Liver failure is associated with high morbidity and mortality without transplantation. There are two types of device for temporary support: artificial and bioartificial livers. Artificial livers essentially use non-living components to remove the toxins accumulated during liver failure. Bioartificial livers have bioreactors containing hepatocytes to provide both biotransformation and synthetic liver functions. We review here the operating principles, chemical effects, clinical effects and complications of both types, with specific attention paid to bioartificial systems. Several artificial support systems have FDA marketing authorisation or are CE labelled, but the improvement they provide in terms of patient clinical outcome has not yet been fully demonstrated. At present, different bioartifical systems are being investigated clinically on the basis of their promises and capacity to provide and replace most liver functions. However, important issues such as cost, cell availability, maintenance of cell viability and functionality throughout treatment, and regulatory issues, as well as difficult challenges, including implementing cell-housing devices at the patient's bedside on an emergency basis, have delayed their appearance in intensive care units and on the market. Bioreactors are, nevertheless, when combined with artificial components, a pragmatic approach for future treatment of liver failure.
-Hematocrit (Hct) of awake hamsters and CD-1 mice was acutely increased by isovolemic exchange transfusion of packed red blood cells (RBCs) to assess the relation between Hct and blood pressure. Increasing Hct 7-13% of baseline decreased mean arterial blood pressure (MAP) by 13 mmHg. Increasing Hct above 19% reversed this trend and caused MAP to rise above baseline. This relationship is described by a parabolic function (R 2 ϭ 0.57 and P Ͻ 0.05). Hamsters pretreated with the nitric oxide (NO) synthase (NOS) inhibitor N -nitro-L-arginine methyl ester (L-NAME) and endothelial NOS-deficient mice showed no change in MAP when Hct was increased by Ͻ19%. Nitrate/nitrite plasma levels of Hct-augmented hamsters increased relative to control and L-NAME treated animals. The blood pressure effect was stable 2 h after exchange transfusion. These findings suggest that increasing Hct increases blood viscosity, shear stress, and NO production, leading to vasodilation and mild hypotension. This was corroborated by measuring A1 arteriolar diameters (55.0 Ϯ 21.5 m) and blood flow in the hamster window chamber preparation, which showed statistically significant increased vessel diameter (1.04 Ϯ 0.1 relative to baseline) and microcirculatory blood flow (1.39 Ϯ 0.68 relative to baseline) after exchange transfusion with packed RBCs. Larger increases of Hct (Ͼ19% of baseline) led blood viscosity to increase Ͼ50%, overwhelming the NO effect through a significant viscosity-dependent increase in vascular resistance, causing MAP to rise above baseline values. nitric oxide; shear stress; vascular resistance; hypertension IT IS A GENERAL MEDICAL and clinical perception that an increase in blood viscosity may lead to short-and long-term negative physiological conditions, and there appears to be universal agreement that increased blood viscosity is a factor in hypertension. Lowering blood viscosity, however, is not advocated as a means for controlling hypertension with the exception of erythrocytosis, substantial Hct increases consequent to adaptation to high altitudes, and cardiovascular impairment in premature infants. These conditions represent extremes of an increase in blood viscosity and clearly must be corrected by lowering Hct, because the extreme excess of red blood cells (RBCs) is superfluous in providing adequate oxygen-carrying capacity and is in fact a hindrance to blood flow and therefore oxygen delivery.Clinical studies (14, 37) report a significant relationship between hypertension and high Hct levels. Hypertensive patients have higher Hct values than normotensive control individuals (23). Patients suffering from polycythemia vera or other erythrocytoses present with pathologically high Hcts leading to hypertension, thromboembolism, and other severe clinical complications (2, 15). There is evidence, however, that individuals, such as Peruvian miners, survive with Hct levels of 75-91% (18), suggesting the existence of an adaptive mechanism.Endothelial cells play a key role in the regulation of blood pressure and blood flow beca...
Liver-assist devices have been developed in the last few decades to support patients with liver failure on the road to recovery or transplantation. Fluidised bed bio-artificial livers -where liver cells are encapsulated within alginate beads -appear to be a valuable alternative to hollow fibre devices for improving mass transfers and enhancing treatment efficacy. This approach nevertheless deserves optimization in terms of bead production. The aim of this study was to investigate the impact of alginate type and of two bead diameters (1000 μm and 600 μm) on mass transfers within beads and on the biological functions of encapsulated C3A cells.After assessing the effect of the encapsulation process on bead quality, we investigated cell viability and metabolic activities (ammonia, albumin, α-foetoprotein synthesis and glucose consumption). They were successfully maintained over 48 h within fluidised bed bioreactors, independently of alginate type and bead diameter. Mass transfers were not significantly influenced by the latter parameters. Finally, suggestions are made for improving the entrapment process as a means of enhancing the treatment efficiency of the fluidised bed bioartificial liver.
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