Life support systems : the journal of the European Society for Artificial Organs最新文献

Biocompatibility is redefined as the quality of being mutually tolerant with life. In so far as this represents a quality which is as likely to be achieved as is the alchemist's dream of turning lead into gold, a compromise approach is recommended. It is suggested that all extracorporeal or body invasive procedures stimulate the inflammatory defence mechanism of the body by stimulating the monocyte to produce a family of polypeptides currently known collectively as Interleukin-1 (IL-1). So far two dissimilar gene products have been cloned and there are probably more. The IL-1 group of polypeptides possess hormonal functions which orchestrate nearly every instrument of the body's defence system. Inducers of IL-1 are present in dialysate and induce bacterial pyrogen and acetate. In addition bacterial cell wall glycoprotein may be cleaved into muramyl peptides by the release of granulocyte lysozyme at the membrane interface. Muramyl dipeptides have been found in CAPD drain fluid and are more potent inducers of IL-1 than endotoxin. Membrane activation of the fifth component of the complement with the release of C5a will also induce monocytes to produce IL-1. The consequences of repeated stimulation of the acute phase response are undesirable and may include muscle wasting, osteopenia and bone cysts (Shrinking man syndrome), fibrosis of scapulo-humeral joints and the carpal-tunnel syndrome. These latter lesions are often associated with deposition of amyloid fibrils related to beta 2-microglobulin. Efforts to reduce these complications are urgently required.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthetic polymers used in extracorporeal circulatory devices promote or exacerbate inflammatory responses. We have developed a sensitive reproducible centrifugation assay to measure adherence of 111indium-oxine labelled leukocytes to synthetic membranes; the effects of various conditions such as duration of incubation, the presence of chemotactic factor or presence of protein on the extent and strength of attachment of human leukocytes to artificial membranes were studied. Adherence of leukocytes to the membranes was found to be time dependent, especially during the initial stage of incubation. The presence of plasma in the medium, or a plasma protein-precoated surface, markedly inhibited adhesion of leukocytes. The number of leukocytes adhering to protein-treated surfaces was ten times lower than for untreated surfaces. All tested membranes, Polypropylene 2402, Supor 200 Hiflow, Cuprophan 100 PM and The True Membrane reacted in similar way with the exception being the Tuffryn HT-650 membrane. Titration with leukocytes indicated that cells incubated in PBS adhered as a monolayer, whereas cells incubated in plasma did not. The percentage of leukocytes adhering to the polypropylene membranes was reduced in a concentration-dependent fashion by chemotactic peptide fMLP.

The concept of 'reconstructive cardiac surgery' using a stimulated autologous skeletal muscle has been investigated in this research. Our approach has been to investigate the substitution or reinforcement of a ventricular wall by a contractile tissue. The experiments have demonstrated the feasibility of this technique and the long-term adaptability and adequate electrophysiological properties of the Latissimus Dorsi flap transferred to a heterotopic position over the heart. Long-term biocompatible fatigue resistant muscle stimulation has become possible in experimental and clinical cases as a result of the development of specially designed electrodes and the use of a progressive sequential stimulation protocol to adapt the skeletal muscle to a cardiac support function. Autologous pericardium treated with glutaraldehyde was found to be a suitable material to close the ventricular cavity. Cardiomyoplasty with autologous skeletal muscle to restore ventricular contractility seems to be a valid alternative in addition to current methods of treatment for irreversible myocardial failure.

We analysed the impact of the area of the dialysis membrane and of its content in hydroxyl moieties on the magnitude of haemodialysis-induced complement activation and leucopenia. First, in five patients successively treated with cellulose acetate membranes of different areas, we found that increase of the area results in an increase in complement activation determined by C3a levels before and at 15 min of dialysis. The levels of leucopenia were similarly affected, and a significant correlation was found between complement activation and leucopenia (r = 0.89, P less than 0.05). When we compared the biocompatibility characteristics of a dialyser made of saponified cellulose ester with those of two dialysers made of cellulose acetate, we found that index of complement activation (18.1 +/- 2 vs 9.9 +/- 1.1 and 11.5 +/- 1.1, P less than 0.01) as well as index of leucopenia (69 +/- 4 vs 40 +/- 2 and 37 +/- 3, P less than 0.001) were significantly higher on the saponified cellulose ester dialysers suggesting that hydroxyl groups of cellulosic membranes play an important role in the pathophysiology of dialysis-induced changes.

Biocompatibility evaluations are a complex issue involving not only classical toxicity and animal testing but also the interactions of biological systems. The evaluations of the Therapore Primary System are reported for three model systems: (1) in vitro human blood, (2) a baboon (Papio anubis) animal model, and (3) normal human volunteer apheresis. Measurements of both complement (C3a) and platelet (BTG and TXB2) activation products during the apheresis procedures are given as a sensitive indicator of biocompatibility. No statistically significant elevations of these activation products were observed. Thus, the Therapore System was found to have negligible perturbations of the interacting biological systems evaluated even with the highly sensitive RIA procedures employed. These observations and methods establish a solid foundation for comprehensive biocompatibility evaluations of future extracorporeal devices.

Since the total amount of haemoglobin in blood is constant during haemodialysis, haemoglobin concentration reflects changes of blood volume caused by ultrafiltration and solute transport. Haemoglobin concentration therefore could serve as a control parameter for ultrafiltration. Blood is taken continuously from the arterial blood line at the very small rate of 0.1 ml/h and diluted at a constant ratio of 1/200 by a sterile solution 0.05 per cent NH3. By the diluting medium the erythrocytes are haemolysed and the haemoglobin is transformed into oxyhaemoglobin. The haemoglobin concentration is determined measuring the absorbance at 415 nm. The error in the measurement of the haemoglobin concentration is less than 3 per cent. The method was tested in vivo during 10 haemodialysis treatments of five patients. Haemoglobin concentration appeared to reflect the well-known effects of ultrafiltration, of food intake and changes of position (sitting, lying). If the body weight approached the suspected dry weight, haemoglobin concentration increased more rapidly. During high ultrafiltration rates (1.0 litre/h) and sudden changes of ultrafiltration rate haemoglobin concentration seemed to be unevenly distributed in the vascular space. If haemoglobin concentration indeed reflects changes in blood volume the method can be used to study the relationship between blood volume and blood pressure in haemodialysis therapy and to control ultrafiltration.