Differential Effects of Shear Forces and Pressure on Blood Vessel Metabolism and Function in a Perfusion Model

Abstract

Tissue engineering protocols commonly incorporate mechanical stimuli like pulsatile flow and luminal pressure to adapt the constructs to the biomechanical requirements of the target circulation. This study investigated the effects of shear forces and of luminal pressure on blood vessel metabolism and function using bovine veins as a model. Veins were perfused for four days in M199 at 40 ml/min. Shear forces were increased by adjusting the viscosity of the medium to that of blood. Some veins were additionally treated with luminal pressure. Control groups were either denuded or perfused with 60 ml/min to assess the influences of endothelium and of elevated flow rates, respectively. Physiological shear forces were sufficient to maintain endothelial integrity, unless superphysiological flow rates were applied. Reductive capacities were not affected by any of the perfusion conditions. Responses to the receptor-dependent vasoconstrictor noradrenalin were increased after perfusing with physiological shear forces and luminal pressure. This also induced a shift of the metabolism from glycolysis and lactate fermentation to the use of alternative substrates other than glucose. Mechanically denuded control vessels were prone to apoptosis and showed an altered metabolism as well. However, denuded vessels treated with luminal pressure also showed improved responses to vasoconstrictors compared to denuded controls. These results indicate that mechanical challenges are required to maintain endothelial integrity and to improve contractile function of vessels in perfusion systems. Metabolic patterns change with mechanical challenges, and care should be taken to provide sufficient amounts of substrates other than glucose for energy metabolism.