Li Honglei, Huang Jiansheng, Liu Caihong, Zhang Zhentao, Song Kuiquan, Ma Ke, Dennewitz Connor W, Wang Shijun
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine; Department of Intensive Care Unit, Jinan Municipal Hospital of Traditional Chinese Medicine.
Department of Medicine, Vanderbilt University Medical Center.
J Vis Exp. 2021 Jun 10(172). doi: 10.3791/62540.
Ligation of the left anterior descending (LAD) coronary artery has been widely used to establish the rat model of heart failure (HF) post myocardial infarction (MI). However, the disadvantages of this model include high mortality rate after ligation and larger variations both in the infarct size and the degree of impaired cardiac function. In addition, a ventilator or exteriorization of the heart is indispensable for the previous models, which complicates the procedure during the ligation. In this study, we developed a reliable and reproducible model without the ventilator or exteriorization of the heart by ligating the LAD coronary artery. Four weeks after the procedure, we found that the serum concentrations of CK-MB, NT-proBNP, and Renin, which were used to assist diagnoses of MI and HF, were significantly higher in the MI group compared to the sham group. In contrast, the value of left ventricle ejection fraction (LVEF) in the MI group was obviously less than in the sham group. Furthermore, the infarct size and cardiac fibrosis area were individually confirmed and quantitatively analyzed by TTC staining and Masson's trichrome staining. Smaller variations were found in either infarct size or fibrosis area in the MI group, which helped to develop a reliable and reproducible model of HF post-MI. This new model of HF post-MI in the rat is vital for studying the potential mechanisms of MI and HF. This new method can be used to develop the new drug for treatment of MI and HF in rats by using pharmacological strategies.
结扎左冠状动脉前降支(LAD)已被广泛用于建立大鼠心肌梗死后心力衰竭(HF)模型。然而,该模型的缺点包括结扎后死亡率高,梗死面积和心功能受损程度的变异性较大。此外,先前的模型需要呼吸机或心脏外置,这使得结扎过程复杂化。在本研究中,我们通过结扎LAD冠状动脉,开发了一种无需呼吸机或心脏外置的可靠且可重复的模型。手术后四周,我们发现,用于辅助诊断心肌梗死和心力衰竭的血清肌酸激酶同工酶(CK-MB)、N末端B型利钠肽原(NT-proBNP)和肾素浓度,在心肌梗死组中显著高于假手术组。相比之下,心肌梗死组的左心室射血分数(LVEF)值明显低于假手术组。此外,通过TTC染色和Masson三色染色分别确认并定量分析梗死面积和心脏纤维化面积。心肌梗死组的梗死面积或纤维化面积的变异性较小,这有助于建立可靠且可重复的心肌梗死后心力衰竭模型。这种新的大鼠心肌梗死后心力衰竭模型对于研究心肌梗死和心力衰竭的潜在机制至关重要。这种新方法可用于通过药理学策略开发治疗大鼠心肌梗死和心力衰竭的新药。