Abstract Body: Introduction. Pulmonary hypertension (PH) is characterized by an elevation in mean pulmonary arterial pressure (mPAP) and affects 1% of the world population. Stiffening of the pulmonary artery (PA) is known to contribute to PA pressure overload. Studies have commonly used pulmonary vascular compliance (PVC) to quantify alterations in the mechanical behavior of the PA. However, PVC fails to account for directional changes in PA mechanics (i.e., anisotropy) that affect the pulsatile behavior of afterload. Our objective in this study was to investigate the directionality of PA stiffening due to PH.
Methods. The animal model of PH was established by administering a single dose of SU5416 (20 mg/kg, sc) to CDF rats (n = 8). The animals were placed in a hypoxia chamber (10% O2) for 3 weeks, followed by one week of normoxia. Control rats (n = 8) were maintained in normoxia at all times. Each group consisted of half males and half females. The main PA tissue specimens were harvested and characterized through mechanical tests. Tissue stiffness was calculated as the slope of the stress-strain curve along the circumferential and longitudinal directions at a large strain for the PA specimens.
Results. PH caused a significant increase in PA systolic pressure (Fig. 1A) and a significant decrease in stroke volume (Fig. 1B), with the changes being comparable in both sexes. The increase in circumferential stiffness was not significant in either sex (Fig. 1C), but the increase in longitudinal stiffness in PH was significant across both sexes (Fig. 1D).
Conclusions. These findings indicate that stiffening of the main PA tissue was elevated in a single direction, suggesting a directional bias in structural remodeling of the PA towards the longitudinal direction. Our results underscore the need for higher-fidelity, tissue-level biomarkers that could provide additional insight into the vascular remodeling in PH. A detailed analysis of the PA anisotropy-RV afterload relationship could further delineate factors contributing to RV-PA uncoupling in PH.