HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H3006    most recent 01012.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Ghorishi, Z. Articles by Eldridge, M. W. Search for Related Content PubMed PubMed Citation Articles by Ghorishi, Z. Articles by Eldridge, M. W.

Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow

¹Neonatology Division, Department of Pediatrics, University of California, Davis and ²Department of Pediatrics, University of California, San Francisco, California; and ³Department of Pediatrics, Population Health Sciences and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin

Submitted 14 September 2006 ; accepted in final form 12 February 2007

Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d₀ and daughters d₁ d₂ with < 2 in (d₁/d₀) + (d₂/d₀) and area ratio < 1 in = (d₁²+ d₂²)/ d₀²] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D₀ delineates hemodynamic reactivity. Fetus and Control twin D₀ differed: fetus D₀ = 1.72, a high-resistance/shear stress amplifying condition; control twin D₀ = 2.02, an area-preserving transport configuration. The Shunt twin (D₀ = 1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

pulmonary arterial morphometry; branching complexity; fractals