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Am J Physiol Heart Circ Physiol 287: H1561-H1569, 2004. First published May 20, 2004; doi:10.1152/ajpheart.00081.2004
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Measuring hemodynamic changes during mammalian development

E.A.V. Jones,1 M.H. Baron,3 S.E. Fraser,2 and M.E. Dickinson2

1Department of Chemical Engineering and 2Biological Imaging Center, Department of Biology, California Institute of Technology, Pasadena, California 91125; and 3Mount Sinai School of Medicine, New York, New York 10029

Submitted 2 February 2004 ; accepted in final form 17 May 2004

The pathogenesis of many congenital cardiovascular diseases involves abnormal flow within the embryonic vasculature that results either from malformations of the heart or defects in the vasculature itself. Extensive genetic and genomic analysis in mice has led to the identification of an array of mutations that result in cardiovascular defects during embryogenesis. Many of these mutations cause secondary effects within the vasculature that are thought to arise because of altered fluid dynamics. Presumably, cardiac defects disturb or reduce flow and thereby lead to the disruption of the mechanical signals necessary for proper vascular development. Unfortunately, a precise understanding of how flow disruptions lead to secondary vasculature defects has been hampered by the inadequacy of existing analytical tools. Here, we used a fast line-scanning technique for the quantitative analysis of hemodynamics during early organogenesis in mouse embryos, and we present a model system for studying cellular responses during the formation and remodeling of the mammalian cardiovascular system. Flow velocity profiles can be measured as soon as a heart begins to beat even in newly formed vessels. These studies establish a link between the pattern of blood flow within the vasculature and the stage of heart development and also enable analysis of the influence of mechanical forces during development.

confocal microscopy; line scanning; yolk sac; green fluorescent protein



Address for reprint requests and other correspondence: M. E. Dickinson, Biological Imaging Center, Beckman Institute, MC139-74, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125 (E-mail: maryd{at}gg.caltech.edu)




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