1. Distinct right ventricle remodeling in response to pressure overload in the rat
- Author
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P. Mendes-Ferreira, Cláudia Sousa-Mendes, Carmen Brás-Silva, Miguel Mendes-Ferreira, Rui Adão, D. Santos-Ribeiro, Adelino F. Leite-Moreira, and C. Maia-Rocha
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Physiology ,Hypertension, Pulmonary ,Ventricular Dysfunction, Right ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Pulmonary artery banding ,03 medical and health sciences ,0302 clinical medicine ,Afterload ,Physiology (medical) ,medicine.artery ,Hypoxic pulmonary vasoconstriction ,Internal medicine ,Adaptation, Psychological ,Animals ,Medicine ,Arterial Pressure ,Myocytes, Cardiac ,Calcium Signaling ,Rats, Wistar ,Ventricular remodeling ,Pressure overload ,Hypertrophy, Right Ventricular ,Ventricular Remodeling ,business.industry ,medicine.disease ,Constriction ,Fibrosis ,Pulmonary hypertension ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Ventricle ,Pulmonary artery ,Ventricular Function, Right ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies.
- Published
- 2016
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