Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics

Abstract

We tested the effect of acetazolamide on blood mechanical properties and pulmonary vascular resistance (PVR) during chronic hypoxia.Six groups of rats were either treated or not treated with acetazolamide (curative: treated after 10 days of hypoxic exposure; preventive: treated before hypoxic exposure with 40 mg?kg) and either exposed or not exposed to 3 weeks of hypoxia (at altitude .5,500 m). They were then used to assess the role of acetazolamide on pulmonary artery pressure, cardiac output, blood volume, haematological and haemorheological parameters.Chronic hypoxia increased haematocrit, blood viscosity and PVR, and decreased cardiac output. Acetazolamide treatment in hypoxic rats decreased haematocrit (curative by -10% and preventive by -11%), PVR (curative by -36% and preventive by -49%) and right ventricular hypertrophy (preventive -20%), and increased cardiac output (curative by +60% and preventive by +115%). Blood viscosity was significantly decreased after curative acetazolamide treatment (-16%) and was correlated with PVR (r50.87, p,0.05), suggesting that blood viscosity could influence pulmonary haemodynamics. The fall in pulmonary vascular hindrance (curative by -27% and preventive by -45%) after treatment suggests that acetazolamide could decrease pulmonary vessels remodelling under chronic hypoxia.The effect of acetazolamide is multifactorial by acting on erythropoiesis, pulmonary circulation, haemorheological properties and cardiac output, and could represent a pertinent treatment of chronic mountain sickness.

Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects

“…In the pulmonary circulation, hyperviscosity can have similarly detrimental effects. In a murine model of chronic mountain sickness, a disorder characterized by hypoxia-induced polycythemia and arterial desaturation, chronic hypoxia led to an increase in PVR which was both preventable and reversible via reduction in blood viscosity with acetazolamide [20]. Small studies in humans also suggest that the adverse hemodynamic effects of hyperviscosity are reversible, at least in the short term.…”

Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease

“…Each of these hemorheological parameters may affect the pulmonary vasculature. In animal models, increased blood viscosity and reduced RBC deformability have been shown to increase pulmonary vascular resistance, 9,26 and impaired RBC aggregation properties were demonstrated to impact microcirculation. 10 Multivariate analysis demonstrated that the RBC disaggregation threshold was the only parameter associated with the occurrence of ACS in SCC children.…”

“…6,7 Abnormal hemorheology may severely impact blood flow 8 as increased blood viscosity can raise vascular resistance both at the systemic and pulmonary levels. 9 Blood viscosity is modulated by the hematocrit, which can be very low in SCD due to hemolysis, and by the rheological properties of red blood cells (RBC), which are markedly altered in SCD by the presence of sickle hemoglobin, HbS. In addition, although poorly studied in SCD, 7 RBC aggregation may modulate blood flow in smaller blood vessels because increased RBC aggregation causes an accumulation of RBC in the central zone of flow (axial migration), resulting in a cell-poor layer near the vessel wall, and leading to decreased hematocrit of marginal blood streams (i.e.…”

Right Ventricle and High Altitude

“…The fall in pulmonary vascular hindrance (curative by −27 % and preventive by −45 %) suggests that Acz could decrease pulmonary vessels remodelling under chronic hypoxia. The effect of Acz appears multifactorial, acting on erythropoiesis, pulmonary circulation, hemorheological properties and cardiac output [ 45 ].…”