The present paper deals with the analysis of the blood flow around hollow fibers in a membrane oxygenator. Thrombus formation and performance of a membrane lung are under the influence of hydrodynamic effect. Therefore a quantitative analysis on the behavior of the blood flow inside the membrane lung is needed to develop membrane lungs. In particular, the blood cell movements are important. We measured the blood flow inside the membrane lung using a velocity vector measurement system by visualization of red blood cells about 1.5-3mm on a 14-inch TV monitor magnified 400 times by CCD microscope. The method of the determination of velocity vector is a two-dimensional correlation technique of binary video data. Three ex-viva tests were conducted. The results are as follows. There are high Ht. areas in a membrane lung. There is a relation between these areas and blood clotting areas. Blood flows along hollow fibers, where blood flows parallel to hollow fibers. The stream line around a hollow fiber shows the two dimensional potential flow of incompressible flow. The results of the analysis are applied to the development of a membrane lung.

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Hemoconcentrator is an essential instrument for open heart surgery without blood transfusion. For simplifying the extracorporeal blood circuit and for an easy handling of cardiopulmonary bypass, we have developed a new membrane oxygenator with a function of hemoconcentrator by coupling a hollow-fiber unit for gas exchange and that for hemofiltration in one component. In a cylindrical housing, a set of hollow-fiber for hemofiltration was incorporated longitudinally, and outside of it, another set of hollow-fiber for gas exchange was located. Both of these units employed the blood outside perfusion system, and these were connected in series. Blood enters and flows through the central lumen for hemofiltration and then flows into the oxygenator. With adjusting the flow mode into the module by rearranging hollow-fibers to avoid mutual drag, improved performance was developed by increasing effective surface area. Oxygen transfer rate was 336ml/min at a flow rate of 6L/min, and ultrafiltration rate was 6.2L/hour with a flow rate of 4L/min with a hematocrit of 25%. No adverse effects were identified by coupling procedures. In conclusion, with coupling an oxygenator and a hemoconcen-trator, excellent and simplified hemoconcentration is readily available with this oxygenator due to the blood outside flow mode, which is also one of unique aspects of this device.

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When a membrane oxygenator is used in a liquid-liquid system, entrainment of oxygen bubbles and cell damage caused by the direct contact with the bubbles are eliminated. Enhancement of oxygen transfer rate may give high performance to the membrane oxygenator with high safety. Oxygen transfer experiments were made to determine the oxygen transfer rate of a dialyzer (S. SP-1.5H:Senko Medical Instrument Mfg.) composed of Cuprophan membrane used as a membrane oxygenator. Water, stroma free hemoglobin (SFH) and perfluorooctyl-bromide (PFOB) for gas carriers were used to transfer enough oxygen to water and bovine blood. When PFOB was caused to flow inside the hollow and then the blood outside, oxygen transfer rate was ade-quate. No leak of hydrophobic PFOB to the blood was further observed using hydrophilic membranes.

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The alteration of coagulation and fibrinolysis after open heart surgery under cardiopulmonary bypass were studied by means of “Molecular Markers” . The regulatory or suppressive effect of Nafamostat Mesilate was also examine. Blood samples were taken in 19 patients before 1, 2, 3 and 7 days after surgery. Measured markers were; fibrinogen, antitrombin III thrombin-antlthrombin III complex, FDP, DD dimer, plasminogen, alpha2-plasmin inhibitor and plasmin-alpha2-plasmin inhibitor complex. Data showed that 1)coagulation and fibrinolysis were activated and sustained even 7 days after surgery. 2)Nafamostat Mesilate, when administered after surgery had minimal effect on the activation.

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We studied clinical availability of the newly developed low volume type hollow fiber membrane oxygenator, “CAPIOX-SX” (priming volume 270ml), and compared the performance of the oxygenator with that of “CAPIOX-E (500ml)”. They were applied to 20 patients in CABG (SX:5 patients, E:15 patients). In gas transfer capacity, though FiO₂ during CPB in use of CAPIOX-SX was kept in slight higher level than in use of CAPIOX-E, CAPIOX-SX had enough oxygene uptake capacity, because the gas transfer performance is better in spite of smaller membrane area (1.8m²) than that of CAPIOX-E. Carbon dioxide elimination capacity of CAPIOX-SX was also almost equal to that of CAPIOX-E. Thus, in using CAPIOX-SX the total priming volume was able to be reduced to 1000ml and good gas performance was obtained. Our results showed that CAPIOX-SX is safe and useful to increase the cases of open heart surgery without homologous blood transfusion.

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CAPIOX SX is new extracapillary blood flow type hollow fiber membrane oxygenator. We clinically evaluated CAPIOX SX in comparison wi rh CML EXCEL. Seventeen patlents who underwent elective coronary artery bypass grafting were devided into two groups, CAPIOX SX group (group CS: 6 patients) and CML EXCEL group (group CE: 11 patients). In this study, age, sex, we fight, body surface area (BSA), cardiopulmonary bypass (CPB) time and aortic clamping time were analyzed, and there were no significant differences between two groups. Blood samples were collected 5 minutes before and after the initiation of CPB, then every 30 minutes during CPB. The parameters of gas exchange capability was good, when it was used CAPIOX SX. Furthermore, platelet count and plasma free hemoglobin were measured. Platelet count was mathematically corrected for hemodilut ion. Corrected platelet count in group CE was lower than that in proupCS. The plasma free hemoglobin tended to be lower in group CS than that in group CE part i cul ary differences in two groups were gradually increased after 60 minutes during CPB. In conclusion, this new membrane oxygenator (CAPIOX SX) seemed to have low plasma free hemoglobin, because of the construction of the membrane, which might be explained that flow was more smooth in this new oxygenator.

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Newly developed membrane oxygenator Capiox SX (Terumo, Co., Japan) was clinically evaluated in terms of gas exchange performance and operability. 18 cases were subjected to cardiopulmonary bypass using Capiox SX for various cardiac lesions and surgical procedures. In the first 6 cases, oxygen and carbon dioxide transfer performance were evaluated by effective lung blood flow ratio (Qp/Qt) and CO₂ gradient;CO₂ tension ratio (dCO₂/PaCO₂), respectively. Both indices showed that Capiox SX had an excellent gas exchange performance equal or even better than Capiox II 54 artificial lung. The heat exchange performance was also revealed to be excellent. We concluded that Capiox SX is one of the suitable artificial lungs for clinical application.

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Fifty patients having open heart surgery were intraoperatively and postoperatively analyzed for endotoxin and β-D-glucan. The Toxicolor and Endspecy test methods were used for reading the reactions of endotoxin and β-D-glucan with Limulus amoedocyte lysate. Endotoxin concentrations were in low level and stable during cardiopulumonary bypass, but the values of priming fluids were high exceeding with a maximum of 58.2pg/ml, which probably indicates endotoxin release from the priming fluids. After the start of bypass, the plasma concentration of endotoxic substances including β-D-glucan rose progressively with to a mean value of 221.8 +/- 81.9 pg/ml. The peak value of β-D-glucan was 212.4 +/- 51.8 pg/ml at the end of cardiopulumonary bypass. The changes of β-D-glucan during surgery were correlated with those of α2-plasmin inhibitor-plasmin complex.

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We assessed the liver function during cardiopulmonary bypass (CPB) by measuring the arterial ketone body ratio(AKBR) in open heart surgery. At the begining of the CPB the AKBR decreased significantly. Then the decrease continued for 10 minutes. At the initiation of CPB the initial drop was present. Thease observed changes in the AKBR may be caused by the initial drop.To examine the hypothesis, we studied the portal blood flow of the dogs during CPB, and observed the significant decrease. We concluded that hepatic ischemia induced by CPB appeared for only 10 minutes after the initiation of the CPB, and the AKBR is good indicator for hepatic hypoperfusion during CPB.

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We mesured the arterial ketone body ratio (AKBR) in 31 patients before, during and after CPB and studied the significance of the mesurements.There was the significant correlation between AKBR and lactic-pyruvic ratio(L/P). AKBR showed minimal values just before the end of CPB and changed more quickly than LIP which showed maximal values just after the admission to ICU. It is therefore suggested that AKBR determines the quantity of increased anaerobic metabolism during and after CPB more quickly than L/P. 31 patients were divided into group 1(an AKBR value was less than 0.2 on the just before CPB) and group 2 (an AKBR value was more than 0.2 on the just before CPB). Mixed venous oxygen saturation and LVSWI were significantly lowerin group 1 than in group 2. The difference of the temperature was significantly higher in group 1 than in group 2. AKBR during CPB appear to be useful parameters for predicting the evaluation of hemodynamics state after CPB.

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We measured the changes in arterial ketone body ratio in response to 75-g oral glucose loading to determine the mitochondrial ability in 23 preoperative patients with open heart surgery. The redox tolerance index (RTI) represents a 100-fold cumulative enhancement of ketone body ratio relative to glucose level (100×ΔA AKBR/Δglucose). Subjects were divided into two groups(I: RTI ≤0.8, II: RTI>0.8). Postoperative total bil irubin level was significantly high in group I (p<0.05). Postoperative serum GOT level was also high in group I. The recovery of AKBR in group I after cardiopulmonary bypass was slower than in group II. This study shows that RTI based on redox theory is helpful in postoperative care in patients who underwent cardiopulmonary bypass.

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The newly developed Nikkiso HMS-15 is a minimally sized centrifugal pump. It has an impeller diameter of only 50mm, priming volume of only 25ml, and weighs only 145 g. The in-vitro and in-vivo testings of hemolysis have already been done, and the pump showed the same or even lower amount of hemolysis than other commercially available centrifugal pumps. This study tested the amount of blood trauma when applying it as a pump for cardiopulmonary bypass (CPB) in open heart operations. 9 patients using Nikkiso HMS-15 and 10 patients using conventional roller pumps were compared. 10 preoperatve, operative, and post-operative measurements were performed. The increase of plasma hemoglobin, LDH, and granulocyte elastase, and the decrease of haptoglobin, α₁-antitrypsin, and platelet counts during CPB, and their recovery did not show any difference between the two groups. It was concluded that the degree of blood trauma of the HMS-15 is the same as the roller pumps, and this pump is well acceptable for clinical usage.

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The aim of this study was to evaluate the hepatic grafts procured by selective abdominal organ perfusion using cardiopulmonary bypass with hypothermic blood and to determine the potential of this procedure. Five female pigs, weighing 20kg, were used in this study. After ligation of the abdominal aorta and the inferior versa cava at the level of diaphragm, abdominal organs were perfused with normothermic blood to maintain a rectal temperature of 36°C (Group I) and hypothermic blood to maintain a rectal temperature of 28°C (Group II) for one hour. During perfusion, portal blood flow, hepatic oxgen delivery and AKBR of the Group II were significantly higher than those of the Group I, while there were no significant differences in hepatic arterial bood flow and oxgen consumption during perfusion. The GOT and GPT value of the Group II were significantly lower than those of the Group I after transplantation. But no animal survived for over 12 hours in either group. These results suggest that this method of hepatic graft procurement using cardiopulmonary bypass with hypothermic blood may remain viable if hepatic oxygen consumption can be decreased and the decreasing of hepatic oxgen delivery can be prevented during perfusion.

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We have undertaken an experimental study to evaluate cerebral tissue damage after retrograde cerebral perfusion (RCP). Ten mongrel dogs weighing 10 to 15 kg were used for this study. Conventional cardiopulmonary bypass (CPB) was established, with cooling to a nasopharyngeal temperature of 20°C. RCP was then performed with blood perfusion through the bilateral maxillaly veins at a flow rate of 150 to 250 ml/min, After the 120 min of RCP, CPB was restarted with rewarmin Cerebral metabolic rate of oxygen (CMRO₂), cerebral metabolic rate of glucose (CMRGIu) and cerebral blood flow(CBF) did not worsen during RCP. Intracranial pressure (ICP) did not increase by the end of RCP. However, in dogs those were not given mannitol ICP showed marked increase 30 min after CPB was restarted (23.2±7.7 mmHg), whereas in dogs given mannitol prior to reperfusion ICP did not show abnormal increase after CPB was restarted (8.4 ±3.4 mmHg). Water content of the brain tissue in dogs administered mannitol (74.95 ±0.58%) was signifficantly lower than that in dogs without mannitol (77.29 ±0.33%). In conclusion cerebral metabolism was maintained during the 120 minutes of RCP, but brain edema should develop after the reperfusion of antegrade cerebral blood flow. Administration of mannitol prior to reperfusion could enhance neuronal recovery.

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We introduced a new cardiopulmonary bypass system which was developed in the veterinary field for small animals into cardiovascular research. This system was produced very compactly. It was available for use in animals weighing from 2 to 50 kg. This circuit was adopted using a semi-closed circulation type with a sheet-reservoir. We could reduce the minimum priming volume to 169ml, which was about a quarter of the circuit priming volume for an infant. It will be very useful for recovery of small animals after open heart surgeries with this system.

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For easy and safe management of cardiopulmonary bypass (CPB), CPB support system was developed using personal computer. The software of this system consists of the block for preparation of CPB, one for operation of CPB, one for printing of patient data and one for the network to other computer systems. As the hardware, PC-386LS(EPSON)personal computer was used. Sound synthesis board was used for output of sound synthesis and A/D converter for input of patient's circulatory data. This CPB support system was used to 478 cases of open heart surgery. The operation of this system did not bother pump technicians and other staffs. Alarm system for the pressure(perfusion pressure, blood pressure, PA pressure, CVP etc.)and for the patient data (blood gas analysis, Hb, Ht, Na, K, Cl, Blood glucose, ACT etc.)was very helpful. Time duration(perfusion time, aortic clamp time and infusion time of cardioplegic solution), and temperature(perfusion blood temp. of inlet&outlet, esophageal&rectal temp.)were displayed in real time. In-out balance, urine volume per hours, systemic vascular resistance and complete rewarming time were calculated at any moment.
This system made the preparation of CPB easy, and the operation of CPB safe. In conclusion, , this support system was very useful for management of CPB.

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Forthe purpose of circulatory and respiratory suport, we employed heparin-coated ECMO(CBAS-ECMO) system for 5 cases.All cases were weaned from ECMO and survived except for one case, who died from respiratory failure 37 days after ECMO removal.As complications during ECMO, generalized edema and jaundice was noted in one case, and oxygenator failure in two cases.There was neither significant hemorrahge nor systemic thromboembolism. For the short-term use of this CBAS-ECMO system, changes of platelets counts, coagulation and fibrinolysis were minimal and circuits thrombus was not detected.But in the prolonged cases, small thrombi weredetected at stagnant zone of artificial lungs. From these results, we conclude that CBAS-ECMO system has superior biocompatibility but that durability of artificial lung and decrease of antithrombogenicity during the long-term use must be improved.

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We studied the blood compatibility of heparin-coated cardiopulmonary bypass circuits compared with noncoated circuits. In four patients undergoing coronary bypass, the heparin-coated circuits were used (group1), and three served as control patients (group 2). The concentration of factorXIII, fibronectin, ATIII, total protein and albumin were measured before operation, one hour after starting the pump, at the time of entering ICU, 1st postoperative day(POD), 3rd POD, 7th POD and 14th POD. All of these parameters except fibronectin were higher in group 1 compared with those in group 2 after operation. In group 1, especially total protein showed significantly (p<0.05) higher than in group 2 at the time of entering ICU, 7th POD and 14th POD. This result indicated that heparin coating of the circuit had the possibility of inhibiting the deposition of total protein to the luminal surface of the circuit device. As the deposition of protein to cardiopulmonary bypass circuit is correlated with perioperative activation of complement, leucocyte and platelet, it was concluded that the heparin-coating of the cardiopulmonary bypass circuit improved blood compatibility of the circuit device.

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To clarify the efficacy of the heparin-coated cardio-pulmonary bypass system incorporating with low-dose heparinazation, blood-material interactions in a standard open-heart surgery were examined. Two groups (heparin-coated system group; n=7, initial dose=2mg/kg and additional dose=1mg/kg, non-coated system group; n=7, initial dose=3mg/kg) were compared each other with several items. There was no difference in the rate of thrombin formation (reflected in thrombin-antithrombin III complex) during the cardio-pulmonary bypass despite the significant difference in heparin concentration between the groups. Platelet (count, beta-TG, aggregation rate) and complement (C3a) activation during the bypass tended to be more prominent in the non-coated group. Red cell deformability, which was assessed with red cell filtration rate, was significantly better in the heparin-coated group. We conclude that usefulness of the heparin-coated cardiopulmonary bypass system is preserved even under the low-dose heparinization in the standard open-heart surgery.

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To evaluate the antithrombogenecity and the performance of the oxygenator in the totally heparin-coated cardiopulmonary bypass system, veno-venous extracorporeal membrane oxygenation (ECMO) was performed in a canine model. This system consisted of 2.0m²hollow-fiber membrane oxygenator, a newly developed centrifugal pump, thin wall cannulae designed for percutaneous insertion. No reservoir was used. In coated group (n=6), the blood contacting surface of all system was coated with covalentiy binding heparin and ECMO was done without systemic heparinization. In non-coated group (n=6), the system without heparin-coating was used and ECMO was done under systemic heparinization (300Units/kg). In both groups, ECMO was performed for 12 hrs. To mimic a critically severe condition for testing the antithrombogenecity, the bypass flow was limited to 500 ml/min. throughout the study. There were no differences in gas exchange and platelet function between the two groups. There was no major macroscopic thrombus formation in the coated group even under low-flow bypass without systemic heparinization. These results suggest that this heparin-coated system can be an avenue to realize the long-term heparinless ECMO.

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We have reporte that the Vibrating Flow Pump (VFP) give the good gas exchange efficiency to the membrane oxygenator, when the VFPwas applied as the pump for Extracorporeal circulation (ECC) in animal experiments. In this paper, 6 adult gouts were anesthetized by halothane ^R. The incision was carried through the fascia of the neck, and left common cervical vein was exposed, via this vein inflow cannula was inserted for right atrium. After that, the transverse skin incision across the breast on the left side of goat, and outflow cannula was inserted main trunk of pulmonary artery. After extracorporeal membrane oxygenator (ECMO) circuit was set, respirator was stopped, several minutes later, ECMO was started using VFP with the driving frequency 20Hz. ECMO blood flow was kept about 10-20ml/min/Kg, FiO₂: 1.0, O₂: 3 1/min. The effect of ECMO using VFP was evaluated blood gas analysis and hemodynamics. During ECMO, PaO₂was maintained about 100-150 torr and PaCO₂: 35-45 torr. No remarkable change was given to the goat by ECMO using VFP. This result shows that the ECMO using vibrating flow pump is very useful for respiratory distres syndrome.

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Severe cyanotic neonates with complex heart disease or diaphragmatic hernia may require the emergency operation under progressing acidosis caused by hypoxia. ECMO will be one of useful devices to manage this critical stage at/after operation. However, these procedure require many surgical staffs, time and skill. Therefore, we devised a new type of intravenous oxygenator for neonate to manage these critical patients quickly with simple technique. Our device is made of 100 polyolefin fibers with oxygen inlet and outlet port. It is inserted via jugular vein to the IVC with use of guiding catheter. Its maximum diameter is 3.5mm. At first we evaluated this device on experimental circuit, then we implanted it in the 5 child dogs. In the experimental circuit study, we found this device increased oxygen transfer under increased blood flow and decreased blood oxygen saturation in circuit. In the animal study, the change of oxygen saturation in the pulmonary artery became large because the saturation in the femoral artery and vein was also increased. The added oxygen reached to about 1ml/kg/min when the venous blood saturation was 20%. Our equipment has low ability of adding oxygen, however, we think it will be useful under the condition of progressing acidosis due to hypoxia.

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We developed a new automatically driven blood pump for neonatal extracorporeal membrane oxygenation circuit. Our blood pumps consisted of a pair of sac-typed air driven blood pumps with LED sensors, which are controlled with three types of pumping mode. A-mode: the output was as same as the intake meeting the Starling's law, B-mode: the output was modified by delaying compression of the blood chambers after they filled, and C-mode: the blood pumps kept a constant output by applying positive or negative pressure on the air chambers regardless of the resistence at both the inflow and outflow. These characteristics of each mode were demonstrated on a mock circulation. Our experiment suggests the usefulness combining these modes for neonatal ECMO, and makes all of ECMO course automatically controlled and safely operated starting and maintaining with A-mode and B-mode, and weaning performed with C-mode.

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The weaning from cardiopulmonary bypass (CPB) is a very critical stage of cardiac surgical procedures. In this stage, it is necessary that we can assess cardiac function instantly and quantitatively. We continuously monitored coronary sinus blood oxygen saturation (CS-SvO2) from release of aortic cross-clamp till 5 minutes after CPB, in eighteen patients undergoing cardiac surgery. We studied correlation among CS-SvO2 and cardiac function, myocardial metabolic products. Significant positive correlation was observed between CS-5vO2 of 15 minutes after aortic unclamping and cardiac index of immediately after CPB. Significant negative correlation was observed between CS-SvO2 of 15 minutes after aortic unclamping and anaerobic myocardial metabolic products of 5 minutes after CPB. We concluded that CS-SvO2 of 15 minutes after aortic unclamping was useful to assess cardiac function and myocardial metabolic state.

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The blood perfusion of systemic circulation is influenced by the physical characteristics of artery. Several investigations proposed that the physical parameters of vessels are determined by some factors which are neurological factors, hormonal factors, physical properties of artery and so on. In this study, the arterial impedance was estimated because it may express the conditions of vessels. To examine the change of arterial impedance according to the blood flow pattern, the typical sine-wave blood flow, which was called oscillated flow, was used for the total cardiopulmonary bypass (CPB), because it can be considered for the most simple pulsatile flow. CPB using oscillated blood flow was performed for eight adult goats in acute experiments. The total systemic flow were controlled to maintain about 80ml/min. Aortic pressure, central venous pressure and systemic flow were measured. And the total peripheral resistance and arterial impedance were calculated to evaluate the reaction of vessels during the CPB. From this study, it was shown that arterial impedance was fluctuated according to the change of flow frequency. So the vascular reaction to the change of blood flow velocity might be characterized during oscillated blood flow.

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A new cardio-pulmonary bypass (CPB) system for small animals was developed. Reconstruction of right ventricular outflow tract with biological grafts and atria septa_ defect patch closures etc. were performed under the CPB system in eleven dogs (BW;4.5-11.8kg). Aortic cross clamping time was 20-77 min (35±16 min; mean±S.D.). Total CPB time was 43-168 min(85±38 min). The weavings from CPB in all dogs were performed without any difficulties. Blood transfusion was required in 4 out of 11 dogs after operation. Although it has been previously difficult for small dogs to survive after undergoing CPB procedures, we were able to obtain successful long term results (max 1 year) by using our new CPB system.

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We use two type of membrane oxygenator in adult with open heart surgery. Group 1(n=9):silicone hollow fiber oxygenator, Group 2 (n=11):polypropylene hollow fiber oxygenator. Using these oxygenator we compared platelet count(PLT), polymorphonuclear elastase(PMNE) and alpha 1-antitrypsine(A1-AT) during and post operation. And respiratory function and hemodynamic status were also measured post operation. The results were as follows: 1.The platelet count was higher in group 1. 2.PMNE activity was lower in group 2 and A1-AT was significantly higher in group1. 3.The recovery of the oxygenation index, which was used for evaluation of the respiratory function, was better in group 1. 4.The period of using catecholamine was shorter in group1.

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We have developed a new system for warm blood cardioplegia consists of recirculating circuit with a membrane lung(Silox-S), and applied to aortic valve surgery as terminal warm blood cardioplegia(TCP) for 15 minutes. The pH, base excess, hematocrit, and K⁺of perfusate showed no significant changes during TCP. The myocardial lactate extraction ratio and excess lactate showed positive and negative values during TCP, respectively. The 67% of TCP group obtained a spontaneous heart beat after TCP. These results suggest that this new system is safe and steady method for warm blood cardioplegia.

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