Extracorporeal Blood Oxygenation Research Articles

Extracorporeal Blood Oxygenation and Ozonation (EBOO) in Man. Preliminary Report

Autohemotherapy with ozone has been used for four decades with encouraging results but, owing to the lack of clinical studies, it has never been adopted by orthodox medicine. Confident of the valid principles of ozone therapy, we have endeavoured to increase its therapeutic efficacy. Over a ten-year period we have developed an apparatus that makes it possible to treat large quantities of blood with ozone in extracorporeal circulation (extracorporeal blood oxygenation and ozonation EBOO). One of us volunteered to test the system and after six treatments noted the disappearance of two lipomas. This prompted us to treat a patient with Madelung disease and several patients with atherosclerotic vasculopathy. Besides showing therapeutic effects, the preliminary results indicate that EBOO is clinically valid, without side-effects and worthy of testing in various diseases.

An enzymatic membrane reactor for extracorporeal blood oxygenation

The potential use of the enzyme catalase to oxygenate blood was investigated. A microcalorimetric technique was used to study the kinetics of oxygen generation in human blood serum at 25 and 37°C. Experiments carried out in serum and in phosphate buffer provided the apparent rate constants for the enzymatic and non-enzymatic oxygen-generation reactions. A simplified mathematical model was then developed to analyse the behavior of a hollow-fiber membrane oxygenator with catalase covalently bound to the membrane surface. The model was used to simulate an extracorporeal oxygenation treatment and outline differences with current devices.

Afterword: bottom-line status report: CAN current trends in membrane gas transfer technology lead to an implantable intrathoracic artificial lung?

For at least 170 years, attempts have been made to alleviate inadequate gas exchange of patients with respiratory failure. Major milestones in the struggle to assist failing natural lungs to achieve adequate blood gas exchange include utilization of oxygen inhalation therapy, mechanical ventilatory assistance, and development of both extracorporeal and intracorporeal mechanical blood gas exchangers. Current state-of-the-art technology related to mechanical membrane blood gas exchangers has produced highly efficient gas transfer membranes and designs capable of replacing all the gas transfer functions of the natural lungs by a mechanical oxygenator-CO2 remover that can fit into a unilateral thoracic cavity. The possibility thus exists of moving extracorporeal mechanical blood oxygenators into the body as an implantable intracorporeal artificial lung. Problems impeding the development of an implantable, intrathoracic artificial lung have been identified, and at least partially successful attempts to solve them have been reported. The conclusion drawn is that the appropriate answer to the question posed in the title of this communication is affirmative. Reasons for this conclusion include the persistent widespread major need for better relief from respiratory failure, the advanced state-of-the-art of mechanical blood gas exchanger technology, and the incompletely tapped ingenuity of the human mind.

Complement activation during cardiopulmonary bypass: Effects of immobilized heparin

The role of complement in biocompatibility reactions and the correlation between complement activation during cardiopulmonary bypass (CPB) and postperfusion syndrome have inspired attempts to improve the biocompatibility of extracorporeal blood oxygenation devices. Here we assessed the effect of immobilized heparin on the generation of C3a and terminal complement complexes during CPB. Thirty patients undergoing aortocoronary bypass were randomized to CPB with either heparin-coated (Duraflo II; Bentley, Irvine, CA) or noncoated control membrane oxygenators (Univox; Bentley). A standard dose of heparin (300 IU/kg) was given to the control group while the heparin dose was reduced to 30% (100 IU/kg) in the heparin-coated group. Significantly lower levels of terminal complement complexes were detected in the heparin-coated group by the end of CPB. From 28 ± 5 AU/mL (heparin-coated group) and 26 ± 3 AU/mL (control group, mean ± standard error of the mean) the terminal complement complex levels increased to 391 ± 35 AU/mL and 602 ± 47 AU/mL, respectively ( p < 0.002). This difference was still apparent 180 minutes after CPB. Although there was no difference in C3a levels between the two groups at the end of CPB, C3a levels were significantly lower in the heparin-coated group 30 minutes after CPB (194 ± 18 ng/mL and 307 ± 18 ng/mL in heparin-coated and control groups, respectively; p < 0.001). We conclude that the heparin-coated surface is more biocompatible with regard to complement activation than is the ordinary unmodifed surface in extracorporeal circuits.

A simple model for prediction of oxygen transport rates by flowing blood in large capillaries

A simple model has been developed for simulation of oxygen transport to and from blood flowing in conduits of the diameter of arterioles and larger (⩾ 20 μm). The basis is the large capillary model (LCAP) of P. K. Nair, et al. 1989 which has been validated experimentally. Detailed calculations of the oxygen concentration distribution reveal that the dominant resistance to oxygen transport is distributed in the plasma. Relatively little resistance is present within or in the immediate vicinity of the red cells. On the basis of these findings, LCAP was simplified from four simultaneous nonlinear partial differential equations (PDEs) to one PDE by (1) assuming chemical equilibrium within the red blood cells, (2) neglecting intracellular and extracellular boundary layer resistances, and (3) incorporating transport in the cell-free region adjacent to the capillary wall into the boundary conditions. The simplified model is much easier to apply mathematically to new situations. A comparison between LCAP and the simpler model shows that they give virtually the same predictions, and the predictions agree well with experimental measurements. The model is predictive in that all the parameters are determined from the literature or from in-independent measurements. Thus it should be useful in studies of physiological significance, as well as in design and analysis of extracorporeal blood oxygenators.

The physiological effects of fluorocarbon liquids in blood oxygenation.

AbstractThe objective of this study was to determine the feasibility of using a fluorocarbon liquid in a liquid‐liquid contacting device for extracorporeal blood oxygenation. Extraction experiments were carried out wherein blood was gently contacted with FC‐43 (a fluorinated tributyl amine) for up to 48 hr. The fluorocarbon caused no significant change in red cell volume, white cell count, plasma hemoglobin, platelet count, plasma fibrinogen, or the relative amounts of thirteen different plasma proteins. To determine toxicity, FC‐43 slugs and emulsions were injected intravenously and intraaortically into dogs. No chemical toxicity has been found, but the fluorocarbon is intolerable above about 1.7 mg/kg because it retards the flow of blood through pulmonary capillaries. FC‐43 was used for several in vivo tests of a vertical cylindrical blood oxygenator. The hemolysis caused by the falling film of fluorocarbon on the inner Teflon wall of the cylinder was considerably less than that caused by direct contact between blood and Teflon, suggesting that the blood‐fluorocarbon interface is quite atraumatic. All these results indicate that this fluorocarbon liquid holds considerable promise for use in a liquid–liquid blood oxygenator.

The Production of Microemboli by Various Blood Oxygenators

substantial body of evidence has shown that extracorporeal blood oxygenators alter blood in some way that eventually A damages the perfused tissue [8, 111. Some authors have suggested that microemboli are responsible, but detecting the presence of microemboli has been difficult [l, 4-7, 121. Recently a detection chamber employing ultrasound has been developed which continuously counts particles in flowing blood which are greater than 50 p [9]. Using this apparatus, a study was made of the relative concentration of microemboli produced by a disc oxygenator, a membrane oxygenator, and two types of disposable bubble oxygenators. The findings are reported here.

Extracorporeal oxygenation in puppies and in newborn and fetal lambs

1. Extracorporeal blood oxygenation was achieved by the membrane oxygenator described by Peirce and Galletti in 6 puppies, 1 to 4 months old, 7 near and at term fetal lambs, and 4 4-hour- to 4-day-old newborn lambs. The mean weight of the animals was 3,310 grams. Mean duration of extracorporeal assistance was 3 hours and 18 minutes. Mean extracorporeal blood flow rate was 104 ml. per minute per kilogram. Partial heart-lung bypass was achieved by right atrial venous drainage and carotid arterial infusion.2. None of the fetal animals breathed during the perfusion period; breathing in the newborn animals ceased at the beginning of the perfusion. The puppies were asphyxiated for different periods during extracorporeal circulation.3. Fourteen animals (out of 17) gained less than 4 per cent of their initial body weight.4. Satisfactory artificial oxygenation could be achieved but CO2 release was poor with the 0.5 mil thick cast Teflon membranes used. No problems of metabolic acidosis or electrolytic imbalance were encountered.5. Over-all survival rate was low (517) but higher (36) in puppies than in fetal or newborn lambs (211). The role of species, age, patency of shunts, anesthesia of the ewe, fetal anoxia before perfusion, coagulation defects, and endotoxic shock is discussed.

Laboratory experience with 24 hour partial heart-lung bypass

Summary Eight out of eleven dogs were long term survivors when submitted to 24 hours of partial heart-lung bypass using a membrane oxygenator with a low priming volume. It was possible to maintain an adequate metabolic balance in these animals and tests of hepatic and renal function after perfusion gave normal results. Blood damage during perfusion remained well within limits of compensation by the organism. However, the survival time of erythrocytes tagged at the end of the procedure was shortened, explaining the occurrence of hemolytic anemia in the first week after perfusion. Nonsurvivors showed pulmonary damage, water and electrolyte retention, splanchnic congestion and impairment of liver function. These experiments suggest that extracorporeal blood oxygenation can be offered safely for clinically useful periods with simple equipment requiring little or no priming blood.

Preliminary studies on the sponge-oxygenator; an improved simple method for extracorporeal blood oxygenation.

I N the development of an apparatus for extracorporeal circulation, the blood oxygenating device is the most difficult problem to be solved. Until now many ways have been followed to attain the aim of constructing a safe and efficient oxygenator, and some encouraging and praiseworthy results have been reached in bloodless open heart operations in man. Nevertheless the problem is still open and research for an even more perfect method is being continued. We began our experimental studies on this subject about 10 years ago, and during this time we have constructed and systematically tested on dogs many oxygenators based on the various principles pointed out by other authors and on our ideas.l-14 Recently 2 of us (A. B. and P. L. P.) have devised and realized a new system, the sponge-oxygenator, which proved to be the most safe and efficient we have experimented with to this time, In this report we shall not deal with the blood propelling parts of our apparatus, because the problem of the pumps may be regarded as a separate one. We shall expose only the structural features of the “artificial lung” and the first results experimentally obtained with it. The true oxygenation device is very simple. It is composed of a methyl methacrylate (Lucite; Plexiglas) 13 cm. long tube, with a 4 cm. internal diameter, containing a cylindrical piece of polynrethan spongei with large porosity. This cylinder is 10 cm. long and juts out from one end of the tube leaving a little unoccupied space at the other extremity (Fig. 1). The described device is fixed by simple pressure in the center of a bored support through which the venous blood and the oxygen enter the oxygenating tube by separate ways; the venous blood enters through 2 lateral channels and the oxygen through a long multiperforated needle fixed in a small renewable silicon rubber disc (Fig. 2). All around the central oxygenating tube, a deep circular groove acts as a collecting space for the arterialized blood ; the bottom is inclined toward the outlet hole (Fig. 3). The support

A simple circulatory bypass system.

SummaryThe use of an homologous lung is at present the simplest and most efficient method of providing extracorporeal oxygenation of blood. A simplified method of using such a lung experimentally has been described. In this experimental study of 12 animals there were 7 survivors, the 5 fatalities being caused by severe bleeding resulting from contaminated equipment.