Establishment of a mouse model for ischaemic heart failure induced by coronary microembolization via left ventricular oil injection

Over the past three decades, there has been a steady increase in clinical attention to ischaemic heart failure caused by coronary microembolization. Nonetheless, a suitable mouse model for studying this condition remains limited. In the present study, we developed a mouse model of coronary microembolization-induced ischaemic heart failure by injecting corn oil into the left ventricle. After oil injection, the photoacoustic microscopy system identified an immediate obstruction of blood flow in the microvessels of the left ventricle. One day after injection of 10-60 µL oil, mice exhibited a significant decrease in left ventricular ejection fraction and fractional shortening, along with an increase in left ventricular volume during systole and elevated serum creatine kinase MB levels. Oil injection also resulted in acute cardiomyocyte necrosis, apoptosis and inflammatory infiltration. After 1 month, the mouse model demonstrated a prolonged and dose-dependent reduction in heart function, in addition to significant increases in expression of the heart failure markers BNP and MYH7 and areas of cardiac fibrosis. Correspondingly, RNA sequencing revealed 126 differentially expressed genes in the oil-injected mice, which were enriched in pathways related to myocardial contraction, vasodilatation, myocardial fibrosis and chemotactic inflammation. Notably, treatment with nitroglycerin or sacubitril-valsartan was able to mitigate the decrease of heart function in the mouse model. In conclusion, we successfully established a coronary microembolization-induced mouse model of ischaemic heart failure by left ventricular injection of oil, which exhibited high sensitivity to nitroglycerin and sacubitril-valsartan.