(781.3) Role of cardiomyocytes in right ventricle viscoelasticity with pulmonary hypertension development

Poster Board Number: C48
Introduction: AAA has separate poster presentation times for odd and even posters.
Odd poster #s – 10:15 am – 11:15 am
Even poster #s – 11:15 am – 12:15 pm

Kristen LeBar (Colorado State University), Wenqiang Liu (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)

Background: The myocardium is viscoelastic, which means there exists elastic and viscous resistant forces during cardiac motion. It has been shown that cardiomyocyte (CM) or muscle fiber has significant viscoelasticity, and microtubule depolymerization via colchicine treatment reduces the CM’s viscoelasticity. However, most prior study is focused on the left ventricle, and the role of CM in right ventricle (RV) viscoelasticity in healthy and pulmonary hypertensive (PH) states is poorly understood. Our goal is to evaluate the contribution of CM to RV viscoelasticity in healthy and PH rats. We hypothesize that CM contributes to both healthy and PH RV viscoelasticity.

Methods: All procedures were approved by Colorado State University IACUC. 6-week-old male rats were treated with 3-week monocrotaline (MCT) (60 mg/kg) to induce PH, and intact healthy rats served as control. RV function was quantified by echocardiography and in vivo pressure-volume (PV) measurements. After euthanasia, RV free wall underwent equibiaxial stress relaxation in a relaxant bath to obtain passive, biaxial viscoelasticity pre and post colchicine treatment (0.3mM). The tissue was stretched at 20% of strain and with physiological ramp speed (5Hz). Relaxation modulus and normalized stress at 0.01 s were used to quantify elasticity and viscosity. Student t test was performed.

Results: In vivo RV function measurements showed the development of PH and RV failure in MCT rats (Table 1). Marked RV dilation and decreased fractional shortening confirmed the RV failure establishment. PV loop data with fewer samples (n=3) also implies declines in cardiac output, contractility (Ees) and ventricular-vascular coupling (Ees/Ea). At the baseline, PH development led to increased viscoelasticity in the RV (Fig. 1). Mechanical data before and after colchicine treatment showed reduced elasticity in both healthy and MCT RVs (Fig. 1Aamp;B). The percentage reduction in elasticity was similar between groups, indicating a similar contribution of CM to RV elasticity. Unexpectedly, we did not observe significant change in viscosity after colchicine treatment in both groups (Fig. 1Camp;D). Moreover, the control RVs were isotropic, whereas the MCT RVs showed marked anisotropy in elasticity (Fig. 1B).

Conclusion: Our results demonstrated similar impact of CM on RV viscoelasticity before and after PH development, despite the CM hypertrophy. Colchicine reduced elasticity in healthy and MCT RVs, but minimally changed RV viscosity. These findings will deepen the understanding of biomechanical mechanism of RV failure associated with viscoelastic changes.





Fig. 1. Effects of colchicine treatment on RV viscoelasticity. (A&B) Changes in RV elasticity measured by relaxation modulus at 0.01s in the control (A) and MCT (B) groups. (C&D) Changes in RV viscosity measured by normalized stress at 0.01s in the control (C) and MCT (D) groups. * p<0.05 vs baseline, & p<0.01 vs baseline, # p<0.05 vs L, † p<0.01 vs L.; Table 1: RV function alteration before and after 3 weeks MCT treatment. Results are mean±SE. * p<0.05 vs. CTL. # p < 0.1 vs. CTL.