In vitro system to study realistic pulsatile flow and stretch signaling incultured vascular cells

We developed a novel realtime servo-controlled perfusion system that expose s endothelial cells grown in nondistensible or distensible tubes to realist ic pulse pressures and phasic shears at physiological mean pressures. A rat e-controlled flow pump and linear servo-motor are controlled by digital pro portional-integral-derivative feedback that employs previously digitized ao rtic pressure waves as a command signal. The resulting pressure mirrors the recorded waveform and can be digitally modified to yield any desired mean and pulse pressure amplitude, typically 0-150 mmHg at shears of 0.5-15 dyn/ cm(2). The system accurately reproduces the desired arterial pressure wavef orm and cogenerates physiological flow and shears by the interaction of pre ssure with the tubing impedance. Rectangular glass capillary tubes [1-mm in side diameter (ID)] are used for real-time fluorescent imaging studies (i.e ., pH(i), NO, Ca2+), whereas silicon distensible tubes (4-mm ID) are used f or more chronic (i.e., 2-24 h) studies regarding signal transduction and ge ne expression. The latter have an elastic modulus of 12.4.10(6) dyn/cm(2) s imilar to in vivo vessels of this size and are studied with the use of a be nchtop system. The new approach provides the first in vitro application of realistic mechanical pulsatile forces on vascular cells and should facilita te studies of phasic shear and distension interaction and pulsatile signal transduction.