Wenqiang Liu (Colorado State University), Kristen LeBar (Colorado State University), Kellan Roth (Colorado State University), Matt Ahern (Colorado State University), Erith Evans (Colorado State University), Jassia Pang (Colorado State University), Jessica Ayers (Colorado State University), Adam Chicco (Colorado State University), Zhijie Wang (Colorado State University)
Introduction: Right ventricle failure (RVF) secondary to pulmonary hypertension (PH) is a key risk factor for PH patients. The RV mechanical behavior is an important determinant of its function. However, compared to the nonlinear anisotropic elasticity, it remains unclear how RV biaxial viscoelasticity alters with PH. Our goal is to characterize the changes in RV biaxial viscoelasticity at rest and exercise conditions in response to PH. We hypothesize that PH alters RV anisotropy, viscoelasticity type and the response to exercised heart rate.
Methods: All procedures were approved by Colorado State University IACUC. Briefly, adult male rats were treated by monocrotaline (MCT, 60 mg/kg) for 3 weeks to induce PH. Healthy rats were used as controls (CTL). After euthanasia, ex vivo equibiaxial stress relaxation tests were performed to quantify the RV viscoelasticity. The outflow track direction was defined as the longitudinal direction.
Two sets of stress relaxation tests were included: 1) Using different strain levels (3-15%) at three fixed ramp speeds (2, 5 and 8 Hz); and 2) using different ramp speeds (0.1-8 Hz) mimicking non-physiological and physiological heart rates at rest and exercise at a fixed strain level (20%). The relaxation modulus and the normalized stress were used to indicate the RV viscoelasticity. The logarithmic scale plot from the first set data was used to analyze the type of RV viscoelasticity. A student’s t-test was performed and plt;.05 was treated as significant.
Results: The establishment of RVF was confirmed by echocardiography. As shown in Fig. 1, we observed frequency-dependent viscoelasticity in both groups and directions, except for the elasticity of CTL RV in C direction. PH development led to more significant increase in viscoelasticity in L direction compared to the C direction (Fig. 1). The examination of the viscoelasticity at physiological strain-rates showed that compared to the CTL RV, the MCT RV 1) became anisotropic in elasticity and stiffer in the L direction (Fig. 2A); 2) had increased viscosity in the L direction (Fig. 2B); and 3) had reduced viscoelasticity from the rest to exercise states (Fig. 2). Our results suggested that during exercise, the healthy RV’s viscoelastic behavior was maintained, whereas the diseased RV had decreased viscoelasticity. Finally, we found that the CTL RV was quasi-linear viscoelastic at all testing frequencies, whereas the MCT RV was nonlinear viscoelastic in all testing conditions, except for the L behavior at sub-physiological frequency. Therefore, PH changed the RV viscoelasticity from a quasi-linear to fully nonlinear type.
Conclusion: This is the first report of RV biaxial viscoelasticity changes with PH in rats. In the diseased RV, increased viscoelasticity and altered anisotropy and viscoelasticity type were observed, and the viscoelasticity was reduced during exercise. These novel findings improve our understanding of RV biomechanics in response to pulsatile mechanical loadings at rest and exercise conditions.
Fig. 1. Frequency-dependent viscoelastic behavior of the CTL and MCT RVs. (A-B) frequency-dependent elastic behavior in each direction; (C-D) frequency-dependent viscous behavior in each direction. * < 0.05 and ** < 0.01 vs 0.1Hz, respectively; & < 0.05 and && < 0.01 vs 1Hz, respectively; ^ < 0.05 and ^^ < 0.01 vs 2Hz, respectively; # < 0.05 and ## < 0.01 vs 5Hz, respectively. N=4 for the CTL group and N=5 for the MCT group.; Fig. 2. At rest condition (5 Hz): (A) RV elasticity increased in the longitudinal direction and RV anisotropy changed with PH development, (B) RV viscosity increased in the longitudinal direction with PH development. Exercise condition (8 Hz) reduced elasticity (A) and viscosity (B) in the MCT RVs, but it did not change viscoelasticity in CTL RVs.
