Browsing by Author "Llanos, Anibal J."

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    Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat
    (2023) Laubrie, Joan D.; Bezmalinovic, Alejandro; Garcia-Herrera, Claudio M.; Celentano, Diego J.; Herrera, Emilio A.; Avril, Stephane; Llanos, Anibal J.
    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.
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    Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep
    (INT PEDIATRIC RESEARCH FOUNDATION, INC, 2008) Herrera, Emilio A.; Ebensperger, German; Krause, Bernardo J.; Riquelme, Raquel A.; Reyes, Roberto V.; Capetillo, Maria; Gonzalez, Sergio; Parer, Julian T.; Llanos, Anibal J.
    Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small Pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates.