Key result
Tested drugs for pulmonary arterial hypertension showed a 73.1% concordance in results between pulmonary hypertension models and pulmonary artery banding animals.
Why the study?
Right ventricle function is the main prognostic factor in pulmonary hypertension, but results from rodent models often fail to translate to clinical trials.
Many drugs currently under research for PAH have cardioprotective effects on right ventricular function in animal models, but methodological uniformization is needed to improve translation to clinical trials.
Supports dual pulmonary-RV benefits in preclinical models; leaves open translation to human PH trials.
Pulmonary hypertension (PH) is a progressive condition that affects the pulmonary vessels, but its main prognostic factor is the right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate to clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and improved RV structure and function in PAB animals. PH models and PAB animals frequently exhibited similar results (73.1% concordance). Macitentan, sildenafil, and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Results are frequently not consistent with other studies, possibly due to the methodology, which greatly varied. Some research groups start treating the animals immediately, and others wait up to 4 weeks from model induction. Treatment duration and choice of anaesthetic are other important differences. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. However, a uniformization of methods may increase comparability between studies and, thus, improve translation to clinical trials.
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Balsa et al. (2023) conducted a review in Pulmonary Arterial Hypertension. Pharmacological interventions for PAH was evaluated on Concordance of results between PH models and PAB animals. Tested drugs for pulmonary arterial hypertension showed a 73.1% concordance in results between pulmonary hypertension models and pulmonary artery banding animals.
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