In vitro system to study realistic pulsatile flow and stretch signaling in cultured vascular cells |
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Authors: | Peng X Recchia F A Byrne B J Wittstein I S Ziegelstein R C Kass D A |
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Institution: | Division of Cardiology, Departments of Medicine and Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-5500, USA. |
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Abstract: | We developed a novel real-timeservo-controlled perfusion system that exposes endothelial cells grownin nondistensible or distensible tubes to realistic pulse pressures andphasic shears at physiological mean pressures. A rate-controlled flowpump and linear servo-motor are controlled by digitalproportional-integral-derivative feedback that employspreviously digitized aortic pressure waves as a command signal. Theresulting pressure mirrors the recorded waveform and can be digitallymodified to yield any desired mean and pulse pressure amplitude,typically 0-150 mmHg at shears of 0.5-15 dyn/cm2.The system accurately reproduces the desired arterial pressure waveformand cogenerates physiological flow and shears by the interaction ofpressure with the tubing impedance. Rectangular glass capillary tubes1-mm inside diameter (ID)] are used for real-time fluorescentimaging studies (i.e., pHi, NO, Ca2+), whereassilicon distensible tubes (4-mm ID) are used for more chronic (i.e.,2-24 h) studies regarding signal transduction and geneexpression. The latter have an elastic modulus of12.4 · 106 dyn/cm2 similar to in vivovessels of this size and are studied with the use of a benchtop system.The new approach provides the first in vitro application of realisticmechanical pulsatile forces on vascular cells and should facilitatestudies of phasic shear and distension interaction and pulsatile signal transduction. |
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