Contractile Adaptation Of The Right Ventricular Myocardium In Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) is characterized by increased right ventricular (RV) afterload inducing notable biomechanical remodeling in the RV free wall (RVFW) myocardium. While changes in the passive behavior of the RVFW have been studied, its contractile adaptations in PH remain to be investigated. Methods: Two sugen-hypoxia models were developed by injecting SU5416 into Sprague Dawley (SD) and Fischer (CDF) rats (n=4 each) and placing them in a hypoxia chamber for 3 weeks, followed by 1 week of normoxia. Wild-type rats (n=4), injected with vehicle and kept in normoxia, were used as controls. Right heart catheterization was perfomed at week 4. RVFW samples were skinned in 10% Triton. Samples were activated at pCa 4.5. Mechanical tests were performed isometrically at 20% stretch. Circumferential and longitudinal stresses were summed to report ensemble stress. Results: RV systolic pressure and stroke volume showed significant increase and decrease in both PH groups, respectively, compared to controls (Figs. 1A, B). While increases in initial stress, representing the passive behavior, did not reach significance in either PH group (Fig. 1C), total stress, representing the combined passive and active behavior, increased significantly only in CDF-PH group (Fig. 1D), known to exhibit a more maladaptive RV remodeling compared to SD-PH. Select stresses are shown in Figs. 1E, F. Conclusions: While elevated passive stresses in the RVFW are commonly reported in PH, the measurement of contractile stresses is essential to properly assess the adaptation of the RV. Further studies are needed to determine the role of passive vs. active stresses in the outcome of RV remodeling.