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Cardiopulmonary bypass in the clinical setting is barely 40 years old. Yet worldwide, it is used in the operating room in more than 500,000 cases a year. This broad acceptance is a tribute to the vision of gifted investigators who could see beyond the mere technical problems of perfused isolated organs. They integrated mechanical concepts, knowledge of materials, and sheer inventiveness with an appreciation of physiological issues to address the clinical needs of open-heart surgery.

This article points to the importance of penetrating micropores through the graft wall to minimize thrombosis and to enhance endothelialization in small diameter polymer skin coated vascular grafts. Four types of spongy polyurethane-polydimethylsiloxane vascular grafts (PUG) fabricated by a spray, phase-inversion technique, 1.5 mm inner diameter, 1.5-1.9 cm in length, were implanted end-to-end in the infrarenal aorta of 26 adult rats. Some had a continuous inner skin and a hydraulic permeability (HP) of 0 ml/min/cm2/ 120 mmHg (PUG-S-O). Some had an inner skin with varying amounts of isolated penetrating micropores and a mean hydraulic permeability of 11 (PUG-S-11), 37 (PUG-S-37), or 58 ml/min/cm2/120 mmHg (PUG-S-58). Twelve PUG-S-O, 6 PUG-S-11, 4 PUG-S-11, and 4 PUG-S-58 were evaluated between 2 hr and 3 months after implantation. All PUG-S-O occluded soon after implantation. The PUG that had a HP of more than 11 ml/min/cm2 showed acceptable patency. However, endothelialization was limited to anastomoses in patent PUG-S-11. In contrast, the patent PUG-S-37 and PUG-S-58 were largely endothelialized. In all patent grafts at 3 months, numerous host cells had migrated, and newly formed capillaries were seen in the voids of the graft wall, which appeared moderately to highly cellular. In conclusion, it appears that penetrating micropores through the graft wall increase patency and that a highly porous structure is needed to achieve extensive endothelialization in small diameter polymer skin coated vascular grafts.

Two types of spongy polyurethane-polydimethylsiloxane blend (Cardiothane 51, Kontron Instruments, Inc., Everett, Mass.) vascular grafts with an internal diameter of 1.5 mm were fabricated by a spray, phase-inversion technique. Low-porosity grafts with hydraulic permeability of 2.7 ± 0.4 ml/min per square centimeter and medium-porosity grafts with hydraulic permeability of 39 ± 8 ml/min per square centimeter displayed good handling properties and suturability. Twelve straight low-porosity grafts, 17 straight medium-porosity grafts (1.5 to 2.0 cm in length), and one loop medium-porosity graft (10 cm in length) were implanted by the same surgeon end to end in the infrarenal aorta of 30 male Sprague-Dawley rats. Three months after implantation, patency was 8% for low-porosity grafts (1/12) and 76% for straight medium-porosity grafts (13/17). The loop medium-porosity graft was also patent. The sole patent low-porosity graft showed neointimal hyperplasia and incomplete endothelialization. All but one of the patent straight medium-porosity grafts showed a glistening and transparent neointima with complete endothelialization and no anastomotic hyperplasia. The loop medium-porosity graft displayed endothelialization from each anastomosis and in many islands in the middle portion of the graft, totaling 47% of the luminal surface by morphometric analysis. Thick mural thrombus, anastomotic hyperplasia, or aneurysm formation were not observed in any patent medium-porosity graft. These data indicate that in the rat aortic replacement model it is possible to achieve patency and a high degree of endothelialization in very small-diameter prostheses of appropriate porosity.

A highly porous, distensible, gel-like tubular membrane suitable for a small diameter arterial prosthesis was fabricated by combining techniques for spraying and phase-inversion of thermodynamically unstable solutions of a biocompatible polyurethane (PU)-polydimethylsiloxane (PDMS) blend (CardiothaneTH51) over a sliding and rotating mandrel. The cylindrical membrane was characterizedin vitro for mechanical, morphological and permeability properties, and evaluatedin vivo as a 1.5 mm internal diameter prosthesis for the replacement of the rat abdominal aorta. A mature, stable luminal interface, a thin internal capsule without anastomotic hyperplasia, and the deposition of collagen within the voids of the polymer mesh were observed after 8 weeks of implantation.

The growth and differentiation of an established renal epithelial cell line, LLC-PK1, on membrane bound mussel adhesive protein (MAP), collagen, and extracellular matrix (ECM) in serum-containing medium was studied. Cell attachment and growth on uncoated- vs. protein-coated cellulose nitrate and acetate membranes did not differ significantly, and confluence was achieved on all membranes. However, cells remained in a single monolayer only when plated on collagen or ECM. LLC-PK1 monolayers grown on ECM-coated membranes displayed the highest transepithelial D-glucose transport (333 +/- 22 ng.cm-2.min-1) whereas cells plated on collagen-coated membranes displayed the lowest (94 +/- 23 ng.cm-2.min-1). Glucose flux values increased with age of the culture, reaching a plateau at 28 d postseeding. These results indicate that the underlying substratum and cell age can affect differentiation of renal epithelial cells in vitro.

The influence of microporous structures in the walls of small-diameter arterial prostheses was investigated with the aim of minimizing thrombosis and enhancing endothelialization of blood-contacting surfaces. Six types of spongy polyurethane-polydimethylsiloxane grafts (PUG), 1.5-mm in an internal diameter and 1.5–2 cm in length, were implanted end-to-end in the infrarenal aorta of 66 adult rats. Some had a continuous inner skin and a hydraulic permeability (HP) of Oml/min/cm2at the standard transmural pressure of 120mmHg (PUG-S-0). Some had a discontinuous inner skin with some isolated windows connecting penetrating micropores though the graft wall and a mean HP ranging from 11 (PUG-S-11) to 37 (PUG-S-37) or 58 (PUG-S-58) ml/ min/cm2. The rest had a microporous inner surface with penetrating micropores through the graft wall and a mean HP of 2.7 (PUG-2.7) or 39 (PUG-39) ml/min/cm2. PUG which had a HP of less than 2.7 ml/min/cm2showed poor patency. PUG with a HP of more than 11 ml/min/cm2had acceptable patency, but endothelialization was limited to their anastomoses. In contrast, the patent PUG-S-37 and PUG-S-58 were largely endothelialized and all but one of the patent PUG-39 implants were completely endothelialized. In conclusion, penetrating micropores through the graft wall appear to inhibit critical mural thrombosis. A microporous inner surface seems to be superior to a skinned inner surface in achieving a high degree of endothelialization.

Worldwide, 30–50 million men and women benefit from implanted devices. Therefore, the clinical experiences with synthetic materials in intimate contact with human cells and tissues exceeds by three orders of magnitude the number of laboratory animals sacrificed in the elusive quest for “biocompatibility.” Furthermore, the much longer duration of observation characteristic of human implants, compared to animal studies, adds two orders of magnitude to the superiority of clinical and anatomopathological experience over laboratory animal studies. This glaring disparity must be kept in mind in the assessment of materials through in vitro and small animal studies, and the regulatory agencies’ pronouncements based on such evidence. Another sobering fact is that over 95% of the materials utilized for implants are standard commercial substances originally developed for industrial purposes. Those products which have been found to be appropriate for a specific medical device are labeled “biomaterials” (or more modestly, materials for medical use) on the grounds of established specifications and quality control, supported by continuing feedback from the clinical experience. The major obstacle to the advent of custom-designed biomaterials is that the medical device market is so small (not in numbers of implants and impact on health care budgets, but in the quantity of material used per implant) that large-scale production and amortization of industrial production expenditures is well nigh impossible for truly novel substances. In litigious countries such as the USA, suppliers are pulling out of the market because of the excessive cost of defending against legal action when materials allegedly fail in the body environment. Against this background, biomaterials science is bravely searching for new solutions to old problems. The ill-defined property of biocompatibility is slowly making way for the notion of bio acceptance as we expand our knowledge of the cellular aspects of tissue-material interactions. Bioacceptance can seek two diametrically opposed end points: biointegration, meaning that the material and the surrounding living structures form a continuum with stable, low-grade interactions; and biopassivation, meaning that the material is hardly recognized by surrounding body fluids or tissues and that its stealth characteristics can persist for clinically meaningful periods of use.

This study addresses a long-lasting controversy, ‘Which is a better blood-contacing surface morphology, smooth or rough?’ and indicates the importance of micropores penetrating through the graft wall in minimizing thrombosis. Four types of spongy polyurethanepolydimethylsiloxane (Cardiothane 51; Kontron Instruments, Everett, MA, USA) vascular grafts (PUG), 1.5 mm ID and 1.5–2cm in length, fabricated by a spray, phase-inversion technique, were implanted end-to-end in the infrarenal aorta of 58 adult rats. Some grafts had a continuous inner skin and, consequently, a hydraulic permeability of 0 ml/min per cm2 (PUG-S-0). Some had an inner skin with isolated pores and a mean hydraulic permeability of 11 ml/min per cm2 (PUG-S-11). Some had a microporous luminal surface with a mean hydraulic permeability of either 2.7 ml/min per cm2 (PUG-2.7) or 39 ml/min per cm2 (PUG-39). Twelve PUG-S-0, 6 PUG-S-11, 23 PUG-2.7, and 17 PUG-39 were evaluated between 2 hours and 3 months post-implantation. Almost all PUS-S-0 occluded with thrombus soon after implantation. PUG-2.7 had poor patency. Both PUG-S-11 and PUG-39 showed acceptable patency. Endothelialization, however, was limited to 1–2 mm from proximal and distal anastomoses in any patent PUG-S-11. In contrast, all but one of the patent PUG-39 were completely endothelialized. The extent of mural thrombosis decreased in the order from PUG-39 to PUG-S-11, PUG-2.7, and PUG-S-0. In conclusion, micropores penetrating through the graft wall, as reflected by hydraulic permeability values, appear to inhibit critical mural thrombosis and to promote a high degree of endothelialization.

The expression "medical device" covers any diagnostic or therapeutic means which involves a specific object and exerts its effects by mechanisms other than pharmacological. As such the term "device" includes a broad variety of instrumentation ranging from artificial organs to dental and orthopedic prostheses, biomaterials, biosensors, implants of various kinds, tissue engineering products, tools for minimally invasive procedures, imaging and patient monitoring equipment, telemedicine, hospital support systems (organizational and managerial) used for screening, diagnostic or therapeutic purposes, and systems for human rehabilitation.

The American public's perception of biomedical engineering is fuzzy, and consequently, the expectations for services provided by the profession vary widely. This becomes apparent whether one talks to scientists in academia; manufacturers of medical products who employ biomedical engineers; doctors who either see technology through the narrow view of their specialization or as generalists are one step removed from technological innovation; patients who under the stress of disease cannot distinguish between standard and experimental forms of treatment; and finally government agencies which in the main have failed to define a place for biomedical engineering in their programs, and therefore oscillate between the extreme perspectives of biomedical engineering as a basic medical science and that of a service profession. As President of AIMBE, the American Institute for Medical and Biological Engineering, an umbrella organization which groups the majority of bioengineering societies (Table 1), I have witnessed and rationalized this confused perception as the uneasy coexistence of two realities: a scientifically mature field of inquiry impacting in both medicine and engineering, and a globally perplexed, almost balkanized profession, scattered among so many subgroups that no global identity can be defined and presented to the public.

Cardiopulmonary bypass (CPB) is used so routinely in hospitals around the world that most of the participants — surgeons, anesthesiologists, perfusionists, operating room nurses and, above all, patients — forget that this landmark in clinical technology is not even 40 years old. In fact, many of the pioneers are still active in the field. Yet, so much has been done to transform a once-hazardous procedure into standard medical practice — through basic science, quality control, and good manufacturing — that one hardly remembers the days (not so long ago) when “pump-oxygenators,” as they were graphically called, were assembled just outside the operating room by tinkerers with a dream. The purpose of this chapter is to recall the inventiveness displayed by a small coterie of gifted investigators to whom we owe the mechanical and physiologic foundations of open-heart surgery, and to reflect on the new demands that continuing clinical advances will undoubtedly make on this technology.

The woven tubes membrane oxygenator is a suitable configuration for the intracorporeal membrane oxygenator because of a high gas exchange performance and a compact packing of tubing. In this study the oxygen transfer performance of woven tubes was evaluated by an in vitro experiment with an external perfusion mode; the blood flow is outside of the tubes in order to reveal the feasibility of designing the intravascular oxygenator (IVOX) by the woven tubes. The oxygen transfer efficiency of the external perfusion mode is superior to that with the internal perfusion mode because of the larger convective mixing effect on the external surface of the tubes. Thus the use of the external perfusion mode results in the shorter necessary tube length for the rated condition, which enables making the oxygenator unit more compact. All of these features encourage the adoption of the woven tubes for use in the intravascular oxygenator.

EPLACING R a defective component of the body or substituting for a deteriorated organ function by a natural or man-made counterpart is one of the major contributions of modern science to clinical medicine. My objective in this essay is to draw some lessons from the experience with organ replacement in the last 40 years, and to project where substitutive and reparative medicine may lead us in the decades ahead. If the generalized practice of organ replacement is a recent phenomenon, the idea of substituting in some manner for body parts lost by accident or worn out by disease is apparently as old as mankind. Witness for man-made implants the use of gold plates to cover traumatic skull defects in several ancient civilizations. Witness for external support systems the technology for grinding rock crystal into the vision-correcting lenses allegedly used by the emperor Nero, and quite widespread in the western world since the 13th century. Witness, in the case of transplantation, the geographic transfer of knowledge regarding pediculated skin flaps to reconstruct the nose from ancient origins in India seven centuries before Christ, to Alexandria in the Ptolemaic period, and then through Arabic conquest of the Mediterranean coast, to a lineage of barber-surgeons in Southern Italy in the late Middle Ages, and finally to Tagliacozzi who, in the 16th century, codified in Bologna an operation that is still practiced today. What is new to our times is not so much the impact of modern science and technology on organ replacement procedures. as the epic scale on which substitutive and reparative medicine are now, rather suddenly, being practiced.

Microporous prostheses of 1.5 mm internal diameter were fabricated with a polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE)n co-polymer by the spray phase inversion technique. Some of the grafts were made piezoelectric by poling under a high electrical field. Overall, 24 poled grafts (P) and 24 unpoled grafts (UP) (15-22 mm in length) were implanted in the infrarenal aorta of 48 adult rats. Patency rates in P were 100% (8/8) at 2 days, 100% (8/8) at 2 weeks, 75% (6/8) at 6 months, and 92% total (22 of 24). Patency rates in UP were 100% (8/8) at 2 days, 63% (5/8) at 2 weeks, 100% (8/8) at 6 months, and 88% total (21 of 24). Thus there was no significant difference in patency between the two types of grafts. Both showed similar macroscopic and microscopic findings. At 2 days, fibrin deposition was somewhat heavier on the poled grafts, but no difference in surface platelet deposition could be detected. Endothelialization was observed from both anastomoses at 2 weeks and was almost complete at 6 months. The excellent biocompatibility of PVDF-TrFE and the microporous structure of the grafts were probably the dominant factors in success with these grafts. Although piezoelectric activity in excised cleaned poled prostheses remained significantly higher than that in the control UP, the charges developed may have been too small to exert a biologic effect, either because of insufficient dipole orientation or inadequate mechanical deformation.

Bioartificial organs combine the physical aspects of implantable prostheses with the biological advantages of organ transplantation. Enclosing live cells in a permselective, synthetic envelope avoids rejection by an immunoincompatible host while the geometric limitation of the closed polymer capsule prevents overgrowth of the transplanted material. As a tenet bioartificial organs widen the range of therapeutics based on the biological activity of cell transplants and open an alternative path to gene therapy.

A serpentine gas exchange unit was built with cylindrical tubular microporous membranes featuring periodic arcs with a fixed curvature ratio (ratio of tube radius to radius of curvature) of 1/14 and circular angles between 30 and 360 deg. Oxygen transfer was measured under steady and pulsatile blood flow conditions in vitro and ex vivo to assess the design features which most effectively augment gas transfer. Under steady blood flow conditions, oxygen transfer increased with circular angles beyond 70 deg. Under pulsatile conditions, a wide range of geometrical and fluid mechanical parameters could be combined to enhance gas transfer performance, which eventually depended upon the secondary Reynolds number and the Womersley parameter.

Mechanical systems to oxygenate blood outside of the body were first employed in clinical medicine as a component of the «heart-lung machine». The artificial lung has been an essential component of the technology underlying the progress of cardiovascular surgery since 1950. Its impact on clinical medicine can be measured by the widespread acceptance of cardiac surgery for the treatment first of congenital malformations, then valvular lesions, and more recently, coronary artery disease. Whereas the use of the artificial lung during temporary exclusion of the pulmonary circulation for surgical purposes is now well established, the chronic application of extracorporeal membrane oxygenation in end-stage respiratory failure is still controversial. Internally implantable lung prostheses are still at the conceptual or developmental stage, and are unlikely to impact on clinical medicine for another decade.

The brain tissue reaction to permselective polymer capsules implanted in rats was evaluated for 1 to 54 weeks. The polymer capsules were well tolerated in all animals and no recognizable neurological or behavioral deficits were associated with the implants. Necrosis at the brain/polymer interface, as assessed with Nissl stain, was not observed. Foreign body giant cells were consistently absent. Immunocytochemically identified reactive neuroglial cells showed a remarkably low-grade tissue response to the synthetic material be yond the first 2 weeks of observation. Immunolabeled cortical neurons revealed conserved columnar arrays around the implants. Transmission electron microscopy showed a minimal degree of collagen deposition compared to implants in peripheral sites, and normal synapses within a few micrometers from the brain/polymer interface, supporting the prospect of biocompatible, immunoisolated xenografts in the central nervous system.

Annuli have been built with longitudinal grooves or splines on both inner and outer tube surfaces, using microporous teflon tubing with appropriate extruded cross-sections. Axial twisting of the tubes (which makes the splines helical) gave enhanced mass transfer, counter-twisting being more effective than co-twisting.

The peritoneal cavity is a convenient site for implantation of encapsulated hormone-secreting tissue. However, host tissue organization around such implants may affect solute exchange and viability of the encapsulated tissue. The reaction to polyvinyl chloride acrylic copolymer capsules implanted in the peritoneal cavity of rats and mice was therefore studied. Some animals received a slow release dexamethasone pellet, others were pretreated with doxorubicin, in an attempt to minimize the tissue reaction. The tissue reaction was significantly thicker in rats than in mice at both 2 and 6 weeks after implantation. In rats, corticoids decreased significantly the thickness of the reactive layer as compared to control at all time points studied, but doxorubicin had no effect. The tissue reaction in mice was not significantly affected by corticoid treatment. In both species the thickness of the tissue reaction did not increase significantly between 2 and 6 weeks. At 3 days the tissue reaction consisted of an interrupted single layer of macrophages in mice, whereas in rats the reaction consisted of two or three layers of macrophages and polymorphonuclear cells. At both 2 and 6 weeks, several cell layers surrounded the implants: a single layer of macrophages lying along the polymer, a variable number of layers of fibroblasts interspersed with collagen fibrils (fewer in mice than in rats, and fewer in corticoid treated rats than control rats) and an outer monolayer of mesothelial cells. We conclude that the intensity of tissue reaction to polymer implants in the peritoneal cavity is species dependent and can be decreased by the administration of corticoids but not doxorubicin.

Since hypothermia is commonly used to lower local and general metabolism during cardiopulmonary bypass, we attempted to identify its specific effects on glucose-insulin interactions. A group of nondiabetic patients undergoing hypothermic (28 degrees C) cardiopulmonary bypass with ischemic (cold) cardiac arrest was compared to a similar group operated on under normothermic conditions with potassium cardioplegia. In the absence of exogenous dextrose administration, hypothermia blocked insulin secretion for the duration of the operation. It also inhibited insulin secretion in response to an exogenous dextrose load (e.g., the priming fluid of the cardiopulmonary bypass circuit) or a glucagon injection, but this inhibition was lifted by rewarming. Blood glucose levels, which during normothermia were mildly elevated even in the absence of dextrose administration, remained normal during the hypothermic phase of cardiopulmonary bypass. By the end of the rewarming period, however, blood glucose levels had reached the same level as observed under normothermic bypass, a fact suggesting that the cold inhibition of hepatic glucose production had been only temporary. Cold inhibition of hepatic glucose production also explains why glucose clearance after a sudden dextrose load was initially faster at low body temperature than at normal temperature. Glucose-clamp studies indicated that insulin resistance was initiated by anesthesia and surgical trauma, and further accentuated by cardiopulmonary bypass, in association with elevated levels of hormones indicative of surgical stress. Regardless of body temperature changes, the assimilation of glucose by nondiabetic subjects during and immediately after bypass called for the infusion of large doses of insulin. A comparison with diabetic subjects showed that insulin-dependent patients (type I diabetes) required no more insulin during cardiopulmonary bypass than normal subjects, whereas patients with type II diabetes exhibited a marked insulin resistance during the operation and in the immediate postoperative period.

A technique allowing the deposition of an adherent thin film of turbostratic, high-density carbon on heat sensitive polymers was recently developed. The biological response to this biomaterial on yarns and fabrics of the type used in cardiovascular surgery has been studied. Polyester yarns, knitted Dacron® sheets and knitted uncrimped Dacron® vascular grafts were coated with a thin film (less than 1 μm) of turbostratic carbon using a physical vapour deposition process. Coated and control discs of knitted material, as well as coated and uncoated yarns, were implanted in pairs in the subcutaneous tissue of mice, using for each type of implant two cohorts of 12 animals, with observation periods of 4 and 8 wks respectively. Vascular grafts (8 cm long, 8 mm i.d.) coated with carbon on the luminal side only, were implanted for 12 wks in the infrarenal aortic position in six dogs, and compared to uncoated Dacron® grafts of the same dimensions inserted in the same location and for the same duration in the infrarenal aortic position in six control animals. With subcutaneous implants, there was no significant difference in the tissue reaction to either coated or uncoated patches. In contrast, the vascular grafts, all of which were patent upon retrieval, showed a much lower extent of thrombosis on the blood-exposure surface in the case of carbon-coated Dacron®, as compared to the luminal surface of control prostheses. The internal capsule (tissue formed between the polymer fabric and the blood interface) was thinner in carbon-coated grafts than in control grafts. No giant cells were observed on the Dacron® fibrils coated with turbostratic carbon, which in all cases remained firmly adherent to the polymeric substrate.

Leakage of lactate dehydrogenase and staining by the vital dye trypan blue were investigated in adult rat hepatocytes at the time of isolation, in suspensions up to 3 h and in primary monolayer cultures up to 3 d. These two parameters of plasma membrane integrity were found to correlate closely in hepatocyte suspensions, but to a lesser degree in monolayer cultures. Functional activity was demonstrated in culture by glucose consumption and lactic acid production. There was a balance of total lactate dehydrogenase (LDH) activity over time for both hepatocyte suspensions and cultures. Loss of LDH activity in the cell fraction was accompanied by a corresponding increase in enzyme activity in the media fraction. Lactate dehydrogenase activity per dye-excluding hepatocyte was calculated to be 9.2 +/- 1.5 X 10(-6) IU assayed at 37 degrees C for 25 preparations of isolated hepatocytes. The results suggest that leakage of cytoplasmic enzyme and vital dye staining are of comparable sensitivity in evaluating hepatocyte preparations. Measurement of LDH leakage offers a less subjective alternative to cell counting procedures and is applicable to both attached and suspended cells.

Decreases in cardiac efficiency have been observed in experimental endotoxic shock, acute hemorrhage, and cardiopulmonary bypass. Diminished coronary blood flow, tissue anoxia, or metabolic alteration may affect the contractile protein which, in turn, causes cardiac inefficiency. To test this hypothesis, cardiac actomyosin and myosin were extracted with Guba-Straub solution, and intrinsic viscosity, ATP (adenosinetriphosphate) activity, ATP sensitivity, the rate of ATP hydrolysis, and myosin-ATPase activity were determined. Under these experimental conditions, both myosin and actin were altered. In order to exclude the possible effect of hypoxia of the arterial blood upon the cardiac contractile system, acute hypoxia was produced in dogs and the physicochemical properties of actomyosin and myosin were studied. During acute hypoxia, the myosin-ATPase was affected, but actin appeared to remain unaltered. These changes of actomyosin and myosin may cause insufficient energy utilization by the contractile system and thereby affect the cardiac efficiency.

Evidence is presented that reflex systemic vasodilatation occurs after stretching dog's lungs by either mechanical traction or positive pressure ventilation under conditions of separate pulmonary and systemic perfusion. This reflex is mediated by the vagus.

Fluid and electrolyte balance was studied in 21 dogs after partial heart-lung bypass of 10 hr duration. Water retention was demonstrated by an increase in body weight and total body water, primarily due to an increase in extracellular fluid. Electrolyte retention was suggested by an increase in total extracellular sodium, potassium, and chloride. Urinary output was relatively normal but a progressive drop in urinary specific gravity was observed during bypass. Blood pH remained essentially unchanged. However, an increase in plasma lactate and a decrease in plasma bicarbonate suggested some degree of hypoxia and metabolic acidosis at the cellular level. Altered hormonal regulation of sodium and water excretion, hemolysis secondary to blood trauma, and the exchange of intracellular potassium for extracellular hydrogen ions were considered possible explanation for the fluid and electrolyte changes observed. assisted circulation; heart-lung bypass; acid-base balance; fluid balance; extracorporeal circulation; electrolyte changes with partial bypass; membrane oxygenator; disc oxygenator; bubble oxygenator Submitted on June 20, 1963

Prolonged administration of a daily dose of 5-10 mg. of fluoride to patients with hyperthyroidism may cause clinical improvement together with a significant fall in the level of plasma protein-bound iodine and a reduction in the basal metabolic rate. Studies with radioactive fluorine failed to demonstrate any important accumulation of fluorine within the thyroid in vivo. Thyroidal, blood and urinary radioiodine studies suggest that fluorine inhibits the thyroid iodide-concentrating mechanism. Fluorine does not impair the capacity of the gland to synthesize thyroid hormone when there is an abundance of iodide in the blood. However, inhibition of the thyroidal concentrating capacity when the total iodide pool is low will impose a critical limitation of hormonal synthesis, and may explain the therapeutic effect.