A New Biomechanical Perfusion System for ex vivo Study of Small Biological Intact Vessels

Abstract

The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.

In Situ Bioengineering of Arterial Vein Grafts

“…Although several EVPSs with pulsatile pressure and flow generating capabilities have previously been described, none to date have shown the ability to accurately mimic both physiologic arterial pressure and flowrate waveforms [256,262,265,[284][285][286]. The system recently developed by Bergh et al (2005) reported robust capabilities in that they were able to control pressure or flowrate, and they validated their control algorithm with disturbances [262]. However, the higher frequency harmonic content of neither the physiologic pressure nor the flowrate signals could be generated using the components of their system.…”

“…Although several EVPSs with pulsatile pressure and flow generating capabilities have previously been described, none to date have shown the ability to accurately mimic both physiologic arterial pressure and flowrate waveforms [256,262,265,270,[284][285][286]. A system described by Bergh et al (2005) should be noted due to its robust capabilities [262].…”

“…A system described by Bergh et al (2005) should be noted due to its robust capabilities [262]. They reported the ability to precisely control pressure, flowrate, pH, pO 2 and temperature within their EVPS, and validated their control algorithm with prescribed perturbations to systemic conditions.…”

“…Other systems have been reported which were designed without the ability to accurately simulate the higher frequency content of the physiologic arterial pressure or flowrate waveforms. They instead were designed to generate certain desired static [256][257][258][259][260] or oscillatory [81,142,[261][262][263][264][265][266][267][268][269][270] signals for the purpose of estimating the biomechanical properties of blood vessel segments.…”

Development of a physiologic ex vivo vessel perfusion system.

“…They typically utilize precise pressure, flow, and gas exchange control to measure a variety of endpoints, such as fluid mechanical forces 75,76 and biological marker expression [78][79][80][81][82] . Some even have unique abilities like the capacity for longitudinal stretch 77,79 or the measurement of vessel diameter 80,83 . Like mock circulatory loops, these systems are highly adaptable and can be modified to support a variety of research needs.…”