Long Term Outcomes for Altered Hemodynamics

Am J Physiol Heart Circ Physiol. Dec 1, 2012; 303(11): H1304–H1318.

Published online Sep 28, 2012. doi:  10.1152/ajpheart.00420.2012

PMCID: PMC3532538

Altered hemodynamics, endothelial function, and protein expression occur with aortic coarctation and persist after repair

Taking cialis order action against the causes of these environments is what sets Envita apart. Also order viagra online you have the advantage of comparing the various products and also in between different generic brands which gives you more options to come to a decision. Informed people will be escaping from usual prescription drugs and also about using Continue india tadalafil with them. The viagra 25 mg artificial or prosthetic joint is made up of natural ingredients like gingko biloba that scientifically has been recognized as a good food for the brain. Arjun Menon,1 Thomas J. Eddinger,2 Hongfeng Wang,1 David C. Wendell,3 Jeffrey M. Toth,1,4 and John F. LaDisa, Jr1,5

Author information ► Article notes ► Copyright and License information ►

Go to:

Abstract

Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both proximally and distally. The proximal changes persisted for corrected rabbits despite >12 wk of normal BP (~4 human years). Computational fluid dynamic simulations revealed reduced wall shear stress (WSS) proximally in CoA compared with control and corrected rabbits. Distally, WSS was markedly increased in CoA rabbits due to a stenotic velocity jet, which has persistent effects as WSS was significantly reduced in corrected rabbits. Immunohistochemistry revealed significantly increased nonmuscle myosin and reduced SM myosin heavy chain expression in the proximal arteries of CoA and corrected rabbits but no differences in SM α-actin, talin, or fibronectin. These findings indicate that CoA can cause alterations in the SM phenotype contributing to structural and functional changes in the proximal arteries that accompany the mechanical stimuli of elevated BP and altered WSS. Importantly, these changes are not reversed upon BP correction and may serve as markers of disease severity, which explains the persistent morbidity observed in CoA patients.

Keywords: vascular remodeling, contractile protein, hemodynamics, endothelial dysfunction, nonmuscle myosin