There is growing evidence of myocardial hysteresis and, recently, the viscoelasticity of healthy and pulmonary hypertensive (PH) right ventricle free walls (RVFW) has been studied by stress–relaxation. However, stress–relaxation does not fully capture the in vivo deformation of the tissue, and the changes in right ventricle hysteresis behavior with PH remain unknown. Our aim was to investigate RVFW biaxial hysteresis behavior with PH. We conducted equibiaxial cyclic sinusoidal tensile testing in healthy and PH rat RVFW tissues under 20% strain, with strain rates of 0.1&1 Hz (sub-physiological), and 5&8 Hz (physiological). Elastic modulus, loop height, stored and dissipated energies, the ratio of viscosity to elasticity (V/E), and the percentage of dissipated to total energy (damping) were derived. After PH, elastic modulus was elevated in both directions, while longitudinal loop height and stored and dissipated energies were increased (p < 0.05). Despite these individual changes in viscosity and elasticity, V/E ratio and damping were maintained. We further found frequency-dependent responses of V/E ratio and damping, and these were enhanced in the diseased RVs (p < 0.05 at 5&8 Hz) than healthy RVs (p < 0.05 only at 8 Hz). Finally, we observed significant correlations between individual mechanical properties and structural changes (collagen content/myofiber width), and the correlations were stronger in the longitudinal (p ⩽ 0.006) than circumferential (p < 0.05) direction. Moreover, collagen had a much greater contribution (p ⩽ 0.002) to tissue elasticity than myofiber (p ⩽ 0.02). Multiple linear regression analyses revealed a significant role of myofibers, not collagen content, in the tissue viscosity in both directions (p < 0.05). Our results suggest the importance of incorporating tissue viscoelastic properties into pathophysiology as well as the design of cardiac biomimetic materials for advancements in cardiac health.

Duchenne muscular dystrophy (DMD) is a severe genetic muscle disease caused by mutations of the dystrophin gene. Previous studies have detected senescent cells in the skeletal muscle of human DMD, dystrophin-deficient mice (Mdx), and rats. This study aimed to use a more severe dystrophin^-/-/utrophin^-/- (dKO-Hom) mouse model to identify which cells become senescent and if targeting cellular senescence can improve bone quality and muscle pathology in dKO-Hom mice. Immunohistochemistry of P21 and GLB1 revealed significantly more senescent cells in the skeletal muscle tissues of 4-week-old Mdx and dKO-Hom mice compared to WT mice, but not in the bone tissue. The senescent cells were predominantly macrophages (GLB1⁺/CD68⁺). Treatment of dKO-Hom mice with ruxolitinib improved spine L5 trabecular bone microarchitecture and ameliorated skeletal muscle histopathology by decreasing senescent macrophages (GLB1⁺CD68⁺, FUCA1⁺/CD68⁺ or P21⁺/CD68⁺) and senescent-associated phenotypes (SASP) such as macrophage migration inhibitory factor (MIF) in skeletal muscle. Ruxolitinib treatment also improved heart muscle pathology by decreasing senescent macrophages. Additionally, ruxolitinib treatment increased muscle grip strength and treadmill endurance of Mdx mice. Moreover, ruxolitinib significantly extended the lifespan of dKO-Hom mice after 12 days of treatment. Furthermore, treatment of dKO-Hom mice with ruxolitinib and deflazacort synergistically improved bone microarchitecture of the spine L5 vertebrate and the proximal tibia trabecular bone (BV/TV, Tb.N, Tb.Th) by increasing osteoblast cells and decreasing osteoclasts. Co-administration of ruxolitinib and deflazacort also synergistically ameliorated skeletal muscle and heart pathology. Therefore, targeting senescent cells with ruxolitinib represents a promising approach for treating DMD patients but warrants further studies in humans.

Guinea pigs used in research may experience inappetence or decreased intestinal motility, which can significantly compromise their welfare. This study evaluates the use of mirtazapine on appetite and intestinal motility in guinea pigs. An initial pharmacokinetics and efficacy study was performed using healthy male guinea pigs administered mirtazapine at 1.88, 3.75, or 7.5 mg orally once daily for four days (n = 6), in a crossover design where all animals received all doses. Body, feed, and fecal weights were taken daily for 4 days. There were no significant differences in weight gains, feed intake, or fecal output as compared to guinea pigs given saline only (n = 3). Blood was collected under anesthesia at 0, 0.5, 1, 2, 8, 12, and 24 h post-administration. Pharmacokinetic analysis completed after the first dose showed peak plasma levels at 30 min, then falling below the limit of detection between 8 h and 12 h at all doses. Based on the pharmacokinetic profile, a follow-up study was performed in another set of healthy male guinea pigs with every 8 h dosing at 1.88 mg orally for 5 days (n = 6). There was a significant increase in feed intake during mirtazapine administration as compared to baseline intake, but no significant difference in weight gains. This study shows that mirtazapine can be used as an appetite stimulant in guinea pigs but must be dosed at least every eight hours to be effective.