Abstract
Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals/group), animals underwent transthoracic echocardiography and PA catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis was performed. Artery rings obtained from the pulmonary trunk, right and left PAs, and aorta were subjected to a tensile test to rupture. Collagen and elastin content were determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus, and wall viscosity increased, whereas the elastin-to-collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased, and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in hypoxic and normoxic animals with negligible wave reflection. In contrast, the aortic maximal elastic modulus remained unchanged, whereas wall viscosity decreased. In conclusion, there was no evidence of altered arterial wave propagation in proximal PAs of hypoxic rats while the extracellular matrix protein composition was altered and collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.NEW & NOTEWORTHY In rats exposed to chronic hypoxia, we have shown that pulse wave velocity in the proximal pulmonary arteries increased and pressure dependence of the pulse wave velocity was steeper in vivo than ex vivo leading to a more prominent increase in vivo.
Highlights
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction, vascular remodeling, inflammation, and thrombosis [8], resulting in increased pulmonary vascular resistance (PVR), vessel stiffening, and vascular impedance mismatch, leading to the generation of large reflected waves [30, 46, 57]
The effect of hypoxia was evidenced by the lower weight gain, shorter tibia length, higher hematocrit, and higher Fulton’s index (RV weight/left ventricle ϩ septum weight) in the hypoxic group (Table 2)
Transthoracic echocardiography was performed on 8 normoxic animals and 10 hypoxic animals; right heart catheterization was performed on normoxic animals and hypoxic animals
Summary
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction, vascular remodeling, inflammation, and thrombosis [8], resulting in increased pulmonary vascular resistance (PVR), vessel stiffening, and vascular impedance mismatch, leading to the generation of large reflected waves [30, 46, 57]. PAH-specific drugs, such as phosphodiesterase-5 inhibitors, prostanoid analogs, and endothelin receptor antagonists, mainly target the pulmonary arterioles and aim to decrease PVR, i.e., the steady flow component of RV afterload [52]. It has become apparent in recent years that arterial stiffness is independently associated with RV dysfunction [55] and is a strong independent predictor of mortality in PAH [34]. Whether the mechanical properties ex vivo match the in vivo conditions and whether hypoxia affects the mechanical properties of the aorta have not been well elucidated
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