The purpose of this paper is to clarify regional hemodinamics and gas metabolism during extracorporeal circulation under normothermia in extreme hemodilution.
Six mongrel dogs were placed on extracorporeal circulation with a rotating disc oxygenator under normothermia. The venous return was separately collected from the SVC (S), coronary vein (C), abdominal caval vein (M), femoral veins (F) including both the renal veins and intracardiac bronchial return (B). The pressure and flow measurements, and the arterial and venous blood sampling for gas analysis were made at the various deglee of hemodilution with the hematocrit (Ht) value of 35, 30, 25, 20, 15 and 10%.
The total perfusion rate was about 84ml/min/kg throughout the study. The blood flows in S and C areas increased significantly in the state of extreme hemodilution with a Ht value of 20%. The blood flow in M area decreased significantly when the Ht value became less than 20%. The total oxygen consumption and carbon dioxide excretion were significantly decreased below the Ht value of 20%. The respiratory quotient was increased to more than 1.24 in all areas at the 10% of Ht value.

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In order to evaluate the factors involved in microembolism with and without donor blood during extracorporeal circulation (ECC), blood filters were studied under the scanning electron microscopy (SEM). The results obtained are as follows: 1). The SEM pictures were classified into four types according to the degree of occlusion of the filters and the degree of deposits of aggregates, fibrin and blood components. 2). The SEM pictures in ECC with donor blood all belonged to Type I. 3). The SEM pictures in ECC without donor blood belonged to Type II, III, IV. More than half of them belonged to Type IV. 4). The embolic materials were reduced remarkably in ECC without donor blood.

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Extracorporeal circulation was performed in dogs with a perfusate containing 0.6 to 2.5Gm/dl of hemoglobin and 11 to 20Gm/dl of Perfluorochemical emulsion (PFC). The oxygen consumption increased as the oxygen delivery was enhanced by increasing the perfusion rate. The consumption however, did not increase over a certain value even though the delivery was raised over 8ml/Kg B. W./min. The maximal oxygen consumption was a_little less than 5ml/Kg B. W./min at 37°C, and this amount of oxygen consumpton was obtained when the oxygen delivery increased over 8ml/Kg B. W./min. The minimal perfusion rate necessary to meet the maximal oxygen consumption in dogs was about 120ml/Kg B. W./min when the arterial oxygen content was kept in the range of 6 to 7 volume % by the use of PFC, even though the hemoglobin content was reduced to less than 1.2Gm/dl.

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As an alternate approach for relief of the severe obstruction of the left ventricular outflow tract, the bypass procedures from the left ventricular apex to the descending thoracic aorta, “APICO-AORTIC BYPASS”, using the valve composite conduits, were performed in the experimental animals without use of cardio-pulmonary bypass. The satisfactory henodynamics results during the early postoperative periods were observed. The clinical applicability of the procedures was also discussed.

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Poor perfusion of the aortic arch proximal to the tip of the cannuia was demonstrated during cardiopulmonary bypass with ascending aortic cannulation.
Theoretical analysis based on a model of ascending aortic perfusion revealed that the jet from the cannula decreased the retrograde flow and the effect of the jet was severest in case of a small aortic arch.
In children a thin walled perfusion catheter should be used.

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Study on hemodynamics was performed during cardiopulmonary bypass (CPB) in 87 patients. Arterial, superior and inferior vana caval pressures were measured by pressure transducers. Superior and inferior vena caval return were measured by an electromagnetic flowmeter, They were continuously measured and recorded on a multichannel recorder. Signals of rotation rate of rollerpump and urine dripping were also recorded in some of cases. Oscillating flow in the drainage tubings were observed in 40% of cases. It was originated from oscillatory vibration of the vena caval wall due to excessive negative drainage pressure. The oscillating flow in the drainage tubings suggested postperfusion hemolysis and influence on the renal function. The peripheral vascular resistance of inferior vena caval area was revealed to be decreased when the aorta was clamped during stabilized condition of CPB. Vascular compliance was decreased and resistance was increased following the time of CPB.

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Renal perfusion experiments were performed in thirteen dogs to evaluate the effects of perfusion pressure during normothermic preservation.
Histological examination showed no difference between pulsatile and nonpulsatile perfusion, however, the results of renal function tests showed that pulsatile perfused kidney had better functions than nonpulsatile one, and mean pressure should be maintained higher than 80mmHg to keep better renal functions.
Based on these results, the new pulsatile roller pump was developed for futher investigation. This pump, driven by the stepping motor, is able to control by the electrical control unit. Many types of flow pattern are generated and mean perfusion pressure is able to keep constant by this system.

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The effects of pulsatile and mnpulsatile flow on renal energy metabolism was studied. For the unilateral depulsation without compromising the integrity of either renal artery, the abdominal aorta was interrupted between the ostia of the renal arteries and depulsated blood flow was led to the left renal artery through the femoral artery.
After rapid freezing of renal tissue, the assay of adenine nucleotides was made enzymatically. Rapid decrease of energy charge level was shown on the depulsated renal tissue, especially when the mean arterial pressure was low at 60-70 mmHg.

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We studied the efficacy of valveless pulsatile assist divice(PAD), which was developed by Bregman et al, The PAD not only converts roller pump flow; into pulsatile flow, but also can be used as an arterial counterpulsator before and after cardiopulmonary bypass.During cardiopulmonary bypass, pulse pressure of 40-50mmHg was obtained in all cases.
Compared to cardiopulmonary bypass alone or combination of cardiopulmonary bypass and IABP, additional effect of PAD on renal perfusion was recognized experimentally, and urinary output during cardiopulmonary bypass in man was appreciablly greater.

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Closed circuit of extracorporeal circulation was used in the experimental study of pulsatile and non-pulsatile perfusion in dogs.
Depulsalator bag and infusion control line, used in the venous line, were practical to maintain CVP and perfusion flow reasonably for a long term. After the setting of perfusion flow, the stability of perfusing state of the system was maintained simply by the control of the roller pump in the infusion control line.
In comparison with pulsatile and non-pulsatile perfusion, a slight difference of tissue Po and Pco were observed in the changing time of perfusion mode, using mass spectrometer, catheter in muscles and cortex of kidney. And also the difference of mean aortic pressure, slight increase of pressure in non-pulsatile perfusion, was observed.

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Total heart-lung bypass wit h closed circuit was performed under automatically controlled CVP, and oxygen consumption and fraction rate of SVC and IVC return were studied in our previous report.
In this report histological changes of the liver, portal vein pressure, cerebral drainage and total systemic peripheral resistance during heartlung bypass were discussed in variously controlled CVP. Consequently, during our closed circuit heart-lung bypass, 7-9 cmH₂O CVP was recommended to minimize histological and metabolic changes and to keep venous return stable.

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When we analyse fluid mechanical properties of heart valve prosteses, the primary requirment of the valves is low flow resistance. Recent artificial valves usually show sufficient low resistance. But the dynamic characteristics of these valves are not enough to prevent thrombus formation at the valves, valve cracks or valve disfunction. The reasons are these valves have stagnation points of blood flow line around the valves, produce strong water hammer pressure waves at valve closure, and frequently make thrombus at valve pivots. The future heart valve prosteses should be developed with thin high polimer membrane, and their characteristics are low flow restistance with perfect center flow stream and minor stagnation points. These valves should be formed less stress structure at valve closure and the orifice of the valves may be non-circular irregular shape as natural mitral valves. Incidentally, the development of these valves depends upon the development of the material of biomedical polimers.

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Since the successful clinical application of cardiac prostheses, 17 years has been elapsed. In these era, there were various kinds of cardiac prostheses such as fabric leaflet type as the first, then caged ball valves or caged disc valves, at the same time eccentric monocusp types and bioprostheses treated in different manners have been utilized in a fairly goon numbers.
Some of them have been modified in design to improve clinical results. According to our 16 years' clinical experience, we have evaluated the principal features required to clinically implantable cardiac prostheses especially from the standpoint of structural design.
Although it seems to be ideal that cardiac prostheses which provide a central flow in hemodynamics, on the other hand, the material which contacts to blood stream should be non-thrombogenic at the same time should be strong enough not to be wear in more than 20 years after implantation. However, valves currently available are not satisfied in the mitral area because of it's relatively much more higher frequency of postoperative complications rather than in the aortic ones.
Therefore, it is still very difficult to determine the ideal type of the cardiac prosthesis for replacement of the cardiac valves.

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Glutaraldehyde preserved porcine aortic xenografts have been widely used clinically in the recent years.
Improvement of the hemodynamics after implantation of the grafts and reduction of the thromboembolic episords without anticoagulation have been described in the literatures.
The further observations of their pliability and durability, however, will be necessary on the basis of clinical, pathological and echocardiographic findings.

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Prospects of prosthetic valves can be viewed in the following three stages, long future, future, near future.
In the long future, the development of preventive medicine will decrease the rheumatic valvular diseases and the use of prosthetic valves may be limited to smaller series of diseases, for example, mitral regurgitation due to papillary muscle damage caused by myocardial infarction and aortic regurgitation caused by dissecting aneurysm of aorta.
In the future, the development of the science of high molecule will provide us with ideal prosthetic valves which can be used for more than 20 years without any complication and the valves will be applied even to moderate valvular disease of N. Y. H. A. class II or III. The operative risk and prognosis will be much improved.
In the future, partial repair of valvular disease (enlargement of leaflet, chordoplasty, annular plication and so on) will be performed with improved suture materials and prosthesis (leaflet with chorda and so on ) of good quality high molecule.
In the near future, suture technic will be improved and prosthetic valve replacement with adhesive component will become possible.

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With the experience of homograft valve replacement of more than 10 years, the author's prospect for bioprosthetic valves from the view point of surgical technique is presented. In comparison with rather reliable long term durability of chemically treated homograft aortic valves inplanted in mitral or aortic position, the duration of commercially available xenograft valve is not considered to be always superior to that of homograft. Some ideas to improve the sewing cuff for the bioprosthetic valve, which seems to have the possibility to be realized in near future, are described.

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This paper reports the biochemical studies about healing process of synthetic vascular grafts in the canine subcutaneous tissue from 3 to 12 weeks post implantation, that is, about mucopolysaccharides changes of the connective tissue surrounding the graft and proceeding lumen-ward through the interstices. Uronic acid and hexosamine in the connective tissue 3 weeks after implantation were more than B and 5 umole/g. dry wt. respectively, and maintained approximately the same values during the whole period. In electrophoretic analysis, the major components were hyaluronic acid and dermatan sulfate with lesser amounts of chondroitin sulfate and negligible amounts of heparan sulfate. Hyaluronic acid accounted for 32-40% of the total mucopolysaccharides, and the value of which means sustaining of heavy tissue reaction.
Our data suggests that the complete healing of these grafts should require still longer period than generally estimated.

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Direct hemoperfusion with albumin coated, bead shaped, micro-encapsulated, activated charcoal and hollow fiber kidney were performed so times on is patients of hapatic coma.
survival of 3 patiens and improvement of consciousness in 7 patients were observed. In autopsy, the liver histology of almost cases without any clinical effect for direct hemoperfusion showed massive necrosis.
after 3 hours direct hemoper fus ion, elevated plasma amino acid level were lowered and some kinds of plasma amino acid, especially Threonine and Methionine were remarkably decreased.
However, remarkable change in chemical data of liver function was not observed.

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THe ND-12 is a small., lightweight parallel-flow dialyzer. Within the case, a single sheet of Cuprophan of 11.5μ in thickness is folded in size of 5.5cm in width and 30cm in length to fiom 45 blood channels. 3 spacers and polypropylene mesh contained in each dialvzata channel serve as membrane supnort. Effective surfacearea is approximately 1.24m², urea and creatinine clearances are 140ml/min, 110ml/min, respectively at a blood flow of 200ml/min and dialysate flow of 500ml/min. ultrafiltration rate 3ml/mmHg/hr, priming volume is 100ml and the pressure drop across the dialyzer for blood is SOmmHg whereas the dialyzate pressure drop is 30mmHg. In Vivo clearances for urea and creatinine are 140±4ml/min, 110±3ml/min respectively, ultrafiltration rate is 2.2ml/mmHg/hr, the blood and the same as that of Vitro data. The removal rate of urea creatinine and uric acid are 72.2±5.2% 63.3±4.1% and 70.4±4.0% respectively at a blood flow of 200ml/min and dialysate flow of 500ml/min in 6-6.5 hrs dialysis. In using this dialyzer for chronic in dialysis patients, no one showed deterioration in clinical conditions, hepatic functiors and blood system.

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In recent years, the appearance of disequilibrium syndrome which may be caused by acetate as an acid-base balance buffer in dialysate solutions becomes a problem. In atempt to resolve this problem, composition of dialysate has begun to be reviewed for improving clinical conditions of patients by substituting physiological bicarbonate for acetate.
However, as bicarbonate dialysate will lose carbonate within dialysate wwth the change of pH, the problem remains that composition of dialysate cannot be fixed and accordingly bicarbonate dialysate cannot be used with current dialyzing system.
We, therefore, systematize dialysate supply unit and monitoring unit for bicarbonate dialysate to improve above mentioned problem by (1) preparing 2 dialysate solutions one contains bicabonate, another dose not.
(2) adopting two ways of continuous mixing system of dialysate supply unit.
(3) adopting indirect dialysate heating system.

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