John A. Awad

A new approach to the management of familial hypercholesterolaemia: Removal of plasma-cholesterol based on the principle of affinity chromatography.

Reduction of plasma-cholesterol by the removal of low-density lipoproteins (L.D.L.) in an extracorporeal system is described as a possible approach in the treatment of familial hypercholesterolaemia. L.D.L. were removed from the blood by their interaction with heparin linked to agarose beads in the presence of calcium ions. Plasma-L.D.L. was markedly decreased in two patients with heterozygous familial hypercholesterolaemia. The technique is specific for the removal of L.D.L., as the concentration of high-density lipoproteins was not affected. The treatment was well tolerated by all three subjects (i.e., two hypercholesterolaemic patients and a normal volunteer), and there were no undesirable effects. Several haematological parameters, clinical-chemistry tests, including serum enzymes, and immunoelectrophoresis of plasma proteins were all unaffected by the treatment.

Expanded PTFE Prostheses as Arterial Substitutes in Humans: Late Pathological Findings in 73 Excised Grafts

Through collaboration of surgeons, pathologists and bioengineers at five centers in Canada and France, this study analyzed the late pathology and structural changes in 73 expanded PTFE arterial prostheses harvested from patients at autopsies and reoperations. The degree of tissue encapsulation increased with the duration of implantation but was reduced by the presence of infection. In several cases, the fibrous tissue penetrated the wall of the prosthesis and partitioned off the thin outer layer, thus disrupting the delicate microporous structure of the wall. The presence of aneurysms was observed in models that had no external reinforcing layer and among grafts that apparently suffered from surgical trauma. Wrinkling of grafts was noted at areas of flexion and was often associated with thickening of the external capsule and reduced luminal diameters. Endothelialization was found within only a few millimeters of the anastomoses. The luminal surfaces were generally not well healed. The PTFE structure was usually readily visible under a thin covering of loosely adhering thrombotic deposits. Bacteria were observed in 46% of the cases, even though only 29% were considered clinically infected. The incidence of lipid or cholesterol deposits was high. Avoiding iatrogenic trauma to the external wall of the prosthesis during implantation is important. Those features where design improvements are required to provide longer term structural integrity and dimensional stability in future models of expanded PTFE prostheses should be identified.

The benefits of fluoropassivation of polyester arterial prostheses as observed in a canine model.

The effect of treating the surface of a polyester vascular prosthesis with a novel fluoropolymer before sealing the graft with gelatin has been evaluated in a canine thoracoabdominal bypass model. The healing behavior of the Fluoropassiv graft was compared with that of the Gelsoft ERS prosthesis used as control for prescheduled periods of implantation ranging from 4 hr to 6 months. Both series of explanted grafts were analyzed using macroscopic, histologic, and scanning electron microscopic observations, and by determining the prostacyclin/thromboxane A2 ratio (PGI2/TXA2) and the thrombogenicity of the luminal surface by means of labelled platelets and fibrin deposition. Chemical analysis of explanted and cleaned graft segments was performed using electron spectroscopy for chemical analysis, differential scanning calorimetry, and contact angle methods. No difference in platelet and fibrin deposition or PGI2/TXA2 secretion by the luminal surface was observed between the treated and the control grafts at any implantation period. On the other hand, pathologic investigation has revealed that, although there is no difference between the two grafts during the first month, the healing sequence of the Fluoropassiv graft appeared more complete and mature than the control graft after 3 and 6 months. Differences were observed in the extent of collagenous internal capsular development, endothelialization, and tissue penetration into the knitted structure. The presence of fluorine and a higher contact angle at the surface of all the explanted fluoropassivated grafts is believed to have been responsible for reducing the inflammatory response and enhancing the long-term healing behavior of this novel prototype device over the control gelatin sealed prosthesis.

A compound arterial prosthesis: the importance of the sterilization procedure on the healing and stability of albuminated polyester grafts

In response to the demand for a vascular prosthesis which achieves reliable haemostasis without preclotting, a new compound albumin/polyester prosthesis has been developed. In order to optimize the sterilization procedures for this device, two series of implantations in the thoracic aorta of dogs were undertaken to compare the effects of ethylene oxide (EtO) and gamma-radiation. Preclotted polyester prostheses were implanted in two additional control series. Pathological analysis of the explanted grafts indicated that gamma-radiation is to be preferred over EtO because it results in faster rates of healing. While the albumin coating delayed the thrombotic response and fibrinolytic activity, the extent of healing of the radiation sterilized graft was equivalent to that achieved by preclotted polyester prostheses in the medium and long term. Measurements of the strength and dimensional changes of the graft demonstrated that, in addition to reducing the risks of acute thrombosis and postoperative haemorrhage, the albumin coating improves the dimensional stability of the knitted structure.

Pumpless Respiratory Assistance Using a Membrane Oxygenator as an Artificial Placenta: A Preliminary Study in Newborn and Preterm Lambs

Newborns suffering from severe respiratory difficulties and not responding to conventional methods have been successfully treated by extracorporeal circulation with a membrane oxygenator (ECMO). However, the technique needs a highly specialized staff, excellent laboratory support, and continuous surveillance of the procedure to prevent complications. In a series of experiments on newborn and preterm lambs, we have investigated a relatively simpler technique of respiratory support that involves a pumpless arteriovenous bypass by cannulating both umbilical arteries and the umbilical vein. A highly efficient microporous membrane oxygenator (MO) with very low resistance was selected. This type of perfusion that mimics the placental circulation, besides providing an additional amount of oxygen to the blood, has proven to be very effective for CO2 extraction. Before its application in humans, however, improvements in the catheters to be inserted in the umbilical vessels, some modifications in the design of the MO, and improvements in the blood compatibility of all foreign surfaces in contact with blood are needed.

Prolonged pumpless arteriovenous perfusion for carbon dioxide extraction

A method of extracorporeal carbon dioxide extraction from the blood using an efficient microporous membrane oxygenator or membrane gas exchanger was evaluated during pumpless arteriovenous perfusions with a view to its application for partial respiratory support. The first study carried out in dogs revealed some increase in cardiac output, cardiac index, and cardiac work, although this increase was less than that normally expected from the added extracorporeal blood flow. In sheep during 3 to 7 days of continuous bypass, there was practically no hemolysis and relatively stable hemoglobin and hematocrit levels, and the platelet counts remained within safe levels. The maximum extracorporeal blood flow tended to decrease from a mean of 1.55 L/min on day 1 to 1.34 L/min on day 3 to 1.28 L/min on day 7. Carbon dioxide extraction remained efficient throughout the perfusion, but there was a minimal decrease from the first day (10.92 mmol/L) to the third day (8.46 mmol/L) at the higher blood carbon dioxide concentrations; it remained stable thereafter at 9.0 mmol/L.

Blood Compatibility of Silicone Rubber Chemically Coated with Cross-Linked Albumin

A new method is reported for chemically coating cross-linked albumin onto silicone rubber in an attempt to improve the blood compatibility of the material. Promising results were obtained in an evaluation using both vena cava and renal embolus antithrombogenicity tests ondogs. Coated silicone rubber rings induced much less renal emboli than uncoated ones after one week implantation.

Dacron as Arterial Prosthetic Material: Nature, Properties, Brands, Fate and Perspectives

Dacron graft prostheses are routinely implanted to overcome impairment of arterial flow to distal tissues. Many different fabric configurations have been developped and evaluated. Unfortunately, after implantation the flow surface of any graft persists as a fibrinous lining. No human specimen has a commonly ingrown extension of tissue exceeding some millimeters in length. Full wall healing and endothelialization of arterial prosthesis is a goal that must be pursued intensively because it seems that the goal is attainable.

Extracorporeal removal of plasma lipoproteins by affinity binding to heparin-agarose.

Abstract The cholesterol circulates in the blood as a component of the plasma lipoproteins and its increased concentration in the low density lipoproteins is associated with a higher risk of atherosclerosis. We describe here the in vivo removal of cholesterol contained in low and very low density lipoproteins in dogs, based on the properties of these lipoproteins to form insoluble complexes with sulfated polysaccharides in the presence of divalent cations. Extracorporeal treatment of blood with heparin substituted agarose gel resulted in a progressive decrease in the circulating levels of cholesterol. Electrophoresis of lipoproteins, carried out on the plasma samples obtained before and after treatment in vivo showed that the decrease was mainly in the β- and pre-β-lipoprotein fractions. The α-lipoproteins were unaffected by this treatment. Similarily, the isolated high density lipoproteins from human plasma did not bind to the gel in vitro. Under the same experimental conditions, the low density lipoproteins showed a higher affinity for binding to heparin-agarose than the very low density lipoproteins. Also, when the whole blood or plasma was treated in vitro with heparin-agarose the percentage of cholesterol coupled by the gel was higher than the triglycerides. The heparin-agarose beads did not alter the concentration of various serum metabolites, enzymes, hormones and ions, however, a slight decrease was noticed in the total plasma proteins. Several hematologie measurements were also unaffected, indicating that the heparinagarose beads are compatible with human blood. Thus, removal of lipoproteins from blood by their affinity binding to heparin-agarose is an effective method for reducing the plasma cholesterol and experimentally, this procedure can serve to probe into the physiological mechanisms involved in the regulation and kinetics of cholesterol metabolism.

Endothelial Lesions Associated with Vascular Clamping - Surface Micropathology by Scanning Electron Microscopy

The endothelial cell pavement in normal blood vessels is very fragile. In cardiovascular surgery, the need for secure clamping of the aorta results in trauma which may be followed by thrombosis or occlusion. Various types of vascular clamps and other related devices offered commercially were clinically investigated in canine models and their effects on the vascular endothelium were ascertained with the aid of scanning electron microscopy. On the basis of these studies, the Fogarty silicone filled clamp appeared to be the least traumatic. However, further technical developments in this area are needed in order to obtain a completely atraumatic method of temporarily closing major blood vessels.