A New Computerized Biomechanical Perfusion Model for ex vivo Study of Fluid Mechanical Forces in Intact Conduit Vessels

Abstract

We have developed a new computerized biomechanical ex vivo perfusion system for intact conduit vessels in which a wide range of combinations of intraluminal pressure, fluid flow and shear stress could be set and maintained at target levels in mammalian conduit vessels under controlled metabolic conditions. Mean wall shear stress is calculated using the formula:τ = 1/2 * (ΔP/L)^3/4 * (8ηQ/Π)^1/4.Accuracy of the wall shear stress calculation was validated by ultrasonographic imaging of the vessel radius. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were challenged by generating a wide range of vascular resistance in artificial vessels and by pharmacologically induced changes in vascular tone in intact human vessels. Despite rapid changes in vessel resistance, shear stress and pressure, or flow and pressure were maintained well at target levels. Shear- and pressure-stimulated production of the vasodilator prostaglandin E₂ (PGE₂) was used to validate the biological relevance of the model. PGE₂ release was significantly more stimulated by high (25 dyn/cm²) compared to low (<4 dyn/cm²) shear (ANOVA, p = 0.012). High compared to low intraluminal pressure depressed the production of PGE₂ (ANOVA, p = 0.019). In summary, the computerized perfusion model appears to offer new possibilities of investigating the complex interplay between fluid mechanics and the vascular wall.

Elevated Intraluminal Pressure Inhibits Vascular Tissue Plasminogen Activator Secretion and Downregulates Its Gene Expression

“…7 Briefly, fresh human umbilical veins are perfused antegradely with Tyrode's saline solution containing (in mmol/L) NaCl 146, KCl 6, CaCl 2 3, MgCl 2 0.5, KH 2 PO 4 0.3, NaHCO 3 20, and glucose 5.6, pH 7.4, in 2 parallel gravity-fed circuits ( Figure 1). Medium is continuously pumped to an upper reservoir, of which the height is regulated with a computercontrolled motor unit.…”

“…However, the investigation of this hypothesis is complicated by the fact that in an intact vessel, changes in perfusion pressure invariably lead to changes in wall shear stress, which by itself may increase tPA gene expression. 4 -6 To overcome this problem, we used a new computerized biomechanical ex vivo perfusion model that we developed, 7 in which intraluminal pressure and shear stress can be controlled independently of each other. Our results show for the first time that elevated intraluminal pressure per se inhibits tPA secretion from endothelial cells and downregulates its gene expression in intact human conduit vessels.…”

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 [256,262,265,270,[284][285][286]. A system described by Bergh et al (2005) should be noted due to its robust capabilities [262].…”

“…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.

“…Systems are typically driven via peristaltic pumps [75][76][77][78] in order to mimic various pulsatile flow waveforms. 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 .…”