Assessment of Experimental Permanent Coronary Artery Ligation Using Echocardiography and Invasive Real-Time Pressure-Volume (PV): A Practical Tips to Evaluate Rat Hemodynamics

摘要

Background: Rat permanent coronary artery ligation is surgical model mimicking coronary artery ischemia and myocardial infarct (MI) injury, both sequels of coronary artery disease (CAD). The aim of this publication is to provide comprehensive, detailed description of rat load-dependent and independent hemodynamic assessment at baseline and at 28 days post-myocardial ischemia and remodeling. Materials and Methods: the detailed depiction of rat-MI model is followed by a thorough assessment of hemodynamics by two-dimensional (2D) echocardiography and invasive pressure-volume (PV) catheterization. Results: Quantification of post-MI using 2D M-mode showed a significant increase in end-systolic and end-diastolic dimensions with a decrease of fractional shortening. PV load-dependent hemodynamics at 28 days showed a rightward shift of PV loop on the volume axis, characterized by an increase of LVEDV; (319±73 vs. 215±79 μl; P<0.001) and the LVESV (157±39 vs. 57±28 μl; P<0.001). Both dpdtmax and ESP were significantly influenced by decreasing the number of myocytes, leading to a significant decrease of dpdtmax (5786±1443 vs. 9609±4126 mmHg; P<0.01) and ESP (91.5±12 vs. 108.2±13 mmHg; P<0.001). Loss of contractile myocytes had an effect on the cardiac output (CO) and ejection fraction (EF); (49±12 vs. 68±3.5 ml/min; P<0.05) and (50±8.5 vs. 76±4.9 % P<0.001). Diastolic dysfunction had a major influence on LV lusitropy at day 28 post-MI characterized by prolonged LV filling at higher LVEDP (9.1±2.9 vs. 5.18±2.5 % P<0.01), higher Tau values, time to peak filling and dpdt min (-4850±1062 vs. 5876±1443 mmHg; P<0.001). Using histopathology, calculated HW/BW ratio (g/mg) (3.1±0.22 vs. 3.82±0.39; P<0.001), reflected hypertrophy of post-remodeled myocardium. Conclusion: Heart failure (HF) post-permanent coronary artery ligation influences both systolic and diastolic hemodynamics. Comprehensive assessment of modeled HF using load-dependent and independent indices enables its clinical translation.