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Pulmonary Arterial Structure and Mechanics in the Progression of Pulmonary Arterial Hypertension
Author(s) -
ValdezJasso Daniela,
Pursell Erica,
VélezRendón Daniela
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1015.31
Subject(s) - medicine , pulmonary artery , ex vivo , pulmonary hypertension , saline , hemodynamics , masson's trichrome stain , cardiology , arterial stiffness , in vivo , vascular resistance , blood pressure , pathology , fibrosis , biology , microbiology and biotechnology
Pulmonary Arterial Hypertension (PAH) is characterized by high blood pressure in the pulmonary system. This disease aggressively remodels the pulmonary vasculature as it progresses. The goal of this work is to characterize the structural changes at different stages of PAH. We hypothesize that the changes at the organ (hemodynamic) and tissue (mechanical) level have different rates of manifestation, and a better understanding of this progression can improve our understanding of PAH. Sprague‐Dawley rats were divided into placebo (PL=17 injected with saline) and monocrotaline‐treated group (MCT=8). From mild (week 1) and advanced (week 4) post‐injection, rats underwent open chest surgeries to measure pulmonary arterial pressure and volumetric flow. Post in vivo measurements, the left and right pulmonary artery (LPA and RPA) segments were harvested and cannulated. The stiffness of the vessels was determined through ex vivo mechanical testing, while the fiber orientation was quantified by multiphoton microscopy (MPM) imaging. Collagen content was quantified using Masson's Trichrome histological staining. Mean pulmonary arterial pressure for PL to advanced PAH increased significantly from 24.1±4.9 to 44.4±6.3 mmHg, and mean flow decreased from 40.4±11 to 28.9±7 ml/min. Total vascular resistance and wave reflection statistically significantly increased in week 4 of MCT. Vessels became stiffer from baseline to advanced state for both vessel types, but it was statistically significantly larger in the RPA. MPM imaging revealed RPA collagen fibers to become uncrimped and highly aligned to the 45 degree angle, whereas the LPA fiber distribution remained nearly constant. Collagen content continuously increased from PL to advanced PAH. Specifically, the LPA went from 50%–59% whereas the RPA collagen content went from 53% to 68%. Hemodynamic study shows an increase in resistive properties and decrease in dampening effects of the pulmonary vasculature. This leads to less compliant vessels, compromising the buffering of incoming pressure and flow, and heart adaptation in order to deliver the same amount of blood to the pulmonary system. Mechanically, the vessels adjusted to elevated pressure during the progression of PAH as indicated by an increase of Young's Modulus (stiffness), collagen content, and change in crimped configuration of collagen. However, the RPA remodels significantly more than the LPA based on its larger stiffness values, higher increase in collagen content, and reorganization of fibers. Support or Funding Information American Heart Association Scientist Development Grant 16SDG29670010Structural organization of the pulmonary artery in a normotensive (left panel) and hypertensive (right panel). Images from multiphoton microscope show collagen fibers going from randomly organized to highly aligned in the advanced stage of pulmonary arterial hypertension. Collagen content also increases via histological slides.