We have developed a new-Na infusion pump with six infusion pattern systems. This machine is useful in Na gradient dialysis in dialyzate central supply system. The beginning concentration of Na in dialyzate is the alternative of 150mEq/l or 144mEq/l, and the terminal concentration is the field of 134mEq/l to 138mEq/l in all cases. We can perform the non-symptomatic dialysis against the patients with dialysis disequilibrium syndrome, and can treat the machine easily. We think Na gradient dialysis using our systems is the excellent method for adequent dialysis in dialyzate central supply system.
The HSCD has been expected to increase the solute clearance with only a minimal disturbance in the circulatory function. Its clinical application, however, was restricted because of the abnormal sodium balance induced by the its continuous use. We made a concentration-controllable sodium infuser, DKJ-11 (NIKKISO), and have used it as a delivery system of additional dialyzate sodium in the HSCD. This paper is to evaluate the HSCD with the new infuser. The measured dialyzate sodium concentrations closely correlated with their theoretically expected values (r=0.991, p<0.001). In spite of the removal of about 4 liters of body fluid by this method, it was shown that hypotensive episodes were reduced to 15% and the range of serum sodium concentration at the end of dialysis was 139-142mEq/L, resulting in less magnitude of thirst. These results indicate a beneficial effect of the HSCD with this infuser by means of serial change in the dialyzate sodium concentration.
A programmed infusion system for high sodium dialysate has deen devised and clinically evaluated. Sodium concentrasion of dialysate can be changed in a step-wise from 135mEq/L to 157.7mEq/L and duration of each step can be choosen every 30minutes. Clinically favorable effects of the programmed high sodium dialysate were shown with this system.
New methods modified dialysate for dialysis treatment, such as high Na, sodium gradient, and cell-wash, have been used. In order to provide the all above ciethods avilabe, we have developed a dialysate supply device for a single patient, which offers the possibility of the necessary water removal volume to allow estimate volume to set up before dialysis, as well as the possibility of changing water removal volume every 30 minutes. We have assessed the device in following three methods, 1) High Na dialysis method 2) Sodium gradient dialysis method 3) Cell-wash dialysis method and reported here about 1) Mechanism 2) Function 3) Clinical effect
Until now, it has been possible to remove metabolite and Na from the blood by the method of dialysis using low Na dialysate, however, the removal rate of metabolite from cells and the correction of cell edema has not yet been sufficience accomplished. There fore, in order to facilitate metabolism within the cell by actively removing substances which collect in the cell as well as by controlling cell edema, we have conceived of a Cell-Wash dialysis method using alternetery low and high ha dialysate. From the end of last year, this method has been adapted for use which dialysis patients suffering from diabetic nephropathy with severe cell edema as well as with dialysis patients suffering from chronic glomerulonephritis while causes headache, loss of appetite, fatigue, acid articular pain. The symptomes have been sufficiently improved. At this time, I would like to report on the results of a study comparing the conventional dialysis method using low Na dialysate and the Cell-Wash method, on creatinine, and guanidines which especially accumulated in the cell, and other substances.
As an inevitable possibility of bicarbonate infuser to be connected with single pass dialysate delivery system, there in a possibility of precipitation of carbonate salt in the system. Our novel device “Bicarbonate Infuser” also have this potential possibility. In order to find an appropriate composition to prevent this precipitation, the present study was done. With this device, solution “A containing Na (113.2±0.1mEq/L), K (2.72±0.005mEq/L), is to be mixed with solution” B containing Na (134.6±0.47mEq/L), K (2.47±0.02mEq/L) and HCO3 (27.1±0.42mEq/L) on use. In this study, four kind of sodium bicarbonate including 8, 6, 5.3 and 4.5% in “B” solution was tested. The changes of pH was always uphill along the time course at every, concentrations. Total Ca remained stable only with 4.5% concentration. Ionized Ca showed random distribution among four kinds of concentration. Thus, optimum sodium bicarbonate concentration in this device in solution “B” is 4.5% in conclusion.
Sixteen patients were treated by conventional hemodialysis in bicarbonate dialysate with newly deviced technique. Dialysate pH during session was quite stable with no addition of acid and non CO2 bubbling tank system which contained 8.1% of NaHCO3. We checked the effects of degassing in delivery system and the influence of distance and diameter in delivery system with open and closed modes. Results were as follows; (1) Dialysate pH in 8.1% NaHCO3 solution with open system was higher than with closed system during session: (2) Dialysate bicarbonate, total Ca, ionized Ca and Mg concentration were not changed in both dialysate delivery system with open and closed modes. (3) Chnges in dialysate pH and Pco2 with dialysate delivery system of 8mm diameter line were much less than with that of 19mm diameter line.Same results were obtained in delivery line with different distance. (4) The effects of degassing in delivery system were marked dependent in Po2 and independent in Pco2. Dialysate pH, Pco2 and bicarbone were very stable in bicarbonate dialysate with degassing and non-degassing dialysate delivery system Correction of acidosis were very satisfactory in both system.
Urokinase (UK) was immobilized on seven different kinds of polymer surfaces using our newly devised technique. The carriers of UK ware (1) nylon-6, (2) nylon-11, (3) polyester elastomer (PE), (4) silicone rubber, (5) polyvinyl chloride (PVC), (6) polyurethane (PU) and (7) ethylene vinylacetate copolymer (EVA). The UK-itmobilized materials were clinically applied and the antithrombogenicity was evaluated. 89 of the UK-immobilized tubes, 1, 2, 3, 5 and 7, ware used as drains in thyroid, breast, abdominal and thoracic surgery and 17 of PVC-UK drains surved in cardiac surgery. 75 of UK-imnobilized tubes, 1, 2, 3 and 7, were also applied as intravascular (IV) catheters. The average duration of the clinical use of these tubes ware 4.5 days in surgical drains and 21.6 days in IV-catheters. The patency of the UK-immobilized drains applied in general surgery was 93.30, as for the IV-catheters, 92.0%, while that of the control (non-treated PVC) drains was only 4.60. The details were sirrrnarized in Table 1. The antithrcanbogenicity of PVC-UK drains which had been applied in cardiac surgery was also moderate: they were almost patent during the clinical use, while the control tubes were often obstructed with blood coagula and both milking of the tubes and thranbectomy were frequently carried out to keep the lumen patent. These results are shown in Table 2. In this study, it is concluded that EVA-UK tubes are good for IV-catheters and PVC-UK tubes are also adequate for surgical drains.
Coimmobilization of antithrombin III and heparin on artificial polymers such as silicone, polyvinyl alcohol and poly-HEMA has been found to inhibit the blood coagulation, and thereby to depress thrombogenic nature of these artificial biomaterials. However, antithrombogenic activity of coimmobilized antithrombin III and heparin (I-ATIII·Hep) was limited, since the inhibitory effect of I-ATIII·Hep was due to the complex formation with activated coagulation factors. In the present study, coimmobilization of urokinase with ATIII·Hep was introduced to add fibrinolytic activity to biomedical materials. CNBr-activated Sepharose 4B beads was used as carrier, on which a complex of antithrombin III and heparin, and/or urokinase were immobilized. Immobilized preparation of urokinase (I-UK) could effectively convert plasminoaen to plasmin. Although clotting time of blood samples from rabbit or canine was prolonged by I-UK, antithrombogenic activity of I-UK was less than that of I-ATIII·Hep, as compared on the basis of unit amount of dry weight of carrier. A mixture of I-ATIII·Hep and I-UK, or coimmobilized preparation of ATIII-heparin complex and urokinase, exhibit a pronounced antithrombogenic activity, even when individual activity (inhibition of coagulation, or fibrinolytic activity) was not so high. It was concluded that coimmobilization of ATIII-heparin complex and urokinase was a promising approach to endow a biomedical material with high antithrombogenic activity.
The lifetimes of immobilized UK on sulfonated poly vinylidene fluoride (PVDF) films and silicone·ollagen graft were measured. UK activity immobilized on PVDF films became undetectable at 70th day with 40 days half lifetime. On the other hand, UK activity immobilized on silicone·collagen graft tubes was still active at 210 days with 180 days half lifetime. The lifetime of 350 days was extrapolated from the decay curve. The patency of the graft tube implanted in the aorta of a dog was clearly observed at 360th day by the angiography. The amount of immobilized UK on silicone·collagen graft depended on the process of chemical treatment.
Currently, there is an increasing need to develop better medical materials with high antithrom—bogenecity. Attempts have, in fact, been made to improve such materials by the following methods; 1) to develop a material compatible with tissue, 2) to coat amaterial with protein, 3) to immobilize an anticoagulant agent on the surface of a material. and 4) to immobilize a fibrinolytic enzyme on the sur face. Among these methods, the last is intriguing. As already reported, immobilized Urokinase can maintain fibrinolytic ability. Reported herein are the outcomes of the fundamental and clinical studies on Urokinase treated EVA (ethylene-vinyl acetate eopolymer) tube which is used as intravenous catheter. The results are as follows: 1) This tube has 7.9±1.8U of urokinase activity per 10cm. 2) The activity was influenced by the procedure of EOG disinfection. 3) This activity decreased after the repeated fibrinolysis test. 4) This tube showed an antitbrombotic action in clinical trial and maintained the almost 10% of initial activity.
Polymers which have microphase separated structure on its surface show good antithrombogenecity. However, the role of microdomains on thrombogenesis, especially platelet adhesion and aggregation has not yet been investigated. We have synthesized block or graft copolymers composed of 2-hydroxyethyl methacrylate (HEMA) and styrene chains, and block copolymers composed of HEMA and dimethyl siloxane chains, which exibited microphase separated structures. Using these polymers, interaction between polymers and platelets were investigated with regard to influence of 1. shape, 2. size and 3. chemical structure of microdomains on platelet adhesion. As to these three factors, the most appropriate microphase separated surface was implied. These investigation suggested the possibility of controlling cell adhesion and deformation by means of domain regulation.
Vinyl chloride tube has been widely used as a material of circuit for the cardiopulmonary bypass and assisted circulation. However the antithrombogenesis of the vinyl chloride tube is not sufficient enough. The Avcothane ® coating on the surface of vinyl chloride tube was performed in order to imporve the antithrombogenesis of it. Pilot experiment showed the problem of Avcothane coating, that is lack of durability. Six kind of Avcothane ® coating techniques were applied to improve it's durability, and in vitro test was performed. This test showed that the durability of Avcothane ® coating can be slightly improved by using the glue, for example mixed solution of Avcothane ® and vinyl chloride.
In order to evaluate antithrombogenic materials, many methods have been invented. But none could show how many days the materials remain patent when used clinically as shunts. We made A-V shunts between femoral artery and vein with tubes made of antithrombogenic materials in rabbits to evaluate the antithrombogenicity. The tubes examined here are made of polyethylene, silicone rubber, teflon and a heparinized hydrophilic polymer. The outer and inner diameter of the shunts were respectively 2.0-2.5mm, and 1.4-1.5mm with the length 20cm. The average patent days were 2 days with polyethylene, 2.6 days with silicone rubber, 3.6 days with teflon and 10.2 days with the heparinized hydrophilic polymer. This method has proved to be more practical and valuable for clinical use.
Silicon devices have much potentials for artificial organs, sensory aide, indwelling and implantable medical sensors, and intra- or extra-cellular biological instrumentation. For these purpose one of the most important characteristics is blood compatibility. The blood coagulation test of elementary materials related to silicon integrated circuits, packages, and polymers was made by the Sahli-Fonio method. The 0.1ml of native blood was placed on the sample which was previously heated at 37°C for 15min. The average clotting time of nine tests was expressed in the percent of control value (Teflon). Among elementary materials Si3N4 is the longest(63%). As packages a plastic package is the longest (75%). Parylene C is the longest (77%) among polymers. Since the clotting time of Si is 33% the surface of Si should be coated by parylene C.
A series of ethylene-vinyl alcohol copolymers (EVOH) were tested with respect to the relationship between thrombogenesis and content of hydroxyl groups of polymer. Both the surfaceactivation of contact phase coagulation factors and the platelet adhesiveness on polymer surface were measured using rabbit and canine plasma and platelet-rich plasma. Six copolymers with different content of vinyl alcohol were tested and compared with popular biomedical polymers such as silicone and teflon. As judged by surface-activation of prekallikrein, EVOH 30 (30mole% of vinyl alcohol) was the best copolymer, followed by EVOH 0 (polyethylene) and EVOH 100 (Polyvinyl alcohol) which were comparable to silicone. Platelet adhesiveness test with citrated canine PRP, selected EVOH 100 as the most preperable copolymer. Platelet adhesion on the surface of EVOH 100 was as low as on to f lon surface. EVOH 0 was the second best, but the maximum adhesiveness and deformation of platelets were observed on EVOH 50 and EVOH 65. Polyvinyl alcohol was the best of the series of polymers tested. However, the effects of polymer surface on platelets and coagulation factors were not necessarily consistent.
Antithrombogenicity of silicon rubber mixed tungsten powder were evaluated by using the technique of autoradiography with I-fibrinogen. Catheter of silicon rubber mixed tungsten powder were insert into the inferior vena cava through the right jugular vein of rat. As soon as set the catheter, intravenous injection of I-fibrinogen is performed from rat's tail. In two hours to seventy days after the insertion of catheter, 40u of longitudinal frozen section of rat were made by whole body cryotome. Autoradiograms were produced by exposure the rat section to the X-ray film for two to four weeks. Thrombus formation surrounding the catheter which were detected by autoradiogram with I-fibrinogen using rat and were little seen compared with silicon rubber which have ever been used.
Changes of rabbit platelet aggregation stored in test tubes made of plasticized polyvinylchloride, silicone rubber and heparinized hydrophilic polymer (H-RSD) have been investigated. Rabbit blood was directly introduced into test tubes which contained one volume of 3.8 sodium citrate (anticoagulant) from jugular artery without contacting any other materials than the test material. Then the tube was tightly sealed by mechanical clamping and was centrifugated to prepare platelet rich plasma (PRP) in the tube and again mechanically clamped to separate PRP from the residual precipitant. In situ, the PRP was stored in the test tube at room temperature under agitation. The effects of preservation of the PRP on platelet aggregation response induced by ADP and collagene were studied and simultaneously the scanning electron microscopic studies on the platelet adhered onto the inner surface of test tubes above mentioned were performed. In plasticized polyvinylchloride tube, ADP induced aggregation was completely lost after one day storage and in silicone rubber tube ADP induced aggregation reduced to about 50% of initial value after one day storage. To the contrary, in H-RSD tube ADP induced aggregation was slightly enhanced after one day and remained even after two days preservation. Scanning electron microscopic studies demonstrate that the aggregation of platelets stored in test tubes reduces as the number and the degree of deformation of platelets adhered onto the inner surface of test tubes increase.
The formation of an insoluble fibrin network plays an important role in the process of wound healing. To form such an insoluble fibrin, thrombin, a blood clotting factor XIII (F XIII) and Ca++ are required. For the enhancement of local fibrin accumulation, we immobilized thrombin and F XIII on absorbable gelatin sponge and also on some suture materials using our newly devised technique. Basic studies on the degree of fibrin formation on the materials both in vitro and in vivo showed that a large amount of fibrin had formed, Even in tissue liquid containing less fibrinogen than plasma, remarkable fibrin network had formed. Moreover, the fibrin network formed in vivo adapted well with the tissues. On the other hand, no fibrin formed on the control materials. Clinically, the immobilized suture materials were used for skin suture and the extraction force to take out the sutures was measured by tension meter on the 8th postoperative day. The result suggest that much fibrin formed and the fibrin network adapted well with patients subcutaneous tissue. As a model of embolus formation in vessels, we used Chandlers roatating tube method, In this tube, large embolus formed on the immobilized sponge in a moment. So, we utilized the sponge as a thrombogenic material for transcatheter embolization. The embolization was successful and 2 monthes after, no recanalization could be seen. We are going to utilize these for promotion of wound healing, protection of anastomosis, transcatheter embolization and so on.
A simple in vitro method is required for a primary screening test of prominent blood compatible biomaterials. A new method investigated here was based on the surface-activation of plasma prekallikrein which was the triggering reaction of the contact phase blood coagulation. By this method, the rapid activation of prekallikrein was observed when plasma came in contact with kaolin or glass. On the other hand, artificial polymers such as ethylene-vinylalcohol cppolymer, polyvinyl alcohol, silicone, teflon and polyethylene were found to activate merely small amount of prekallikrein. The extent of surface activation of prekallikrein was varied when the surface of polymer was modified by immobilizing proteins and/or other compounds. Heparin immobilized on Sepharose 4B decreased the activation of prekallikrein as compared with nonmodified Sepharose 4B. When heparin was coimmobilized with antithrombin III on the same carrier, further decrease in surface-activation was observed, suggesting that the excellent antithrombogenic activity exhibited by the coimmobilized preparation was ascribed not only to the inhibition of activated factor X and thrombin but also to the repression of surface-activation of prekallikrein.
Cells were incubated on poly (methyl methacrylate), segmented polyurethane and segmented polyester films with three different types of surface roughness, and the effects of roughness on cell attachment and cell growth were compared. On rough surfaces, initial cell attachment was promoted, but rate of cell growth was inhibited as compared with smooth surface. Sensitivity of cell attachment and growth behavior to change in roughness depended on the polymers used. Importance of roughness in tumorigenicity and thrombogenicity of materials is discussed by comparing the results obtained here with those reported in literatures.
We previously described how we developed a new method of producing antibacterial biomaterials by the immobilization of hen egg-white lysozyme and polypeptide antibiotic Polymyxin B onto the surface of collagen-synthetic polymer composite materials. We implanted this lysozyme-bearing composite material into rabbit dorsal subcutaneous tissue, and investigated its histological reactions, especially the reaction of immobilized lysozyme in the tissue of a different species. In the early stage of the implantation, the lysozyme-bearing composite material caused a less inflammatory reaction and formed a thinner connective tissue layer than the composite material without immobilized lysozyme. After five months, there were no remarkable differences between the composite materials with immobilized lysozyme and without immobilized lysozyme in terms of the inflammatory reaction or in the thickness of the connective tissue layer.
Cells were incubated on various segmented polyurethanes with poly (tetramethylene glycol ether) soft segments in the range of 856-2000 molecular weight and with two types of chain extender, and cell attachment and cell growth were compared. In one series polyurethane, initial cell attachment seemed to increase and rate of cell growth to decrease with the increase in molecular weight of soft segments. However, in another series, polyurethane with the soft segment of 1350 molecular weight gave a minimum cell growth response. Effect of surface morphology on cell attachment and growth behavior is discussed.
In this paper the authors report the biochemical studies about healing process of synthetic vascular grafts, i. e. commercially available prosthesis (Dacron and Teflon) and Non-Woven Polypropylene Sheat compounded with Dacron Mesh in the canine subcutaneous space, and some grafts in the canine abdominal aorta. The content of mucopolysaccharides in the collagenous connective tissue surrounding the implants and extending into the cloth interstices was studied. The histological studies by means of hematoxyline and eosine stain revealed the almost complete healing of the subcutaneouly imbedded Double Velour KD graft, the tissue healing of which was the most favorable in this study, about one to two years after implantation. But, the biochemical studies revealed sustaining of the inflammatory response in all of the subcutaneous implants in the same period. The most severe tissue reaction continued in the surface of the lowest porous fabric (Woven Teflon graft), the data of which suggest there is a strong relationship between the ratio of the percent open area to the fiber diameter and the inflammatory response. The extremely remarkable inflammatory tissue reaction was observed in Non-Woven Sheat in the early period after the subcutaneous imbedding, but the inflammatory response decreased favorablely to the same level as found in the other fabrics except Woven Teflon about one year after implantation. It is suggested that this graft is associated with favorable healing attributes. The content and the components of mucopolysaccharide in the canine abdominal aortic grafts were quite different from those of the subcutaneous implants. The content of mucopolysaccharide and the ratio of chondroitin sulfate to dermatan sulfate were higher, and the negligible amount of hyaluronicacid was found in the former. The authors believe that these changes were brought about mainly by the arterial pressure. Therefore, the place of the implantation should be taken into consideration for the estimation of the tissue healing of the implanted materials.
The materials of vascular prosthesis was discussed in the respect of the healing process of the implantation. The author maintains that vascular prosthesis must have properties of an antithrombogenecity in the early stage of the implantation and an affinity to the connective tissue in the long term. In the experiments of implantation of vascular prosthesis made from antithrombogenic substances, good patency rate was obtained in the early stage and the surface of the prosthesis removed was covered with a thin layer of proteins, however, pannus formation was observed at the anastomotic lines in every cases of long term. The tendency of the endothelization against the foreign body (vascular prosthesis) was very firm, and the prosthesis have to keep preventing the endothelization for all time. While in the case of vascular prosthesis which have no antithranbogenecity, the prosthesis was tended to be obstructed by thrombus. However, once the endothelization was established, the prosthesis keep patent with the assistance of thromboresistance of endothelium. The materials of the prosthesis was encapsulated with connective tissue under the endothelium. From these results, the author propose the properties of vascular prosthesis mentioned above.
In order to study blood compatibility of stable fibrin, its contact angle at the solidwater interface, its anticoagulability and its ability of cell adherence were investigated. Porous vascular grafts were implanted in canine abdominal aorta after preclotting with fibrin. The results were as follows: 1) Surface of fibrin was highly hydrophilic. 2) Surface of fibrin produced with low content of thrombin had higher anticoagulant activity than with high content of thrombin. 3) Colonies of HeLa cell were formed onfibrin membrane in 24 hours. 4) Materials produced with low content of thrombin had more smooth and cleaner surface than with high content of thrombin after 3 hours implantation. On the materials that were recovered 4 weeks after implantation, there was good tissue incoporation or healing on the inside of the grafts.
Anastomotic false aneurysms occurred 8.2% in patients who were successfully implanted blood vessel prosthesis in our clinic since 1964. The occurrence in patients those were sutured with silk was 19.2% being higher than that of patients sutured with Dacron materials. The experimental study which was implanting grafts with absorbable or nonabsorbable suture materials showed that when the arterial wall was healthy and there were no healing complications the tensil strength of suture material was under 15% of whole anastomotic strength. But in the presence of any healing complications, the strength of suture material was higher than 30% of whole anastomotic strength. If there are any pathologic changes in patients'arterial wall the suture line will be easily brocken down when the tensil strength of suture material declines.
Neointimal fibrous hyperplasia (NFH) at the anastomosis of prosthetic vascular grafts is a major cause of the graft occlusion. Because a factor of NFH is early thrombus formation at the anastomosis, anticoagulat and fibrinolytic agents were studied of the effectiveness. Inner diameter 6mm Gore-Tex grafts were implanted in 26 mongrel dogs. These dogs were devided to four groups (control, heparin, urokinase, heparin+urokinase). Two weeks after implantation, the thrombus thickness at the anastomoses were measured. The mean values were 125 in control, 52μ in heparin, 48μ in urokinase, 20μ in heparin+urokinase. 3 months after implantation, when endothelial cells covered the inner surfaces, the mean values of the neointimal thickness were 460μ in control, 325μ in heparin+urokinase. Heparin and urokinase reduced the thrombus formation at the anastomoses, but did not prevent NFH so prominently. We thought that the proliferative procedure by myofibroblasts must be modified to prevent NFH.
The anti-thrombotic effect of ticlopidine was examined in dacron vascular prostheses with 4mm in caliber implanted in the femoral arteries of 10 beagle dogs. The treated dogs were those daily administered with ticlopidine 50mg/kg per os from one day before to 2 weeks (2 dogs) or 4 weeks (3 dogs) after the implantation. The graft patency in the treated dogs was 50% (100% patency with the exception of infected grafts) in 2 weeks-cases and 100% in 4 weeks-cases, while they were 0% and 33%, respectively, in the control dogs. Therefore it was concluded that ticlopidine was effective in preventing the grafts occulusion. In the treated dogs, platelet layer was observed only sporadicaly on the boundary between neo-intima and the graft, without the deposition of fibrin network. Significant effect of ticlopidine was also recognized on the prevention of platelet aggregation. These results suggest that the administration of ticlopidine is apparently useful for the vascular prosthesis implantation to arteriola.
Rate output curve was studied in patients with chronically implanted rate programmable pacemakers at rest and after exercise. The following conclusions can be resulted from observation on the rate output curve: 1. In “peaked type” it showed peaked type after exercise. 2. In “flat type” the heart rate on maximum cardiac output after exercise was higher than it was at rest. 3. In the case of patients spending active daily life, it is desirable adjust the pacing rate at the optimal one.
Output-terminal programmable pacemakers have been implanted in three patients of SSS. This pacemaker has two output terminals, one for atrial and the other for ventricular electrode. The termianls are exchangeable each other by a programmer applied outside of the body. Two patients have continued to maintain satisfactory atrial pacing. The remaining one patient temporarily required programming from atrial to ventricular pacing because of transient high threshold with atrial electrode. The output-terminal programmable pacemaker is also advantageous in managing other problems such as atrial fibrillation and atrioventricular block which may develop during atrial pacing.
During the period of September, 1977 to October, 1980, we implanted 145 pacemakers to 140 patients. Among them, 124 patients were programmable. There has been some tendency by economical reason that programmable is not always necessory if preoperative evaluation was sufficiently performed. We have changed the pacing rate in 33, the out put in 17, the sensitivity in 5 and hystersis in also 5 patients. In changing of the pacing rate, the out put and the sensitivity, the programmer was frequently used and it was clinically important. All who were paced by the atrium were temporarily changed in the pacing rate for the follow up of atrioventricular conduction. We consider that it is desirable to implant the programmable pacemaker to every patient and should be implanted in physiological pacing.
Since 1974, 159 programmable pulse generator (53 rate only PPG, 106 rate and output PPG) and 72 multiprogrammable pulse generator (MPPG) have been implanted in 165 patients with symptomatic bradyarrhythmia, ranging in age from 9 to 90 years (mean age 64.8). They were classified into 159 VVIP, 68 VVIM, 4 AAIM, following to new classification code (Furman S., 1980). The rate change were performed for the purpose of improvement of hemodynamics, examination and so on. In VVIM, the rate (57.4%), pulse width (4.4%), sensitivity (4.4%), hysteresis (2.9%) were programmed. In AAIM, programmable functions were used to program over two parametors (rate and sensitivity, or rate and pulse width). PPG and MPPG were more useful than non-PPG. MPPG was more helpful than PPG in clinical use.
The patient was a 42 year-old women. She had an easy fatigability and a bradycardiatachycardia attack in 32 years old. Her puls rate decreased into about 30/M in 36 years old. Then, she was implanted a ventricular stimulating pacemaker (Medtronic 5945) under the diagnosis of Sick Sinus Syndrome and transient complete A-V block. After the implantation, however, in spite of administration of digoxine and diuretics, easy fatigability, edema, hepatomegaly and depressed mood were noted. In 40 years old, she had a chance of the exchange of the pacemaker because of the bettery consumption. Then, cardiac catheterization was performed and cardiac out-put was measured by the thermodilution method. After the optimal rate was determined as 80/M, her pacemaker was exchanged by the programmable ventricular stimulating pacemaker (Microlith-P). In spite of increasing of the cardiac out-put following the pacemaker exchange, she was also annoyed by the easy fatigability, edema, hepatomegaly and depressed mood. In 42 years old, DVI (A-V sequential Ventricular Inhibited) pacemaker was implanted exchanging the ventricular stimulating pacemaker. And then, she was recovered from the incurable cardiac failure and the depressed mood.
Perfluorochemical emulsion (Fluosol-DA) was used for priming solution on extracorpore al circulation in calves. Five of 8 calves were surviving in excellent conditions after perfusion. Their growth was normal except one had excessive Fluosol-DA after perfusion compaired with others. There were no remarkable changes in liver function and other laboratory examinations. Foam cells in the liver and spleen were found reduced gradually in the course of time and most of Fluosol-DA was disappeared from organs within one year. Safety limit of Fluosol-DA administration was 10g per kg of body weight retrospectively from these data.
In regard to cadaveric organ transplantation in Japan, it is impossible to remove organs from beating heart cadaver for transplantation. Therefore, it is mandatory wait untill the heart stops beating at all. This accounts for prolonged warm ischemic time. Organs which are subject to long hypoxia such as liver and pancreas are not being able to tolerate transplantation. We have been reporting our new method of transplantating cadaveric kidney by perfusing in situ, and experimented good results. In order to apply this methods for transplantation of liver and pancreas. We perfused 28 mongrel dogs using of artificial blood substants (Fluosol-DA). Perfusion status and histrogic changes of the liver and pancreas after 6-hour perfusion were examined and following results were obtained. 1) Histological changes of liver and pancreas were little when they were perfused within 30 minutes after heart beating stoped. 2) PFC was not accumulated in pancreas tissue, but it was accumulated in hepatic tissure a little by perfusion.
Normothermic renal preservation had been impossible to achive for periods longer than 4-6 hours. However, advent of perfluorochemical emulsions has opened the possibility of long term normothermic perfusion without any red blood cells in the perfusate for the transport of the oxygen and carbon dioxide. Thirty-one mongrel dogs weighing around 10Kg were used. The right kidney was removed and inserted into a perfusion circuit consisting of a pulsatile pump, an oxygenator, a heat exchanger and a reservoir. Three different kinds of perfusion medium, 20%-FDA, 15%-FDA and 15%-FDA+Calf Serum were used. For the simple evaluation of the perfusion medium, we employed the perfusion time T90, duration from the beginning to the time when the renal vascular resistance exceeded the value of 90 [mmHg·g kidney·min/mL]. The simple dilution to the 15%-FDA provided marked improvement in preservation period, T90=9.18 [h]. And addition of calf serum to the 15%-FDA extended T90 slightly more than that of 15%-FDA, but not significant.
Experiments were done on 10 mongrel dogs to observe the histological changes of liver, spleen, lung, and kidney after 3-hour cardipulmonary bypass (CPB) by apulsatile pump with fluorocarbon emulsion. Dogs were anesthetized and thorachotomy was done bilaterally, after connected to the circuit, the 3-hour CPB was done. As a priming fluid, fluorocarbon emulsion (Fluosol DA 35% The green cross corporation, Japan) was used instead of homologous blood. After 3-hour CPB, dogs were sacrificed and their tissues were fixed with 10% formalin and stained bi Hematoxylin-Eosin stain or PAS stain. Histological changes in the liver were most remarkable. Vacuoles wich were not stained by neither stain were seen in hepatocytes or Kupffer's cells. Sinusoid was slightly enlarged but no necritic changes were seen. Monocytes in spleen contained fine granules or small vacuoles. In the lung, alveolar walls were slightly edematous and kidney maintained it's microstructure. These findings were similar to the findings after 2 days of exchange transfusionwith fluorocarbon to rats and monkeys.
The effects of recirculating single pass operation of dialysate suply on dialysis performance were investigated experimentally and theoretically for effective use of presentday dialyzers. First, relationship between KA and QD for some commercial dialyzers were examined in vitro for determination of solute removal behavior due to dialysate recirculation. Next, the amount of recirculating dialysate is responsible for the decrease of drivingforce between blood and dialysate concentration. this fact can be explained theoretically with our 3pool model presented earlier. Third, relatively large molecule substances are removed more efficiently in RSP than in SP. The in vivo results in Recirculating Single Pass Operation using hollow fiber dialyzers were found to be well explained with our 3pool model. The chemical engineering techniques are effective enough for understanding the clinical conditions of a renal failure patient.
Hemodialysis treatment has been applied for chronic renal failure patients for more than 10 years. The composition of dialysate bas been changed a little for these 10 years but great changes of the dialysate composition could not done because of single dialysate compartment. It is necessary and useful for the advance of dialysis efficiency to increase compartments of dialysate and blood and to realize multi-compartments, multi-dialysate dialysis system. As the first step towards multi—compartment dialysis we tried to add some substances such as bicarbonate, glucose, potassium and sodium to basic dialysate at just before dialyser. It is very easy to make bicarbonate dialysis in this adding system and dialysate composition is stable during dialysis and no precipitation. Tis adding system is very useful and easy to realize high sodium dialysis, sodium gradient dialysis, high potassium dialysis, and low or high glucose dialysis.
An approach intended to prevent HD-induced symptoms is described. This method called ‘PRODIS’ (Programmed Dialysis) is characterized by enhancing the dialysis effeciency gradually during dialysis in order to avoid osmotic imbalance over the body fluid. A one-pool model of the patient-hemodialyzer model is used to ensure the same total removal amount as compared with conventional dialysis. The application of an automated device has prevented the disequlibrium syndrome such as headache and hypotention remarkably. A parameter representing ultra-filtration-compensating ratio (UFCR) was introduced to show that an increase in the UFCR due to PRODIS is effective in preventing hypotention.
A multipurpose ultrafiltration cotrol system which is applicable to simple ultrafiltration during hemodialysis, hemofiltration and hemodiafiltration is devised. Functional principle of the system is that a dialysate flow rate coming in and out of a dialyzer is strictry.controlled by two piston-type equiquantitative pumps in a closed dialysate line while a ultrafiltrate is measured as an overflowed amount in an open line, which then works as an indicater for regulating ultrafiltration pressure. In vitro and clinical evaluation reveals that the system functions satisfactorily in widerange of water removed.
We have recently developed the SND system with a safety air trup chamber and hemonipper due to the ideas that (1) total blood volume in a dialyser should be same as in DND system, and (2) both volume and occasion of the blood recirculation should be as minimum as possible. In this paper, the feasibility of the SND system for the long term hemodialysis in two patients was studied in comparison with an ordinary SND system. 5hr dialysis for our SND system was applied owing to the pre-experimental result that 5hr hemodialysis was sufficient enough for its performance, compared with 7-8hr (6hr, in this paper) dialysis necessary for the ordinary SND system. Other experimental conditions were the same as were applied to the ordinary SND. Compared with the ordinary SND, our SND revealed, in spite of 1hr shorter dialysis, that (a) in both patients the average of the initial BUN and creatinie levels were 10% lower, (b) CTR was also 5% lower and (c) hematocrit was conspicuously increased especially in one patient. The increase of hematocrit may result from the reduction of the negative blood pressure, one of the important improvements in our SND system, in the blood lines. The reasons why our SND system do function so well may reside in the realization of the ideas (1) and (2). This feature will be also explained briefly in this paper.