Study of the Effect of Treatment With Atrial Natriuretic Peptide (ANP) and Cinaciguat in Chronic Hypoxic Neonatal Lambs on Residual Strain and Microstructure of the Arteries

Navarrete, Álvaro; Chen, Zhuoming; Aranda, Pedro; Poblete, Daniel; Utrera, Andrés; García‐Herrera, Claudio; Gonzaléz‐Candia, Alejandro; Beñaldo, Felipe A.; Ebensperger, Germán; Reyes, Roberto V.; Herrera, Emílio; Llanos, Aníbal J.

doi:10.3389/fbioe.2020.590488

Cited by 4 publications

(7 citation statements)

References 70 publications

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“…All ex vivo tests (biomechanical & functional) were carried out in the aorta within 1 h after euthanasia. All mechanical tests described below were performed maintaining the specimens submerged in a Ca-free Krebs buffer at 38 °C to replicate physiological conditions 4 , 24 .…”

Section: Methodsmentioning

confidence: 99%

“…To observe the longitudinal stretch under in-vivo configurations, an axial pre-stretch test was carried out (Fig. 2 a) 4 , 24 . Once euthanasia was performed, the aorta artery length was measured, inside the body of the individual (in-situ state).…”

Section: Methodsmentioning

confidence: 99%

“…Hypobaric hypoxia (HH), particularly referred to high altitude hypoxia, is related to a decrease in the atmospheric or barometric pressure (BP) relative to sea-level conditions, inducing several multisystemic health issues and potential risks 2 . The effect of HH by high altitude conditions is physiologically and clinically relevant over 2500 m.a.s.l, due to a drop in arterial oxygen pressure (PaO 2 ) and saturation (SaO 2 ), whose factors, in combination with the system hemodynamical and respiratory responses, conditions the physiological alterations regarding HH 3 , 4 . According to previous studies, exposure to long-term HH may lead to high-altitude illness , such as Acute Mountain Sickness (AMS), High Altitude Pulmonary Edema (HAPE) and High Altitude Cerebral Edema (HACE) 5 , 6 , among other pathophysiological conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Remodeling and mechanical properties alterations of biological tissues, when faced to environmental changes, are related with changes in the different microstructural components. For instance, in arteries, these changes are associated to collagen and elastin deposition, and smooth muscle cells (SMC) densities, with detrimental effects associated with vascular impairment and cardiovascular diseases 4 .…”

Section: Introductionmentioning

confidence: 99%

“…The authors concluded that an enhanced elastin and collagen deposits, and thicknening of the arterial wall was associated with an increased stiffness due to hypoxia. On a different study, Navarrete et al 4 determined residual strain levels, through the ring opening test and pre-stretching test, in sheep exposed to chronic hypoxia during gestation and treated with experimental vasodilators. The authors studied the effects on neonates born from hypoxic ewes, establishing a relationship between medical treatments and beneficial mechanical response of the arterial wall.…”

Section: Introductionmentioning

confidence: 99%

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Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

Utrera

Navarrete

Gonzaléz‐Candia

et al. 2022

Sci Rep

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High altitude hypoxia is a condition experienced by diverse populations worldwide. In addition, several jobs require working shifts where workers are exposed to repetitive cycles of hypobaric hypoxia and normobaric normoxia. Currently, few is known about the biomechanical cardiovascular responses of this condition. In the present study, we investigate the cycle-dependent biomechanical effects of intermittent hypobaric hypoxia (IHH) on the thoracic aorta artery, in terms of both structure and function. To determine the vascular effects of IHH, functional, mechanical and histological approaches were carried out in the thoracic aorta artery, using uniaxial, pre-stretch, ring opening, myography, and histological tests. Three groups of rats were established: control (normobaric normoxia, NN), 4-cycles of intermittent hypoxia (short-term intermittent hypobaric hypoxia, STH), and 10-cycles of intermittent hypoxia (long-term intermittent hypobaric hypoxia, LTH). The pre-stretch and ring opening tests, aimed at quantifying residual strains of the tissues in longitudinal and circumferential directions, showed that the hypoxia condition leads to an increase in the longitudinal stretch and a marked decrease of the circumferential residual strain. The uniaxial mechanical tests were used to determine the elastic properties of the tissues, showing that a general stiffening process occurs during the early stages of the IH (STH group), specially leading to a significative increase in the high strain elastic modulus ($$E_{2}$$ E 2 ) and an increasing trend of low strain elastic modulus ($$E_{1}$$ E 1 ). In contrast, the LTH group showed a more control-like mechanical behavior. Myography test, used to assess the vasoactive function, revealed that IH induces a high sensitivity to vasoconstrictor agents as a function of hypoxic cycles. In addition, the aorta showed an increased muscle-dependent vasorelaxation on the LTH group. Histological tests, used to quantify the elastic fiber, nuclei, and geometrical properties, showed that the STH group presents a state of vascular fibrosis, with a significant increase in elastin content, and a tendency towards an increase in collagen fibers. In addition, advanced stages of IH (LTH), showed a vascular remodeling effect with a significant increase of internal and external diameters. Considering all the multidimensional vascular effects, we propose the existence of a long-term passive adaptation mechanism and vascular dysfunction as cycle-dependent effects of intermittent exposures to hypobaric hypoxia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

Utrera

Navarrete

Gonzaléz‐Candia

et al. 2022

Sci Rep

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Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat

Laubrie

Bezmalinovic

García‐Herrera

et al. 2023

Journal of Biomechanics

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Analysis of the geometrical influence of ring-opening samples on arterial circumferential residual stress reconstruction

Inostroza,

Utrera,

García-Herrera

et al. 2023

Front. Bioeng. Biotechnol.

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This work consists of analyzing the impact of geometrical features (thickness and curvature) on the estimation of circumferential residual stresses in arteries. For this purpose, a specific sample of lamb abdominal artery is chosen for analysis and, through computational tools based on Python libraries, the stress-free geometry is captured after the ring opening test. Numerical simulations are then used to reconstruct the sample in order to estimate the circumferential residual stresses. Then, four stress-free geometry models are analyzed: an ideal geometry, i.e., constant curvature and thickness; a constant curvature and variable thickness geometry; a variable curvature and constant thickness geometry; and a variable curvature and thickness geometry. The numerical results show that models perform well from a geometric point of view, where the most different feature was the closed outer perimeter that differs about 14% from the closed real sample. As far as residual stress is concerned, differences up to 198% were found in more realistic models taking a constant curvature and thickness model as reference. Thus, the analysis of a realistic geometry with highly variable curvature and thickness can introduce, compared to an idealized geometry, significant differences in the estimation of residual stresses. This could indicate that the characterization of arterial residual stresses is not sufficient when considering only the opening angle and, therefore, it is also necessary to incorporate more geometrical variables.

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Study of the Effect of Treatment With Atrial Natriuretic Peptide (ANP) and Cinaciguat in Chronic Hypoxic Neonatal Lambs on Residual Strain and Microstructure of the Arteries

Cited by 4 publications

References 70 publications

Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

Hyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat

Analysis of the geometrical influence of ring-opening samples on arterial circumferential residual stress reconstruction

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