Introduction: Heart failure often involves right ventricular (RV) dysfunction due to pulmonary arterial hypertension (PAH), significantly influencing prognosis. However, RV dysfunction is frequently underrated compared to left ventricular (LV) dysfunction, and reliable animal models for studying biventricular heart failure remain insufficient. Hypothesis: Combined ligation of the left anterior descending coronary artery (LAD) with injection of vascular endothelial growth factor inhibitor (semaxinib, sugen) induces LV dysfunction with precapillary pulmonary arterial hypertension. Goals: We aimed to develop a new model of LV dysfunction induced by myocardial infarction (MI) combined with precapillary PAH. Methods: During the first week, LV dysfunction was induced in normotensive HanSD rats by LAD ligation. In the second week, PAH was induced by sugen injection (i.p., 100 mg/kg). Echocardiography, MRI, and pressure-volume analysis were performed at seven weeks to quantify RV and LV function. Organs were weighed and collected for further analyses, including histology. Results: Ejection fraction decreased significantly from 84 ± 5% to 36 ± 15% within two weeks post-MI (p < 0.001). LV anterior wall thickness decreased, and LV internal diameter increased at both end-systole and end-diastole. Heart weight was significantly greater in IM/placebo and IM/sugen groups than sham/placebo, mainly due to RV hypertrophy (+70 ± 27% IM/sugen vs. sham, p < 0.001). Pulmonary congestion occurred in the IM/sugen group (lung weight increased by 37 ± 26%, p < 0.01). Cardiac output significantly decreased in LV of IM/placebo rats, and in both ventricles of IM/sugen rats, accompanied by increased LV end-diastolic volume. RV systolic pressures were elevated significantly in IM/sugen (78 ± 10 mmHg, p < 0.001) but not in IM/placebo rats compared to sham (32 ± 9 mmHg). Both IM groups significantly decreased LV contractility (end-systolic elastance, preload recruitable stroke work). Interestingly, RV systolic function (dP/dt max) increased significantly in IM/sugen (2149 ± 400 vs. 1271 ± 348, p = 0.002) due to compensatory mechanisms, with no significant change in IM/placebo. Moreover, we created a prototype of a rat defibrillator that improved survival rate post-MI. Conclusion: We successfully established a rat model of myocardial infarction-induced LV dysfunction accompanied by precapillary PAH, suitable for studying heart failure with biventricular involvement.
Miklovič et al. (Fri,) studied this question.