Effects of living at moderate altitude on pulmonary vascular function and exercise capacity in mice with sickle cell anaemia

摘要

Exposure to high altitude worsens symptoms and crises in patients with sickle cell disease (SCD). However, it remains unclear whether prolonged exposure to low barometric pressures exacerbates SCD aetiologies or impairs quality of life. We tested the hypothesis that, relative to wild-type (WT) mice, Berkley sickle cell mice (BERK-SS) residing at sea level, mild (1609m) and moderate (2438m) altitude would have a higher rate of haemolysis, impaired cardiac function and reduced exercise tolerance, and that the level of altitude would worsen these decrements. Following 3months of altitude exposure, right ventricular systolic pressure was measured (solid-state transducer). In addition, the adaptive balance between pulmonary vascular endothelial nitric oxide synthase and endothelin was assessed in lung tissue to determine differences in pulmonary vascular adaptation and the speed/duration relationship (critical speed) was used to evaluate treadmill exercise tolerance. At all altitudes, BERK-SS mice had a significantly lower percentage haemocrit and higher total bilirubin and free haemoglobin concentration (P0.05 for all). right ventricular systolic pressures in BERK-SS were higher than WT at moderate altitude and also compared to BERK-SS at sea level (P0.05, for both). Critical speed was significantly lower in BERK-SS at mild and moderate altitude (P0.05). BERK-SS demonstrated exacerbated SCD complications and reduced exercise capacity associated with an increase in altitude. These results suggest that exposure to mild and moderate altitude enhances the progression of SCD in BERK-SS mice compared to healthy WT cohorts and BERK-SS mice at sea level and provides crucial information for the clinical counselling of SCD patients.