[Surgical case of mediastinal lymphangioma with subclavian anomaly].
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Biomedical subjects
Publications and source records attributed to H Takano.
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The mF plasmid which promotes mitochondrial fusion in Physarum polycephalum is a linear molecule with complex terminal inverted repeats (TIRs). Its nucleotide sequence was determined. The mF plasmid is 14,503 bp in size, and contains ten open reading frames (ORFs). All of the ORFs except one are encoded on the same DNA strand (coding strand). The number of amino-acid residues in the putative proteins derived from the nine ORFs on the coding strand are 231, 163, 640, 235, 118, 1130, 366, 309, and 547 from left (5' end) to right (3' end) on the map. The amino-acid sequences of newly-identified ORFs on the mF plasmid did not show significant homology to any amino-acid sequences in the databases. A brief transcriptional map of the mF plasmid was constructed, and the following features were noted. (1) The transcription initiation site was located just inside the end of the left TIRs, but not within the TIRs themselves. (2) Three major transcripts of 1.0, 3.4 and 4.6 knt corresponded to the left region of the mF plasmid, and long, low-abundance (more than 4.6 knt), heterogenous transcripts corresponded to almost the entire mF plasmid. A low-abundance, 3.5-knt transcript corresponding to the coding region of ORF1 130 (a 1 130-amino-acid polypeptide) was also detected, and may be derived from the long transcripts. (3) The quantity of transcripts which included the region near the transcription initiation site was about 500-times more than that which included the region near the inner end of the right TIRs.
The talonavicular relationship in 14 patients with talipes equinovarus was quantified using gradient echo sequences. The angle formed between the short axis of the navicular and the long axis of the talus was measured. There is a significant difference in the talonavicular angle between patients who had posteromedial release (PMR) and those who had posterior release (PR) or casting only (P=.0004). This method provides an objective assessment of residual deformity following surgical and conservative management of talipes equinovarus.
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A left ventricular assist device (VAD) with a smooth surface of segmented polyurethane was implanted in five goats for 10-55 days, and plasma levels of fibrinogen (Fg), prekallikrein (PK), fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), partial thromboplastin time (PTT), platelet (Pl) count, and platelet aggregation (PlAg) induced by adenosine diphosphate were measured during the experiment. Heparin was administered during surgery and no systemic antithrombotic therapy was given thereafter. Before the third postoperative day (POD), plasma levels of Fg and PK were at their lowest, and increased afterward. Between the second and fifth POD PT and PTT increased to 130-160%, and returned to normal gradually. Plasma FDP appeared on the second POD and reached peak values of 10-40 micrograms/ml on the sixth POD. Platelet and AT III levels showed no uniform tendency, but the rate of PlAg decreased to levels of 6-77% before the fifth POD and remained low at approximately 80%, influenced by the pumping even after the 25th POD. In summary, VADs themselves activated coagulation and induced consumption coagulopathy to some degree. However, most of the parameters returned to normal within 2 weeks.
Regulatory mechanisms of coronary circulation during left ventricular assist (LVA) were studied in chronic experiments using adult goats. In normal heart studies (n = 3), circumflex coronary artery flow (CxF) and endocardial blood flow (MBF) decreased in proportion to decrease of tension time index (TTI). Mean CxF/TTI was constant at 0.22, whether the LVA functioned or not. In the left anterior descending branch ligation model (AMI) study (n = 2), CxF decreased according to decrease of TTI throughout the experiment, if the bypass ratio was kept within a normal range of systemic pressure. Mean CxF/TTI was maintained at approximately 0.21 by LVA, fell to 0.16 when LVA was turned off during the early stages. Coronary circulation during LVA was regulated by oxygen demand if systemic circulation was maintained, and LVA improved oxygen demand-supply balance in failing hearts.
An electrohydraulic ventricular assist system with a linear actuator was developed, and in vitro and in vivo evaluations were performed. During in vitro evaluations this system could yield 5.6 L/min of pump flow against a mean afterload of 100 mmHg. Durability tests were performed for more than 4 months. The system was implanted in three goats and a maximum pump flow of 4.2 L/min was obtained against a mean afterload of 100 mmHg, and 3.2 L/min against 130 mmHg. These evaluations have proven that the system can maintain stable hemodynamics under various conditions.
A ventricular assist system (VAS) developed at the National Cardiovascular Center (NCVC) and produced by Toyobo Company has been clinically evaluated at 32 institutes. The system consists of a pneumatic and diaphragm-type pump, and a control-drive unit with an automatic bypass flow (BF) control system. The VAS was used in 85 adults and 7 children with acute, severe heart failure. Forty-eight patients were weaned from VAS, and 21 were long-term survivors. Heparin was not used when BF was above 2.0 L/min in an adult sized pump, and 0.8 in a pediatric one. Thrombus formation was noticed in the groove around the valve in eight cases, and in the pump in eight. Pump-originated serious complications were not seen. Hematologic and biochemical findings revealed that the VAS did not directly affect the major organs. The control-drive unit, including the automatic BF control system, functioned accurately, with less manpower, securing reliable control over the circulation. Two major causes of death were irreversible heart failure, and multiple organ failure, which resulted from delayed application. In conclusion, the NCVC-type VAS has been found effective and reliable, less thrombogenic, and requiring less manpower for its clinical use.
A pneumatic pediatric ventricular assist device (VAD) with a stroke volume of 20 ml has been developed to treat post-operative heart failure (HF), and maintain transplant candidates. The polyurethane VAD has two #21 Bjork-Shiley valves and the internal diameter of the cannula is either 6 or 8 mm. Hemodynamic effects of a left ventricular assist device (LVAD) on a HF after Fontan's procedure model, and those of a right ventricular assist device (RVAD) on right HF with pulmonary hypertension model, were investigated in acute experiments with four and five dogs, respectively. In the former, the pressure gradient across the lung and cardiac output (CO) increased with an LVAD; right atrial pressure decreased and CO increased with an RVAD in the latter. The pump was implanted as an LVAD in 8 young goats, 9-22 kg in weight, for 4-10 weeks and favorable in vivo performance was demonstrated. The VAD system was applied as an LVAD to two postcardiotomy patients, a 12 kg boy with a ventricular septal defect, and a 13 kg boy with an endocardial cushion defect. In these cases, CO was well maintained at the level of 2.5-4.1 L/min/m2 for three and seven days, respectively, and the pump was removed. In conclusion, this VAD will become a promising circulatory support system for pediatric uses.
A simplified cannulation system was developed without thoracotomy for a ventricular assist system (VAS) that will be applicable even in an emergency. This system consists of an air driven and diaphragm type pump, cannulae, and devices for insertion. The inlet cannula was inserted into the left atrium through the femoral vein using a modified brockenbrough transseptal method. This system was installed without thoracotomy in a chronic experiment in two goats and was removed without any trouble after 14 days of pumping. In a 40 day experiment with this system implanted between the left atrium and the aorta, bypass flow was maintained at 2.7 to 3.3 L/min, and plasma free hemoglobin levels were below 7 mg/dl. When this system was implanted between the left atrium and the aorta, and activated in an induced heart failure goat, output through the pump was 3.0 +/- 0.4 L/min, and mean aortic pressure was increased to 91.7 +/- 15.9 mmHg from 55.8 +/- 15.4 mmHg. This system takes a middle position between an IABP and VAS with thoracotomy in capability of circulatory support and convenience.
The authors designed a new extracorporeal membrane oxygenation (ECMO) method using a right ventricular assist device (RVAD) system and a membrane oxygenator (MO). An air-driven diaphragm type RVAD was implanted between the right atrium and the pulmonary artery in five goats, and an MO was set on the outlet conduit of the RVAD 2 weeks postoperatively. The MOs used in this study are silicon sheet MOs and prototype MOs using a novel multilayered composite membrane. Respiratory support with this system, under systemic heparinization, could be conducted for 4-8 days without major problems. This method solved several difficulties with ECMO, such as surgical bleeding, serum leakage, destruction of the blood components from the pump system, inadequate bypass flow, and fatal systemic thrombosis. This method is suitable for long-term respiratory support, especially as a bridge before lung or heart-lung transplantation.
The authors have developed a new actuator to drive an electrohydraulic totally implantable artificial heart. The basic concept of this artificial heart is that the blood pumps are implanted in the thorax and an actuator is placed separately in the abdominal region. The actuator is a regenerative pump that pumps fluids against high pressures and is thin enough for easy implantation. The rotor-magnet of the brushless DC motor is mounted on the impeller of the pump to miniaturize the actuator and reduce the number of moving parts. The height, diameter, and weight of the actuator are 32.5 mm, 73 mm, and 360 g, respectively. A pair of oil ports is connected to the left and right blood pumps with mesh reinforced tubes filled with silicone oil. The blood pumps are alternately driven by bidirectional rotation of the motor. Performance of the system was evaluated in in vitro and in vivo experiments. Maximum output of the right heart was 6.7 L/min in both experiments. Systemic circulation was well maintained in acute animal experiments using 49 and 50 kg goats. The feasibility of the actuator was confirmed.
The biocompatibility of the Terumo (Terumo Corporation, Tokyo, Japan) covalent heparin coating method in a cardiopulmonary bypass (CPB) circuit was evaluated in ex vivo and in vivo experiments. In the ex vivo experiment, fresh human heparinized blood primed both a miniature heparin coated circuit (HCC) and the identical noncoated circuit (NCC), and was circulated simultaneously for 2 hr (n = 6). In the in vivo experiment, 10 rabbits underwent 2 hr of CPB under systemic heparinization (ACT > 400 sec) with HCC (n = 5) and with NCC (n = 5). In the ex vivo study, thrombin/anti-thrombin III complex, thromboglobulin, platelet factor IV, granulocyte elastase, and C3a were significantly lower in the HCC than in the NCC at 60 and 120 min of circulation (p < 0.05). In the in vivo study, platelet counts (percent of value at 10 min of CPB) were significantly higher in the HCC than NCC (HCC:NCC 87 +/- 10:71 +/- 12 at 60 min, 81 +/- 17:56 +/- 16 at 120 min). Scanning electron microscopic examination of the circuits showed less significant adhesion and pseudopod formation of platelets in the HCC than NCC in both ex vivo and in vivo situations. These results demonstrate that this heparin coated CPB circuit provides superior biocompatibility compared with a noncoated circuit by reducing the activation of the coagulation cascade, platelets, leukocytes, and complement.
To achieve more physiologically successful cardiopulmonary bypass (CPB), the effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT), were examined in open heart surgery. Thirty adult patients were divided into two groups. In Group F (GpF; n = 15), 2 mg/kg/hr of FUT was administered continuously during CPB and 0.2 mg/kg/hr before and after CPB. FUT was not given to Group C patients (GpC; n = 15), who acted as controls. Serotonin and histamine levels in plasma, platelet counts, platelet adhesive function levels, and alpha 2 plasmin inhibitor-plasmin complexes (PIC) were serially measured. The serotonin level in GpF was significantly lower at 5 min of CPB than in GpC. Histamine levels in GpC decreased remarkably after starting CPB, then later recovered; by contrast, they did not decrease in GpF during CPB. At 1 hr after CPB, platelet counts were higher (p < 0.01) in GpF (54 +/- 8%) than in GpC (41 +/- 10%), and platelet adhesion was lower (p < 0.01) in GpF (7 +/- 7%) than in GpC (34 +/- 13%). The PIC was significantly less in GpF than in GpC throughout the surgery. Blood loss in GpF was significantly reduced compared with that in GpC. In conclusion, FUT attenuated chemical mediator reactions, such as plasma serotonin and histamine, and also reduced blood loss by preserving platelets and inhibiting fibrinolysis during CPB.
This study was designed to investigate the permeation of silicone oil through a pump diaphragm made of Pellethane in the authors' electrohydraulic ventricular assist system (EHVAS) and to evaluate influences on organ function. The permeability of the diaphragm to silicone oil was investigated by in vitro experiments. Influences on organ function were evaluated in five goats with an EHVAS by monitoring serum silicon levels (SSi), blood chemical parameters, and histologic findings. Elevation of silicone oil levels in Pellethane sheets immersed in silicone oil demonstrated that the Pellethane diaphragm was, in fact, permeable to silicone oil. The permeation rate of silicone oil was calculated to be 1.75 ml/year in the authors' EHVAS from the data of a diffusion apparatus test. Serum silicon levels did not increase during the EHVAS pumping, and renal and hepatic function were not affected. No abnormality or deposit suggestive of silicone oil was observed. However, the problem of permeation of silicone oil through the pump diaphragm must be solved to allow for a circulatory assist device for long-term use.
The authors have been developing an electrohydraulic total artificial heart with a basic concept placing the blood pumps and an electrohydraulic energy converter separately, in the thorax and the abdominal region, respectively, to minimize anatomic constraints. Major problems of the system were a high energy consumption of 56 W at 6 L/min output and an insufficient maximum output of 6.7 L/min. The energy converter was redesigned to overcome these problems. A three phase, 4 pole brushless DC motor, which has maximum efficiency of 79% at a motor rotation of 2500 rpm with a load of 0.1 Nm, was developed for the new energy converter. Flow-channel design of the regenerative oil pump was optimized, which resulted in increasing the maximum flow rate at one directional motor rotation from 18 to 29 L/min. In vitro performance of the electrohydraulic total artificial heart was evaluated in a mock circulation with physiologic pressure conditions. Maximum output was increased to 10.7 L/min at a pump rate of 120 bpm and energy consumption of the motor at 6 L/min output was reduced to 18 W. Based upon these favorable results, the system is now being assembled for chronic animal implantation.
We have developed an implantable pneumatically driven diaphragm left ventricular assist system (LVAS) for small adults, and an electric impedance based monitoring and control system (Z system). In this Z system, measurement of electric impedance of the blood chamber is performed by charging an alternating current with a constant amplitude between two metal connectors without compromising anti-thrombogenicity. Automatic calibration was performed periodically by measuring trough values of impedance in the blood chamber for several beats while the blood pump was in a full-fill state under preset driving conditions. For precise control of the fill-to-empty (F/E) drive, an automatic trigger level adjustment method was developed. This method is an automatic searching algorithm that identifies the volume change of the last ejection or filling by the Z system and settles the next trigger level to maintain a definite stroke volume. In chronic in vivo evaluation, this LVAS was used in 13 adult goats. The pump was installed between the LV apex and the descending aorta and was placed in the abdominal wall. Pump output ranged from 2.5 to 5.8 L/min, and the Z system provided good monitoring. The F/E drive was achieved satisfactorily by this Z system. The physical condition of the goats was excellent for as long as 19 weeks. Hematologic, hepatic, and renal functions were within the normal range, and no prominent thromboembolic symptoms were observed. A new mobile control drive unit with this Z system is being developed. We conclude that this LVAS with the Z system is promising for long-term use in a clinical setting.