Pulmonary arterial hypertension (PAH) is an aggressive disease with a 48% 3-year average survival. To study PAH, Sprague-Dawley rats were followed longitudinally for up to 4 weeks post monocrotaline injections. During open chest surgeries, blood pressure and flow from the pulmonary artery were measured simultaneously. Post hemodynamic studies, the right and left pulmonary arteries (RPA, LPA) were harvested for mechanical testing and structural investigation.
Mean pressure rose from 24.1±5.0 to 44.4±6.3 mmHg while flow overall remained constant during the disease progression. Using a 3-element Windkessel model, distal resistance was found to increase exponentially while compliance decreased linearly as a function of the disease, indicating a different remodeling process according to location.
From mechanical testing stiffness increase in the circumferential direction was found in advanced PAH, but it was only statistically significant in the RPA (Young’s modulus went from 3.4±3.1 to 22.9±12.7 kilo mmHg). Dampening properties of the LPA vessels decreased continuously as the disease progressed, while in the RPA the relaxation time initially increased and then decreased showing a different adaptive response.
Structure of the LPA and RPA changed in the advanced stage of PAH. In both vessels there was over a 10% increase in collagen content assessed by Masson’s Trichrome stained histology slides. Through multiphoton microscopy imaging analysis, collagen fibers were found to go from being crimped and randomly organized in the normotensive state to uncrimped and highly aligned towards the axial (0°) direction in hypertension. While the distribution of collagen fibers of both vessel types were aligned towards 14° (90° and -90° correspond to the circumferential direction), they had a second distribution aligned at -28° for the RPA and -8° for the LPA. This indicates that there is a second direction of preference in the RPA, while in the LPA it is mainly just one family of fibers.