Aspectos técnicos de los dispositivos de perfusión de órgano aislado

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Abstract

Un aspecto de gran importancia en el campo de los trasplantes es el mantenimiento y preservación del órgano durante la fase isquémica. La sensibilidad del órgano a ésta y la posible lesión inducida durante la extracción, preservación y transporte, siguen siendo una de las principales causas de fracaso del injerto. La perfusión artificial de órganos ha sido objetivo de investigación durante más de 100 años. En la segunda mitad del siglo XX estas técnicas han sido aplicadas a la preservación experimental y clínica, con el fin de alargar el tiempo de almacenamiento efectivo (aquél que permite una función correcta y precoz tras el trasplante del órgano preservado). La meta primaria de la preservación de cualquier órgano es el mantenimiento de la integridad de todos los sistemas celulares, de tal manera que la posibilidad de lesión que lleve a la disfunción del injerto sea mínima.

Translated abstract

An aspect of capital importance in the transplant field is the maintainance and preservation of organs during the ischemic phase. Organ susceptibility and injuries secondary to ischemia, organ procurement and transportation are still nowadays one of the main causes for organ failure. Effective artificial organ perfusion has remained a main goal for researchers in this field for more than 100 years. In the second half of the XXth century these techniques have been applied to experimental and clinical organ preservation, with the aim of extending the period of an effective storage (which guarantees an early and good function after the transplant). Primary goal of any organ preservation is to maintain integrity in every cell system in order to minimize those injuries which produces graft dysfunction.

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Most cited references 31

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THE CULTURE OF WHOLE ORGANS

C. Lindbergh, A. Carrel (1935)

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Important components of the UW solution.

J Southard, T. M. van Gulik, M Ametani … (1990)

The UW solution for preservation of the liver, kidney, and pancreas contains a number of components, and the importance of each of these has not been fully resolved. In the studies reported here the importance of glutathione and adenosine is demonstrated in isolated cell models (rabbit renal tubules and rat liver hepatocytes) of hypothermic preservation and reperfusion and in dog renal transplantation. Glutathione in the UW solution is necessary for the preservation of the capability of the cell to regenerate ATP and maintain membrane integrity. Adenosine in the UW solution provides the preserved cell with substrates for the regeneration of ATP during the reperfusion period following cold storage. The omission of GHS from the UW solution results in poorer renal function in the 48 hr dog kidney preservation-transplant model. The role of other components of the UW solution is discussed including lactobionic acid; other impermeants; and the colloid, hydroxyethyl starch. It is concluded that the development of improved preservation solutions will require a more detailed understanding of the mechanism of injury due to cold storage and, once obtained, solutions more complex than the UW solution may be required for improved long-term storage of organs.

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The secretion of urine as studied on the isolated kidney

(1925)

Broadly speaking, there are two main avenues of approach in the attempt to unravel the complicated processes which determine the function of any individual organ. On the one hand, we may study its reaction in the intact animal to comparatively small environmental changes—a method of inestimable value, since it is one which may readily be applied to man ; on the other hand, we may remove the organ and study its reaction under grossly artificial conditions. In the former case, we sacrifice simplicity and full control to a close approximation to normality in environment ; in the latter case, we sacrifice normality in environment in order to obtain greater simplicity and a higher degree of experimental control. The former may be referred to as the analytic method of experimentation, the latter as the synthetic. On the one hand, we attempt to dissociate the medley of influences which share in determining the normal function of the organ, and to relegate to each its particular office in maintaining this normality ; on the other hand, we attempt to associate these influences in such a degree and in such a manner as to bring the isolated organ back to an environment and function comparable to the normal. We have used the latter method in an attempt to throw more light on the mechanism of urinary secretion in mammals. In order that the mammalian kidney may be kept alive in the isolated state, it is obvious from a consideration of its relatively enormous oxygen consumption—a consumption per gram per minute which may exceed that of the heart(10) (68)—that an efficient means of supplying this want must be at hand. Perfusion experiments such as those of Ludwig(1) in which a dog’s kidney was perfused with a solution containing 3 per cent. gum and 1 per cent. NaCI, can only hope to throw some light on the mechanical conditions obtaining in the dead organ. In 1890, Jacoby(2) perfused the isolated kidney of the dog with defibrinated blood by means of a pump and arterialised the blood by means of a current of air. With v. Sobieranski(3) he succeeded in obtaining a very slow urine flow by this means, but the fluid secreted invariably contained protein in considerable amounts. Three years later an improvement(4) in the form of apparatus was introduced in that an artificial pulmonary circulation was maintained by means of a second pump, the arterialised blood being then sent to the kidney as before. This improvement in technique, however, failed to give results of any promise. Similarly, Pfaff and Vejux Tyrode, (5) perfusing the dog’s kidney with defibrinated blood, invariably obtained blood and protein in the fluid issuing from the ureter. They claim to have shown that this untoward result was due to the toxic action of defibrinated blood. On defibrinating an animal the urine simultaneously secreted contained blood and protein, but this rapidly disappeared on removing the defibrinated blood, and replacing it with normal blood from another dog by bleeding this animal directly into the other’s venous system. Hirudin was tried and gave better results, but the experiments were not continued. The experiments of Sollmann(6) were performed with dog’s kidneys in the dead or dying condition. These were perfused with saline or highly diluted defibrinated blood in an attempt to study the mechanics of the organ. In 1903, Brodie(7) described an apparatus for the perfusion of isolated organs with oxygenated and defibrinated blood. He noticed, as had Pfaff and Vejux Tyrode, that vasoconstriction quickly set in under the conditions of experiment, but that(8) this could be overcome by the addition of chloral or amyl nitrite to the blood. A urine flow up to 16 c. c. per 15 minutes was obtained. Again, Hooker, (9) in a study of the influence of pulse pressure upon renal function, perfused dog’s kidneys by means of a pump with defibrinated blood through which oxygen was bubbled. He obtained a “ filtrate, neutral to litmus.” No other details of its composition are given. Up to this time it is clear that little success had been forthcoming in attempts to keep the isolated mammalian kidney alive, much less to function in a capacity approaching normal.