西那卡塞治疗的缺氧主动脉的超弹性和损伤特性
Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat.
作者信息
Laubrie Joan D, Bezmalinovic Alejandro, García-Herrera Claudio M, Celentano Diego J, Herrera Emilio A, Avril Stéphane, Llanos Aníbal J
机构信息
Departamento de Ingeniería Mecánica, Facultad de Ingeniería, Universidad de Santiago de Chile, Santiago, Chile.
Departamento de Ingeniería Mecánica, Facultad de Ingeniería, Universidad de Santiago de Chile, Santiago, Chile.
出版信息
J Biomech. 2023 Jan;147:111457. doi: 10.1016/j.jbiomech.2023.111457. Epub 2023 Jan 16.
Chronic hypoxia during gestation and postnatal period induces pulmonary hypertension, aorta stiffening and vascular remodeling. In this study, we hypothesized that a postnatal treatment with Cinaciguat, a guanylate cyclase activator, may improve the vascular function by enhancing NO-sGC pathways that induce vasodilation. To assess this, we collected aortas from six lambs gestated, born and raised at 3600 masl. Half of these lambs received a Cinaciguat postnatal treatment, while the other half was used as control (vehicle). Uniaxial tension was applied on samples of each group of aortas (control and Cinaciguat-treated) through cyclic loading. The obtained stress-stretch curves were used to identify constitutive parameters of a hyperelastic damage model. These material constants allowed us to assess the softening/dissipation behavior and to characterize the treatment effects. Results showed that Cinaciguat has an effect on the damage behavior at large strains, altering the damage onset under uniaxial tension. We conclude that Cinaciguat, as a vasodilator, can prevent the very early effects of vascular remodeling caused by perinatal hypoxia, and improve the aortic-tissue damage properties of hypoxic lambs.
孕期和产后的慢性缺氧会导致肺动脉高压、主动脉硬化和血管重塑。在本研究中,我们假设用鸟苷酸环化酶激活剂西那吉多进行产后治疗,可能通过增强诱导血管舒张的一氧化氮-可溶性鸟苷酸环化酶(NO-sGC)途径来改善血管功能。为了评估这一点,我们从在海拔3600米处妊娠、出生和饲养的6只羔羊身上采集了主动脉。其中一半羔羊接受了西那吉多产后治疗,另一半作为对照(赋形剂)。通过循环加载对每组主动脉样本(对照和西那吉多治疗组)施加单轴张力。获得的应力-应变曲线用于确定超弹性损伤模型的本构参数。这些材料常数使我们能够评估软化/耗散行为并表征治疗效果。结果表明,西那吉多在大应变下对损伤行为有影响,改变了单轴张力下的损伤起始点。我们得出结论,西那吉多作为一种血管舒张剂,可以预防围产期缺氧引起的血管重塑的早期影响,并改善缺氧羔羊的主动脉组织损伤特性。