Initial Body Weight as an Important Factor for Improving the Reliability and Translational Relevance of the Preclinical Monocrotaline-Induced Rat Pulmonary Hypertension Model

Animal preclinical experiments in pulmonary hypertension (PH) need to be conducted with detailed methodological rigor to improve their translational relevance. One of its crucial yet insufficiently studied aspects is animal body weight (BW). Thus, our study aimed to examine the influence of initial BW on the severity of PH development induced by monocrotaline (MCT) and the effectiveness of the reference combined therapy (ambrisentan and tadalafil given for 21 days). Male rats were divided into three weight Sets: Set I (200-219 g); Set II (220-239 g); and Set III (240-259 g), after which, MCT-PH was induced. The measurements taken included in vivo echocardiographic evaluations, ex vivo functional experiments (on isolated right ventricle papillary muscles and pulmonary arteries), and histological and morphometric assessments. In all three Sets of animals, we noticed evidence of PH development. More pronounced changes confirming the severity of PH were observed in Set II compared to Sets I and III. The effectiveness of the reference therapy was also most evident in Set II, where the reversal of PH-related aggravations was best documented. We demonstrated that both the severity of MCT-induced PH in rats and the effectiveness of the reference combined therapy strongly depend on the animals' initial BW.