell apoptosis following acute myocardial ischemia/reperfusion (MI/R).

METHODS

In adult dogs, the left anterior descending coronary artery (LAD) was partially occluded (80% reduction in its blood flow) for 50 min and reperfused for 4 h. Vehicle (0.9% NaCl), GIK (glucose: 250 gxL(-1), insulin: 60 UxL(-1), potassium: 80 mmolxL(-1)), or GK (glucose: 250 gxL(-1), potassium: 80 mmolxL(-1)) were intravenously infused (2 mlxkg(-1)xh(-1)) 5 min before reperfusion, and CBF and left ventricular pressure were monitored. At the end of 4 h reperfusion period, coronary arteries were isolated, and the coronary vascular dysfunction, nitric oxide (NO) production and endothelial apoptosis were determined.

RESULTS

During reperfusion, compared with the vehicle, GIK increased CBFLAD (19.2 ml/min +/- 2.2 ml/min) vs (14.6 ml/min +/- 1.8 ml/min) of vehicle at the end of reperfusion, P < 0.05, improved recovery of LVSP and +/- LVdP/dtmax. In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium dependent vasorelaxation, decreased total NO production, and endothelial cell apoptosis as determined by TUNEL staining. Reperfusion with GIK, but not GK, markedly improved the endothelium-dependent vasorelaxation (80.3% +/- 3.8%) vs. vehicle (28.1% +/- 2.3%, P < 0.01) of coronary artery in response to ACh. GIK significantly increased total NO production (17.19 micromol/L +/- 2.18 micromol/L) versus vehicle (4.74 micromol/L +/- 2.01 micromol/L, P < 0.01) and inhibited apoptosis in coronary arterial endothelial cell (12% +/- 4%) vs vehicle (45% +/- 7%, P < 0.01). GK failed to show any significant vasculoprotection against MI/R-induced coronary vascular injury.

CONCLUSION

These results demonstrate that insulin exerts cardioprotective effect by increasing CBF, reducing coronary artery injury and improving cardiac functional recovery during reperfusion, which may be partly attributable to the coronary vasculoprotective effect of insulin. The insulin-induced, NO-mediated anti-endothelial apoptotic effect may play a critical role in the insulin-induced coronary artery protective effect in MI/R.

摘要

目的

研究胰岛素对急性心肌缺血/再灌注（MI/R）后心脏功能恢复、冠状动脉血流量（CBF）、冠状动脉功能及冠状动脉血管内皮细胞凋亡的影响。

方法

在成年犬中，将左冠状动脉前降支（LAD）部分闭塞（血流量减少80%）50分钟，然后再灌注4小时。在再灌注前5分钟静脉输注溶媒（0.9%氯化钠）、GIK（葡萄糖：250 g/L，胰岛素：60 U/L，钾：80 mmol/L）或GK（葡萄糖：250 g/L，钾：80 mmol/L）（2 ml/kg/h），并监测CBF和左心室压力。在再灌注4小时结束时，分离冠状动脉，测定冠状动脉血管功能障碍、一氧化氮（NO）生成及内皮细胞凋亡情况。

结果

再灌注期间，与溶媒组相比，GIK使再灌注结束时的CBFLAD增加（19.2 ml/min ± 2.2 ml/min），而溶媒组为（14.6 ml/min ± 1.8 ml/min），P < 0.05，改善了LVSP及±LVdP/dtmax的恢复。体内缺血/再灌注导致显著的冠状动脉血管内皮功能障碍，表现为内皮依赖性血管舒张减弱、总NO生成减少，以及通过TUNEL染色确定的内皮细胞凋亡。用GIK而非GK进行再灌注，可显著改善冠状动脉对乙酰胆碱的内皮依赖性血管舒张（80.3% ± 3.8%），而溶媒组为（28.1% ± 2.3%，P < 0.01）。GIK显著增加总NO生成（17.19 μmol/L ± 2.18 μmol/L），而溶媒组为（4.74 μmol/L ± 2.01 μmol/L，P < 0.01），并抑制冠状动脉内皮细胞凋亡（12% ± 4%），而溶媒组为（45% ± 7%，P < 0.01）。GK未能显示出对MI/R诱导的冠状动脉血管损伤有任何显著的血管保护作用。