RESUMEN
Perfluorocarbons are now being used as oxygen carriers in clinical settings. Because these chemicals may have a role as a blood substitute, in organ preservation, and in the management of respiratory failure, we have reviewed some of the research leading to these applications.
Asunto(s)
Fluorocarburos/uso terapéutico , Oxígeno/farmacocinética , Transporte Biológico , Sustitutos Sanguíneos/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Fluorocarburos/efectos adversos , Humanos , Sistema Mononuclear Fagocítico/efectos de los fármacos , RespiraciónRESUMEN
A mathematical model has been developed to investigate previously obtained experimental findings relating to the activation of factor X by surface-bound tissue factor--factor VIIa (TF:VIIa) in a tubular flow reactor. In those experiments, factor X was perfused through a microcapillary tube over a range of flow (shear) conditions and the activated product, factor Xa, was measured at the outlet of the tube using a chromogenic assay. In the present study, the steady-state convection-diffusion equation with Michaelis-Menten kinetics used to describe the reaction at the wall was numerically integrated using an implicit method based on linear systems of ordinary differential equations. The results from the numerical analysis indicated that shear rate directly affects both Km and Vmax. Values of Km decreased from 151 to 16 nM as the shear rate increased from 25 to 2400 sec-1. Additionally, there was a twofold increase in Vmax from 1.4 to 3.0 pmol/cm2/min as the shear rate increased from 25 to 300 sec-1. These findings are in contrast with classical enzyme behavior and imply a direct effect of fluid flow on the kinetics of factor X activation.
Asunto(s)
Factor VIIa/metabolismo , Factor X/metabolismo , Modelos Biológicos , Tromboplastina/metabolismo , Cinética , ReologíaRESUMEN
The purpose of the present study was to examine the role of antithrombotic agents in the activation of Factor X in the presence of the Tissue Factor-Factor VIIa (TF-VIIa) complex in a continuous-flow reactor. Tissue Factor immobilized in a phospholipid bilayer on the inner surface of a capillary tube (internal diameter = 0.27 mm) was exposed to a perfusate containing Factors VIIa and X flowing at a flow rate of 12.7 microliters/min, corresponding to a wall shear rate of 100 s-1. Factor Xa (the activated form of Factor X) in the effluent was determined by a chromogenic assay. The effectiveness of two platelet aggregation inhibitors, alpha,alpha'-bis-[3-(N,N-diethylcarbamoyl)piperidino-p-xylene dihydrobromide (A-1) and alpha,alpha'-bis-[3-N-benzyl-N-methylcarbamoyl)piperidino]-p-xylen e dihydrobromide (A-4) in inhibiting Factor X activation is reported here. The results suggest that the Tissue Factor pathway, mediated through TF-VIIa complex, produces significantly lower levels of Factor Xa in the presence of compounds A-1 and A-4. On the basis of these findings, it appears that the anticoagulation action of these compounds reinforces their platelet aggregation-inhibitory properties. These carbamoylpiperidines (nipecotamides) therefore appear to be useful antithrombotic agents.
Asunto(s)
Factor VIIa/química , Fibrinolíticos/química , Ácidos Nipecóticos/química , Inhibidores de Agregación Plaquetaria/química , Tromboplastina/química , Estudios de Evaluación como Asunto , Factor X/química , Estructura MolecularRESUMEN
Previous studies have shown the tendency for frictional heating to occur during articulation of total hip systems in vitro under simulated hip loading conditions. The magnitude of this heating is sufficient to accelerate wear, creep, and oxidation degradation of the UHMWPE bearing surface. It was shown that ceramic articulating systems generate less frictional heating than polished cobalt alloy against UHMWPE. This frictional heating is expected to occur primarily for younger, heavier, and more active patients. Thus, long-term performance of the articulating hip system in these patients may not be that predicted from current, body-temperature wear, creep, and degradation studies. Although the tendency to generate frictional heat has been observed only during in vitro simulated hip loading, a heat transfer analysis of this phenomenon is presented to evaluate the ability of the hip joint to dissipate such heating in vivo. Additional experiments were performed using controlled resistance heaters inside a cobalt femoral head to verify the calculated levels of frictional heat and to assess the heat dissipation under simulated in vivo conditions. The effect of blood perfusion on the effective thermal conductivity of the joint capsule is also discussed. The present study describes and analyzes the various heat dissipation mechanisms present both in vitro and in vivo during articulation of metal and ceramic hip systems. From these tests and analyses, it is concluded that frictional heating in the reconstructed hip cannot be effectively removed, and that degredative elevated temperature processes can be expected to occur in vivo to both the UHMWPE and adjacent tissue under extended periods of excessive patient activity. This is particularly true for metal cobalt alloy femoral heads articulating on UHMWPE versus ceramic heads which generate significantly lower levels of heat.
Asunto(s)
Prótesis de Cadera , Calor , Aleaciones , Óxido de Aluminio , Materiales Biocompatibles , Cerámica , HumanosRESUMEN
In Part I, (J.A. Davidson and G. Schwartz, "Wear, creep, and frictional heating of femoral implant articulating surfaces and the effect on long-term performance--Part I, A review," J. Biomed. Mater. Res., 21, 000-000 (1987) it was shown that lubrication of the artificial hip joint was complex and that long-term performance is governed by the combined wear, creep, and to a lesser extent, oxidation degradation of the articulating materials. Importantly, it was shown that a tendency for heating exists during articulation in the hip joint and that elevated temperatures can increase the wear, creep, and oxidation degradation rate of UHMWPE. The present study was performed to examine closely the propensity to generate heat during articulation in a hip joint simulator. The systems investigated were polished Co-Cr-Mo alloy articulating against UHMWPE, polished alumina ceramic against UHMWPE, and polished alumina against itself. Frictional torque was also evaluated for each system at various levels of applied loads. A walking load history was used in both the frictional heating and torque tests. The majority of tests were performed with 5 mL of water lubricant. However, the effect of various concentrations of hyaluronic acid was also evaluated. Results showed frictional heating to occur in all three systems, reaching an equilibrium after roughly 30 min articulation time. Ceramic systems showed reduced levels of heating compared to the cobalt alloy-UHMWPE system. The level of frictional torque for each system ranked similar to their respective tendencies to generate heat. Hyaluronic acid had little effect, while dry conditions and the presence of small quantities of bone cement powder in water lubricant significantly increased frictional torque.