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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 595 records · Page 33Linked to original sources

How does the sympathetic nervous system behave during non pulsatile circulation?

Non pulsatile circulation is commonly applied to clinical cardiopulmonary bypass or circulatory assist. However, influences of non pulsatile circulation on sympathetic nerve activity, which plays an important role in circulatory control, have not been elucidated. In this study the renal sympathetic nerve activity (RSNA) was recorded for the first time in goats, whose heart rate and size are similar to humans', and the difference during pulsatile and non pulsatile circulation was evaluated. Total left heart bypass was instituted in eight adult goats under general anesthesia. A pneumatic pulsatile pump and a centrifugal non pulsatile pump were incorporated in parallel so that pulsatile circulation and non pulsatile circulation could be instantly converted to the other. The pumping rate was set at 90/min regardless of the native heart rate during pulsatile circulation and the mean aortic pressure was maintained constant at the conversion of circulatory mode. The original signals of RSNA were integrated and defined as the mean RSNA. The mean RSNA and the mean aortic pressure were averaged every 30 sec and quantified during pulsatile circulation and non pulsatile circulation. The pulse synchronized burst of RSNA during pulsatile circulation immediately disappeared and the mean RSNA significantly increased up to 120% of pre depulsation level after changing the circulatory mode to non pulsatile circulation. Reverse conversion of circulatory mode from non pulsatile circulation to pulsatile circulation decreased the mean RSNA to 79%. The results suggest that vasotonus may be affected in its periodicity as well as its quantity by the loss of pulsation during the initial phase after depulsation.

Animals↗

Long-term circulatory support to promote recovery from profound heart failure.

In profound heart failure, ventricular assist systems (VAS) have been used to maintain the systemic circulation and promote recovery of the failing heart. The authors' data suggest that the heart may not recover sufficiently if the patient needs left ventricular assist beyond 10 days. Recently, the authors treated six patients who were supported by VAS more than 3 weeks and were weaned from VAS. Four of six patients were weaned from VAS and continue well, despite marginal cardiac function. In the other two patients, the natural heart did not sustain stable recovery, but their general conditions made them fit to be candidates for heart transplantation. Based on these data, long-term support should be considered to promote recovery of heart function with the use of VAS for profound heart failure.

Adolescent↗

Long-term cardiopulmonary support with a composite artificial heart-lung system.

A novel cardiopulmonary support (CPS) system as a long-term total substitute for the natural heart and lung was designed and evaluated. The CPS system is composed of a ventricular assist device (VAD) and a newly developed compact artificial lung (AL). The pneumatic VAD was originally developed in the authors' institute and has proven durable and antithrombogenic in over 120 clinical uses. The AL, with 1.2 m2 membrane surface area and 140 ml priming volume, consists of a special gas exchange membrane where not only are micropores blind-ended to prevent serum leakage, but the blood contacting surface is treated with heparin binding to ease systemic anticoagulation. Chronic animal experiments of total CPS were carried out in three goats weighing from 28 to 36 kg. Venoarterial bypass was instituted with the CPS system in which all venous blood was drawn from both the right atrium and ventricle and returned to the aorta. No systemic anticoagulation was conducted except for heparin added fluid infusion from pressure lines. One animal survived for 2 weeks without any device related problems until electively euthanized. Blood flow rate ranged between 3.2 to 4.5 L/min, O2 transfer between 120 to 220 ml/min, and CO2 removal between 60 to 210 ml/min. No substantial changes were found in platelet count or other coagulation factors. These results indicate that the system has the ability to be used for long-term CPS, such as a bridge to lung or heart-lung transplantation.

Animals↗

Set-up, improvement, and evaluation of an electrohydraulic total artificial heart with a separately placed energy converter.

The authors have been developing an electrohydraulic total artificial heart (TAH) system with a separately placed electrohydraulic energy converter to minimize anatomic constraints in the pericardial space. Improvements to the system and current status of the development are reported. The energy converter was miniaturized to improve implantability, and its thickness was reduced to 54 mm. System efficiency was increased by suppressing rush current at the time of motor reversal. Maximum cardiac output of the TAH system was 9 L/min, and maximum system efficiency increased to 10%. The blood pump system was implanted easily in the body of a 57 kg calf, and no significant temperature rise on the energy converter surface was observed. As the next step, main components were integrated into a total system. The transcutaneous energy transfer system could supply power to the TAH without a decline in pump performance, and the internal battery could support the system at 6.5 L/min of cardiac output for 1 hour without a decrease in cardiac output. The authors consider the TAH system with a separately placed energy converter the most promising approach to development of a TAH for smaller sized patients.

Animals↗

Development of a precise controller for an electrohydraulic total artificial heart. Improvement of the motor's dynamic response.

In an electrohydraulic total artificial heart developed at the National Cardiovascular Center (Osaka, Japan), two blood pumps are pushed alternatively by means of the bidirectional motion of a brushless DC motor for pump systole and diastole. Improvement in the dynamic response of the motor is very important to obtain better pump performance; this was accomplished by using power electronic simulation. For the motor to have the desired dynamic response, it must be commutated properly and the damping ratio (zeta), which represents transient characteristics of the motor, must lie between 0.4 and 0.8. Consequently, all satisfactory specifications with respect to power consumption must be obtained. Based on the simulated results, the design criteria were determined and the precise controller designed to reduce torque ripple and motor vibration, and determine motor stop time at every direction change. In in vitro tests, evaluation of the controller and dynamic response of the motor was justified in terms of zeta, power consumption, and motor stop time. The results indicated that the power consumption of the controller and the input power of the motor were decreased by 1.2 and 2.5 W at zeta = 0.6, respectively, compared to the previous system. An acceptable dynamic response of the motor, necessary for the reduction of torque ripple and motor vibration, was obtained between zeta = 0.5 and zeta = 0.7, with an increase in system efficiency from 10% to 12%. The motor stop time required for stable motor reoperation was determined to be over 10 msec, for a savings in power consumption of approximately 1.5 W. Therefore, the improved dynamic response of the motor can contribute to the stability and reliability of the pump.

Biomedical Engineering↗

Influence of non pulsatile systemic circulation on tissue blood flow and oxygen metabolism.

Influence of non pulsatile systemic circulation on oxygen metabolism was examined regarding tissue perfusion in 12 adult goats weighing from 46 to 55 kg. Under general anesthesia, a flow character, changeable total left heart bypass circuit consisting of pulsatile and non pulsatile pumps was installed through a left thoracotomy. Systemic flow was converted from pulsatile to non pulsatile in 7 of 12 animals, and in the reverse order in the other 5, by changing the driving pump. Esophageal mucosal blood flow was determined by a colored microsphere method that estimated tissue blood flow at the pre capillary level. Esophageal intramucosal pH was evaluated with a silicone balloon tonometer catheter surgically placed in the submucosal space. Hemodynamic and arterial blood gas parameters were unchanged at flow mode conversion. Although oxygen delivery was comparable between pulsatile and non pulsatile circulation, oxygen extraction ratio was lower and venous oxygen saturation was higher in non pulsatile than pulsatile circulation. Although statistically not significant, serum lactate level tended to be higher with non pulsatile circulation. No difference was observed in esophageal mucosal blood flow between pulsatile and non pulsatile circulation, whereas intramucosal pH, which strongly correlated with arterial pH regardless of the flow mode, was significantly lower under non pulsatile than pulsatile conditions. In conclusion, systemic oxygen uptake is less efficient in non pulsatile than pulsatile circulation in the setting of an acute experiment using animals, which may be accounted for by the disparity between the pre capillary blood flow and actual tissue oxygen metabolism.

Animals↗

Importance of metabolic function of the natural lung evaluated by prolonged exclusion of the pulmonary circulation.

It is generally considered that the natural lung metabolizes various vasoactive substances through the pulmonary circulation. However, the influences of bypassing or eliminating the pulmonary circulation have not been fully elucidated, especially for prolonged periods. In this study, we performed total cardiopulmonary bypass and exclusion of the pulmonary circulation for up to 336 hr in awake goats to clarify the importance of the metabolic function of the lung. In seven adult goats, biventricular bypass with a pulsatile ventricular assist system was first established. After 2 weeks, the biventricular bypass was converted to total cardiopulmonary bypass without anesthesia. Adequate gas exchange and perfusion support were achieved in all animals. However, the institution of total cardiopulmonary bypass led to marked decreases in the mean aortic pressure and systemic vascular resistance, and they remained low thereafter. The arterial levels of prostaglandin E2 and norepinephrine, which are inactivated naturally through the pulmonary circulation, increased remarkably. These results indicate that the natural lung plays an important role in controlling systemic circulation by metabolizing various vasoactive substances. Understanding the non respiratory function of the natural lung is of prime importance for advancement of lung and heart-lung support.

Animals↗

Development of an integrated artificial heart-lung device for long-term cardiopulmonary support.

An integrated artificial heart-lung device has been developed as a long-term cardiopulmonary support system. The device is composed of gas exchange and pumping units. The gas exchange unit consists of a special hollow fiber membrane that can prevent serum leakage. The entire blood contacting surface of the gas exchange unit is treated with covalent heparin bonding. The pumping unit consists of two pusher-plate artificial hearts joined to each end of the artificial lung unit. The core size and priming volume of the device are 11 x 14 x 17 cm and 400 ml, respectively. In in vitro evaluation, the device exhibited a maximum output of 7.0 L/ min, with a pressure gradient of 10 mmHg per 1 L/min flow rate. In acute in vivo evaluation with adult goats, the device satisfactorily replaced the animals' circulation and respiration for 6 hr. Pumping output ranged from 5.5 to 6.0 L/min, whereas PaO2 and PaCO2 were kept above 500 mmHg and below 30 mmHg, respectively. The device demonstrated prominent thrombus resistant properties in nonheparin animal use trials. These results indicate that the integrated artificial heart-lung device has a potential to be a long-term cardiopulmonary support system that can be used with minimal anticoagulant therapy.

Animals↗

Development of a membrane oxygenator for long-term respiratory support and its experimental evaluation in prolonged ECMO.

The authors developed a new membrane oxygenator (MO) for long-term respiratory support and evaluated its performance in animal experiments for as long as 336 hr. The MO, with a membrane area of 1.2 m2 and priming volume of 140 ml, is compact and designed to be interposed in a ventricular assist system (VAS) conduit. It is made with a novel hollow fiber membrane, in which micropores are blind-ended so that serum leakage can be prevented during prolonged use. The blood contacting surface of the MO is heparinized with a newly developed covalent bonding technique that ensures good thrombus resistance. In vivo evaluation with five adult goats was performed by installing the MO into a venoarterial or venovenous bypass circuit. No systemic anticoagulant therapy was used, except for a heparin-added fluid infusion to keep the pressure monitoring lines open (2-3 U/kg/hr). Throughout the experiments, no plasma leakage was observed, and gas transfer rates were maintained in a satisfactory range. Platelet counts did not decrease to less than 60% of levels before bypass, and hemolysis was negligible. The levels of coagulation parameters including fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), antiplasmin, prothrombin time (PT) and activated partial thromboplastic time (APTT) remained within physiologic ranges and relatively constant. At the end of the evaluation, no thrombus formation was noted in three of five MOs. These results suggest that this MO is a promising device for long-term respiratory support.

Animals↗

Altered oxygen metabolic conditions associated with increased norepinephrine levels in a nonpulsatile systemic circulation.

Change in oxygen metabolic conditions accompanying the conversion of systemic flow from pulsatile to nonpulsatile (from P-mode to N-mode) was investigated in association with blood norepinephrine levels. Total left heart bypass was instituted through a left thoracotomy under general anesthesia in 10 adult goats. Pulsatile and nonpulsatile pumps were incorporated in the circuit in parallel, and the flow character was rapidly converted from the P-mode to the N-mode. Norepinephrine levels increased significantly after the conversion, from 222 +/- 54 pg/ml to 285 +/- 65 pg/ml. While oxygen delivery (DO2) was kept constant, the oxygen extraction ratio significantly decreased, from 21 +/- 3% to 16 +/- 3%, and venous oxygen saturation (SvO2) significantly increased, from 77 +/- 6% to 84 +/- 6% after depulsation. The serum lactate level was significantly higher in the N-mode than the P-mode (P-mode: 35 +/- 2 mg/dl, N-mode: 45 +/- 5 mg/dl). Strong positive and negative correlations of norepinephrine levels were observed with oxygen extraction ratio and SvO2, respectively, whereas norepinephrine levels did not correlated with DO2. Regression lines in these correlations unveiled higher oxygen uptake in the P-mode than the N-mode at the same norepinephrine level. These results indicate that, in the setting of an acute animal experiment, oxygen uptake is less efficient with the absence of pulsatility, and the higher norepinephrine concentration functioned to tune the oxygen metabolism in the initial stage of nonpulsatile systemic circulation.

Animals↗

Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy.

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.

Adolescent↗

Characterization and optimization of the flow pattern inside a diaphragm blood pump based on flow visualization techniques.

We applied two different flow visualization techniques to obtain detailed information on the inside flow of the diaphragm blood pump of our electrohydraulic total artificial heart system to determine the optimum washout effect that would result in better antithrombogenicity. Major orifice directions of the inflow and outflow Bjork-Shiley valves of the left blood pump were independently changed to create 17 varied patterns. The character and velocity of the main flow at the diaphragm-housing junction were acquired using a laser light sheet method with polyethylene tracers. Wall shear flow, a major factor governing washout in the blood pump, was estimated by a newly developed paint erosion method. In this method, quantitative evaluation for an index of washout effect was made by calculating the residual ratio of the paint on the blood pump inner surface at 30 sec of pumping. When a single circular flow was consistently observed by the laser light sheet method, the paint residual ratio become low, indicating washout was relatively good. At the lowest paint residual ratio, the center of the circular flow observed by the laser light sheet method was located at the geometric center of the blood chamber. In conclusion, the flow pattern inside the blood pump could be characterized by combined use of these two flow visualization techniques, and the significant role of circular flow in better washout was clarified.

Heart, Artificial↗

Transcutaneous optical telemetry system with infrared laser diode.

A transcutaneous telemetry system is indispensable when monitoring and controlling the operation of an artificial heart totally implanted inside the body. A telemetry system using light is more useful than radio waves from the viewpoint of electromagnetic interference and power consumption. In this report, a transcutaneous optical coupler consisting of an infrared laser diode (LD) and a PIN photodiode (PINPD) was evaluated, and the transcutaneous optical coupling and information transmission characteristics were evaluated in in vitro experiments. The wavelength and directional angle of the LD used were 830 nm and 9.5 degrees, respectively. With regard to the directional angle of PINPD, the authors found that a PINPD with a larger directional angle allowed for more deviation between the axes optical axes of the LD and the PINPD. It was also found that the transcutaneous coupler had an optimum distance for the permissible deviation to be maximized. The information signals modulated by the phase shift keying (PSK) were transmitted at a rate of 9,600 bps through goat skin 4 mm thick, and demodulated by the phase locked loop (PLL) on the receiving side. As a result, the information signals were demodulated without any errors in deviation within 10.5 mm at a distance of 11 mm. In conclusion, the transcutaneous optical telemetry system using an infrared LD has sufficient characteristics to monitor and control the operation of an artificial heart totally implanted inside the body.

Heart, Artificial↗

Hemodynamic effects of prostaglandins and catecholamines in graded reduction of pulmonary flow during venoarterial bypass in awake goats.

The roles of prostaglandins and catecholamines in the hypotensive hemodynamic change during cardiopulmonary support with a venoarterial bypass (VAB) were investigated in a series of chronic animal experiments of gradually reduced pulmonary arterial blood flow (PAF). The VAB system consisted of a pulsatile ventricular assist device, an artificial lung, and the right atrium uptake and descending aorta return cannulae in four adult goats weighing 49-51 kg. The PAF was adjusted to 50, 10, and 0% of the total systemic blood flow. Indomethacin, an inhibitor of prostaglandin production; phentolamine, an alpha-antagonist of catecholamine; and noradrenaline, an agonist of catecholamine were administered at each PAF condition. The mean aortic pressure (mAoP) and the systemic vascular resistance decreased in proportion to the decrease in PAF. Indomethacin increased the mAoP at all PAF conditions, indicating a relationship between prostaglandins and hypotension. Phentolamine decreased the mAoP at all PAF conditions, indicating a normal response of catecholamine receptors. However, noradrenaline increased the mAoP at 50 and 10% PAF, but did not appreciably increase the value at 0% PAF, indicating complete response of catecholamine receptors to endogenous catecholamines at 0% PAF only. In conclusion, prostaglandins play a substantial role in hypotension during VAB, and catecholamines may subsequently increase in compensation for extreme hypotension.

Adrenergic alpha-Agonists↗

Selection of a rechargeable internal back-up battery for a totally implantable artificial heart.

Three kinds of rechargeable batteries, NiCd, NiMH, and Li+, were compared for the purpose of selecting the most appropriate battery for use in a Rechargeable Internal Back-up Battery (RIBB) unit for a Totally Implantable Artificial Heart. Batteries of each kind were connected in series to obtain the required driving voltage of 24 V. The NiCd and NiMH batteries were charged by a constant current of 1 C, and the Li+ batteries were charged first by a constant current of 1 C and later by a constant voltage of 28.7 V. All three types of batteries were discharged using a dummy electronic pulsatile load consuming 20 W of power. The tests showed that the Li+ batteries were capable of supplying the required energy for more than 60 minutes. The Li+ batteries had a specific energy of 121.5 Wh/kg, which was more than 3x that of the NiCd and NiMH, and an energy density of 282.5 Wh/L more than double that of the other two. In addition, the Li+ batteries recorded the least temperature rise during charging and discharging. The results of our tests conclusively showed that the Li+ battery is the best among the three for use in an RIBB from the viewpoint of energy density and temperature rise.

Electricity↗

Effects of long-term nonpulsatile left heart bypass on the mechanical properties of the aortic wall.

We investigated the mechanical properties of the descending aortic wall relative to its structural change caused by reduced pulse pressure in long-term nonpulsatile left heart bypass (LHB). Fifteen adult goats (53-68 kg) were divided into three groups: five goats underwent LHB with a nonpulsatile pump for 31 to 381 days (Group N), five goats underwent LHB with a pulsatile pump for 24 to 130 days (Group P), and the other five goats were used as normal control animals (Group C). The aortic pulse wave pressure was 17+/-7 mm Hg in Group N, 43+/-1 mm Hg in Group P, and 39+/-2 mm Hg in Group C. Structural changes were evaluated using wall thickness and the volume ratio of elastin and collagen. The mechanical properties were evaluated using "beta," which was calculated according to the equation: = (In P/Ps)/(Do/Ds-1), where Ps was the standard pressure, Ds was the wall diameter at pressure Ps, and Do was the wall diameter at pressure P. The wall thickness of the aortic wall in Group N (1.6+/-0.3 mm) was significantly thinner than that in either Group P (2.2+/-0.3 mm) or Group C (2.1+/-0.2 mm). The volume ratio of elastin in Group N (51 +/- 3%) was higher than that in Group P (44+/-1%) or Group C (40+/-1%), whereas no significant difference was found in the volume ratio of collagen between those in Group N (10+/-1%), Group P (9+/-2%), and Group C (10+/-1%). The stiffness parameter, beta, in Group N (3.1+/-0.7) was slightly higher than that seen in Group P (2.9+/-0.4) or Group C (2.9+/-0.2), but there was no significant difference between the three groups. These results indicate that long-term nonpulsatile LHB caused marked structural changes in the aortic wall, whereas the change in mechanical properties were not significant with regard to stiffness.

Animals↗

Control of a total artificial heart using mixed venous oxygen saturation.

We developed a control of the total artificial heart (TAH) using mixed venous oxygen saturation (SvO2). With this method, the TAH output was controlled by automatically adjusting drive parameters in response to changes in measured SvO2. The feasibility and validity of this method were evaluated in a series of treadmill exercise tests using a calf implanted with a pneumatic TAH. The cardiac output (CO) and SvO2 were measured with an ultrasonic flowmeter and an oximetric catheter, respectively. The calf performed graded exercise under a fixed drive control mode (fixed mode), in which the drive parameters were unchanged throughout the treadmill test, and under the SvO2 based control mode (SvO2 mode). The calf could go to Stage 6 in both modes, but the maximal oxygen consumption in the SvO2 mode was 1.5 times as large as that of the fixed mode. Compared with the fixed mode, CO was increased effectively in the SvO2 mode, and the capacity for exercise was augmented. When considering the relationship between oxygen consumption and oxygen delivery, it was revealed that the CO in the SvO2 mode responded more adequately to the recipient's oxygen demand than that in the fixed mode. We conclude that this SvO2 based control method is feasible and physiologically effective.

Animals↗

A transcutaneous energy transmission system with rechargeable internal back-up battery for a totally implantable total artificial heart.

We have been developing an externally coupled transcutaneous energy transmission system (ECTETS) for a totally implantable total artificial heart (TITAH). When the ECTETS is unable to supply the energy to drive the TITAH from outside the body, a rechargeable internal back-up battery (RIBB) implanted inside the body is used as a back-up to supply the required energy. This paper reports on the performance characteristics of our ECTETS with an RIBB. In this study, a lithium-ion (Li+) secondary battery was used as the RIBB. The transcutaneous energy transmission and the charging control characteristics of the ECTETS, while simultaneously supplying energy to the TITAH and the RIBB, were evaluated in an in vitro experiment. The output power and transmission efficiency of the ECTETS operating in this mode were found to vary from 20 W to 34 W and from 84% to 71%, respectively. It was also found that a sufficient power of more than 20 W could be supplied to the TITAH. The time needed to fully charge the RIBB was 117 minutes, and a fully charged RIBB could drive the TITAH, consuming 20 W for 62 minutes. It may, therefore, reasonably be concluded that the ECTETS with the RIBB is sufficient to drive the TITAH.

Animals↗