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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep

¹Laboratorio de Fisiología y Fisiopatología del Desarrollo, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago; ²Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; ³International Center for Andean Studies, Universidad de Chile, Santiago-Arica-Putre, Chile; ⁴Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California; ⁵Facultad de Medicina, Pontificia Universidad Católica Madre y Maestra, Santiago de los Caballeros, República Dominicana; ⁶Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; ⁷Department of Pediatrics, Academic Hospital Maastricht, Maastricht, The Netherlands; ⁸Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, United Kingdom; and ⁹Universidad de Tarapacá and Centro de Investigaciones del Hombre en el Desierto, Arica, Chile

Submitted 29 December 2006 ; accepted in final form 10 February 2007

Perinatal exposure to chronic hypoxia induces sustained pulmonary hypertension and structural and functional changes in both pulmonary and systemic vascular beds. The aim of this study was to analyze consequences of high-altitude chronic hypoxia during gestation and early after birth in pulmonary and femoral vascular responses in newborn sheep. Lowland (LLNB; 580 m) and highland (HLNB; 3,600 m) newborn lambs were cathetherized under general anesthesia and submitted to acute sustained or stepwise hypoxic episodes. Contractile and dilator responses of isolated pulmonary and femoral small arteries were analyzed in a wire myograph. Under basal conditions, HLNB had a higher pulmonary arterial pressure (PAP; 20.2 ± 2.4 vs. 13.6 ± 0.5 mmHg, P < 0.05) and cardiac output (342 ± 23 vs. 279 ± 13 ml·min^–1·kg^–1, P < 0.05) compared with LLNB. In small pulmonary arteries, HLNB showed greater contractile capacity and higher sensitivity to nitric oxide. In small femoral arteries, HLNB had lower maximal contraction than LLNB with higher maximal response and sensitivity to noradrenaline and phenylephrine. In acute superimposed hypoxia, HLNB reached higher PAP and femoral vascular resistance than LLNB. Graded hypoxia showed that average PAP was always higher in HLNB compared with LLNB at any PO₂. Newborn lambs from pregnancies at high altitude have stronger pulmonary vascular responses to acute hypoxia associated with higher arterial contractile status. In addition, systemic vascular response to acute hypoxia is increased in high-altitude newborns, associated with higher arterial adrenergic responses. These responses determined in intrauterine life and early after birth could be adaptive to chronic hypoxia in the Andean altiplano.

hypoxemia; pulmonary hypertension; vascular reactivity; neonatal lamb; highlands

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