In vivo growing leporine model of pulmonary artery banding induces inflammation and vascular remodeling via pathways conserved across species

Objectives: Characterization of pulmonary artery banding in a growing leporine model with comparison to human tissue has yet to be published. We hypothesized that there would be inflammatory changes that occur to the myocardium despite small changes to the gradients across the pulmonary arteries in rabbits that underwent pulmonary artery banding. Additionally, we analyzed tissue from humans to determine whether these are pathways preserved across species. Methods: Female 2-month-old New Zealand white rabbits were anesthetized, and a band was placed loosely around the main pulmonary artery (n = 4). The rabbits underwent either echocardiographic or magnetic resonance imaging, and the hearts were harvested when the rabbits weighed approximately 3.9 kg. Right ventricle samples from humans (tissues that would have been discarded otherwise) were obtained for comparison. Results: The right ventricles of the rabbits that underwent pulmonary artery banding exhibit significantly more CD31+α-SMA+ expression than the control rabbits (P = .03). The right ventricles at the level of the infundibulum also had significantly more fibrosis than the control rabbit confirmed with Masson's trichrome and picrosirius red staining (P = .03 and P < .001, respectively) and significantly more transforming growth factor-β+ expression (P = .04). Human samples demonstrate similar findings. Conclusions: Even with minimal changes to the pulmonary artery gradient, growing leporine rabbits exhibit significant inflammation, vascular remodeling, and fibrosis in the right ventricle in response to pulmonary artery banding. These changes are conserved across species, because we found that the right ventricles of patients with pulmonary arterial hypertension or that had undergone pulmonary artery banding also exhibit similar expression of inflammation, vascular remodeling, and fibrosis.