Persistent vascular collagen accumulation alters hemodynamic recovery from chronic hypoxia

JOURNAL OF BIOMECHANICS

卷:45

Article

Tabima, Diana M.¹  Roldan-Alzate, Alejandro¹  Wang, Zhijie¹  Hacker, Timothy A.²  Molthen, Robert C.³  Chesler, Naomi C.^1,2 

[1] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53706 USA

[2] Univ Wisconsin, Dept Med, Madison, WI 53706 USA

[3] Med Coll Wisconsin, Dept Med PCC, Milwaukee, WI 53201 USA

关键词: Pulmonary hemodynamics;    Pulmonary hypertension;    Pulmonary vascular impedance;    Pulmonary artery stiffness;    Collagen;   

DOI  :  10.1016/j.jbiomech.2011.11.020

来源: Elsevier

【 摘 要 】

Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z(o)), characteristic impedance (Z(c)), pulse wave velocity (PWV) and index of global wave reflections (P-b/P-f), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1(R/R)) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1(+/+)) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z(o) (mPAP/CO) increased by similar to 100% in both genotypes (p < 0.05). Contrary to our expectations, Z(c), PWV and Pb/Pf did not change. However, with recovery. Z(c) and PWV decreased in the Col1a1(+/+) mice and remained unchanged in the Col1a1(R/R) mice. Z(o) decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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