Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension

• Published in: PloS one Vol. 8; no. 11; p. e78569
• Main Authors: Wang, Zhijie, Lakes, Roderic S, Golob, Mark, Eickhoff, Jens C, Chesler, Naomi C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2013; Public Library of Science (PLoS)
• Subjects: Angiogenesis Inhibitors - adverse effects; Animals; Antiangiogenics; Biomedical engineering; Blood Pressure; Chronic Disease; Collagen; Collagen - chemistry; Damping ratio; Dynamic mechanical properties; Elastic Modulus; Energy dissipation; Energy storage; Engineering; Extracellular matrix; Familial Primary Pulmonary Hypertension; Frequency dependence; Health aspects; Heart; Heart failure; Hypertension; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - pathology; Hypoxia; Hypoxia - complications; Hypoxia - pathology; Indoles - adverse effects; Male; Mechanical properties; Mechanical tests; Mice; Mice, Inbred C57BL; Mortality; Muscle contraction; Muscles; Myocytes, Smooth Muscle - chemistry; Myocytes, Smooth Muscle - pathology; Proteoglycans; Proteoglycans - chemistry; Pulmonary arteries; Pulmonary artery; Pulmonary hypertension; Pyrroles - adverse effects; Rodents; Smooth muscle; Stiffening; Stiffness; Storage modulus; Stress, Mechanical; Vascular Stiffness; Veins & arteries; Ventricle; Ventricular Dysfunction, Right - chemically induced; Ventricular Dysfunction, Right - complications; Ventricular Dysfunction, Right - pathology; Viscoelasticity; Viscosity; United States > US; Wisconsin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078569

Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation.