Abstract
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}) and an increasing trend of low strain elastic modulus (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.
Highlights
High altitude hypoxia is a condition experienced by diverse populations worldwide
Farías et al.[16], describe an acclimatization process that causes a multisystemic adjustment over a given time, in which pulmonary vascular tone, cardiovascular response, exercise response, and oxidative stress are affected by the intermittent hypobaric hypoxia (IHH)
Based on the evidence reported by different a uthors[38–40], which established physiological adaptation in response to hypoxia, along with the evidence of mechanical changes described above, we extend the concept of adaptation in a mechanical sense, when hypoxia cyclical exposures are increased, due to the similarity of the elastic properties among NN and long-term hypoxia (LTH) groups, and a previous increment of stiffness in an intermediate stage (STH)
Summary
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. One specific IH model corresponds to chronic intermittent hypoxia (CIH), characteristic to individuals who work in shift systems at high altitude, alternating high altitude working periods with resting periods at sea level This condition can be observed in the Chilean mining activities on the Andean Mountains, especially in copper extraction, since it is one of the largest copper producing countries in the world, with approximately 16 mining operations above 3000 m.a.s.l. By 2019, Chile held a total working force of 248,803 miners, including men and women, where 34.3% of the workers had 7 × 7 shifts (seven days of work, followed by seven days of rest at sea level) and a 30.3% of them had 4 × 4 shifts, in a schedule that last several years. 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 d iseases[4]
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