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Biomedical subjects

Y Wakisaka

Publications and source records attributed to Y Wakisaka.

At least 73 records · Page 4Linked to original sources

Acute phase responses of vasoactive hormones to non pulsatile systemic circulation.

Acute phase responses of vasoactive hormones to the rapid conversion of a systemic flow pattern from pulsatile or non pulsatile mode to the reverse were assessed in 20 goats weighing 45-69 kg. A total left heart bypass was instituted under general anesthesia, with pulsatile and non pulsatile pumps interposed in the circuit in parallel, and the systemic flow mode was rapidly and bidirectionally converted from the pulsatile mode or non pulsatile mode to the reverse. Vasoactive hormone levels and hemodynamics were evaluated before and after 5 min of conversion. No significant difference was observed between the modes either in blood flow or systemic vascular resistance, while the mean aortic pressure was significantly higher in the non pulsatile mode than the pulsatile mode (106.7 +/- 2.4 versus 99.9 +/- 3.5 mmHg). Among various vasoactive hormone levels evaluated, only norepinephrine showed a significant difference between the modes, where concentration in the non pulsatile mode was significantly higher than the pulsatile mode (391.0 +/- 60.7 versus 309.4 +/- 42.5 pg/ml). No correlation was found between the absolute values of mean aortic pressure and norepinephrine level, whereas a significant reciprocal correlation was detected between the magnitude of inter-mode differences in these two parameters. In conclusion, a non pulsatile systemic circulation does not exert significant influence on vasoactive hormone levels, except for slight increase in norepinephrine with a reciprocally correlated increase in mean aortic pressure. It is deduced that activity of the sympathetic nervous system represented by norepinephrine level is higher in the non pulsatile mode than the pulsatile mode, and the baroreceptor reflex functions in an acute phase after flow mode conversion.

Acute-Phase Reaction↗

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 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↗

Power of the fatigue resistant in situ latissimus dorsi muscle.

To evaluate the in situ latissimus dorsi muscle as an actuator for circulatory assistance, 1) muscle power was analyzed in animal experiments, and 2) muscle weight was measured in human cadavers. Three adult goats underwent 12 week preconditioning. The insertion of the latissimus dorsi muscle was then connected to a spring and a tension transducer in series. The stroke length was measured with a photosensor without power loss. With contraction of muscles under various loads, tension-length relationships at end contraction and end relaxation were obtained and the maximum area of a square drawn within both lines was assumed to be maximum external power. Good fatigue resistance and the highest maximum external power of 3.16 Watts/kg at 120 min was derived from preconditioned latissimus dorsi muscle in burst frequency of 50 Hz. Muscle weight in 42 human cadavers was negatively correlated with age (r = 0.56) and was expected to be 221.6 g in patients aged 45 years. According to these data, the power of a human preconditioned latissimus dorsi muscle was estimated as 0.7 Watts. It was concluded the power of in situ preconditioned latissimus dorsi muscles was appropriate for right heart assistance or counterpulsation for left heart assist.

Aged↗

An approach to reducing hemolysis in an axial-flow blood pump.

In an attempt to decrease hemolysis caused by an axial-flow blood pump, we studied whether specific speed (Ns) at a design point (determined by flow in m3/min, pump head in m, and pump speeds in rpm), should be kept within the existing engineering standard range (1000 < Ns < 2500) or whether pump speed should be reduced to a minimum (Ns < 1000). Four pumps (A: 14,000 rpm, B: 18,000 rpm, C: 22,000 rpm, and D: 26,000 rpm), each with an impeller 11.8 mm in diameter, were designed to accommodate a flow rate of 5 L/min and a pressure head of 100 mmHg. At this design point, the Ns of each pump was calculated as A:758, B:974, C:1191, and D:1407. Pump performance was observed, and the total efficiency of each pump was calculated. The hemolysis index (HI) was calculated after simultaneous testing in duplicate of all four pumps using fresh goat blood (anticoagulated with citrate-dextrose solution) in a closed mock-loop circuit. Total efficiency of each pump was calculated as A:49%, B:50%, C:45%, and D:22%. In the first hemolytic test, HIs were measured as A:0.066, B:0.18, and C:0.13; a water seal failed in pump D. In the second test, HIs were B:0.077, C:0.0499, and D:0.12; a bearing failed in pump A. It is concluded that a lower level of hemolysis is associated with a pump speed in the minimum range at the design point, even though Ns is outside the standard range.

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↗

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↗

A two stage axial flow pump. New approach to reduction of hemolysis.

From an engineering point of view, the suitable revolution number for high efficiency operation of an axial flow pump is known. A multistage axial flow pump is a useful tool for reducing revolution number with a high efficiency axial flow pump. A two stage (25) axial flow pump designed at a 5 L/min flow rate and a 100 mmHg pressure head was evaluated in three kinds of in vitro hemolysis tests. Each stage design point of the 2s pump was tested at a 5 L/min flow rate and a 50 mmHg pressure head. Specific speed and revolution number of the 2S pump were 1400 rpm, m3/min, m, and 15500 rpm, respectively. In the first test the 2S pump was compared with two single stage axial flow pumps (1S-A and 1S-B100) designed by the same method. The specific speed of the 1A was the same as that of the 2S pump, which was driven at 26000 rpm. The impeller of the 1S-B100 was the same as that of the 2S pump, which was driven at a 22000 rpm RN and a 1100 specific speed. The 2S pump was separated into two single stage axial flow pumps and the effect of series operation on hemolysis was evaluated in the second test. In the third test the 2S pump was compared with the 1S-B100 by using diluted goat blood samples with three different hematocrit values. The results showed that the hemolysis index of the 2S pump, regarded as a total hemolysis index of both stage axial flow pumps, was less than those of the single stage axial flow pumps at all hematocrit values.

Animals↗

Hemodynamic and humoral conditions in stepwise reduction of pulmonary blood flow during venoarterial bypass in awake goats.

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 +/- 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50, 25, 10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 +/- 14 to 66 +/- 3 mmHg and from 1,288 +/- 77 to 740 +/- 73 dyne.sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 concentration increased from 1.5 +/- 0.6 to 8.8 +/- 0.6 pg/ml following the decrease in PAF from 100 to 0%. The renin-angiotensin system increased in proportion to the decrease in PAF. In contrast, the epinephrine and norepinephrine concentrations (60 +/- 10 and 227 +/- 80 pg/ml, respectively, at 100% PAF) did not change appreciably even at 10% PAF, but were markedly elevated to 335 +/- 117 and 2,088 +/- 1,503 pg/ml at 0% PAF. The antidiuretic hormone level similarly changed. In conclusion, decrease in PAF during VAB exerts significant effects on hemodynamics in a proportional manner and on vasoactive humoral factors in a diverse manner.

Animals↗

In vitro and in vivo heat dissipation of an electrohydraulic totally implantable artificial heart.

The authors evaluated the heat transfer characteristics of an electrohydraulic totally implantable artificial heart (EH-TAH) developed at our institute. In three in vitro experiments, the heat dissipation of the EH-TAH was investigated. First, the EH-TAH was connected to a closed mock circuit filled with 1 L of saline, and driven at an input power of 20 W. The estimated heat conducted to the blood was approximately 10.3 W, which was almost half of the input power. Second, we simulated heat transfer with the circulation of a calf by using a heat exchanger. The amount of heat dissipating directly from the EH-TAH surface was calculated to be 10 W. Third, the temperature of the actuator examined with thermography was found to be almost uniform, and no prominent high temperature area was observed. In an in vivo study, the EH-TAH was implanted for 10 days in a calf weighing 62 kg. The input power was 18 +/- 2 W, the temperature of the actuator-tissue contacting surface was 39.4 +/- 0.8 degrees C, and that of the pump blood chamber was 39.8 +/- 0.4 degrees C. This slight temperature elevation was thought to be attributable to heat dissipation to the blood. On histologic study of the chest wall and the lung in contact with the actuator, vascularized connective tissue envelopes were observed, but unfavorable side effects, such as tissue necrosis, were not observed. These results suggest that the thermal effect of this system is acceptable at the input power used.

Animals↗

Development of an implantable centrifugal blood pump for circulatory assist.

An implantable centrifugal pump (ICP) for prolonged circulatory assist has been developed, at 320 ml and 830 g. A central balancing hole was made in its impeller for better antithrombogenicity. Waterproofing and histocompatibility were supported by a silicone seal and a casing made of titanium and acrylic resin. Overall efficiency was 30% and normalized index of homolysis was 0.003 mg/dl, the same value as the BP-80, at a flow rate of 5 L/min and a head of 100 mmHg. Antithrombogenicity and hemolytic properties of the ICP were investigated in paracorporeal implantation in three goats (61-71 kg). Exothermicity, anatomic fit, and water tightness of the ICP were evaluated in intrathoracic implantation in an adult goat (66 kg). The ICP could run paracorporeally for 50, 200, and 381 days. There was no thrombus in the ICP after 381 days' pumping, and the ICP could run in the chest cavity for 40 days. The temperature of the motor rose 1.8 +/- 0.3 degrees C from that of the pleura. Moisture content of the seal remained normal. The ICP was completely covered with smooth fibrous tissue. Although a small area of atelectasis was found in the lingula, neither lung adhesion nor necrosis of the chest wall was observed. The ICP has satisfactory antithrombogenicity, hemolytic property, water tightness, anatomic fit, and exothermicity for use as an implantable circulatory assist device.

Animals↗

Establishment of flow estimation for an implantable centrifugal blood pump.

A less invasive and non thrombogenic flow estimation of an implantable centrifugal blood pump (ICBP) has been developed, which was derived from electric power consumption, the rotating speed of a motor, and blood viscosity presumed by hematocrit and body temperature. The power consumption and the rotating speed of the motor were measured by a wattmeter every 0.2 sec. Accuracy and stability of the estimated flow (EF) were investigated during in vitro and in vivo experiments. The EF was compared with a measured flow rate (MF) monitored by an electromagnetic flowmeter. During in vitro experiments, the EF and MF were measured at 79 operating points. The ICBP was driven in a closed mock loop filled with goat blood with hematocrit values of 21.5, 28, 34, and 42%. During in vivo experiments, the ICBP was implanted in the chest cavity of a goat and driven for 40 days with continuous estimation of the bypass flow rate. Blood was taken to determine hematocrit value several times a week. The temperature of the pleura away from the ICBP was measured every 15 min. A linear correlation between the EF and MF was observed, and the correlation coefficient between the EF and MF was 0.99 during in vitro examinations. An averaged error of the EF was 0.5 L/min, with the MF ranging from 2.3 to 8.1 L/min during in vivo experiments. In conclusion, flow estimation was established with good stability and accuracy in both in vitro and in vivo experiments.

Animals↗

Early changes in circulating blood volume and volume regulating humoral factors after implantation of an electrohydraulic total artificial heart.

The early changes in circulating blood volume (CBV) and volume regulating humoral factors after implantation of an electrohydraulic total artificial heart (EH-TAH) were investigated in a calf and compared with results in a sham operated control calf. CBV was measured by the dye dilution method using indocyanine green. CBV and humoral factors were periodically investigated. In the EH-TAH implanted calf, the cardiac output was estimated at 6-7 L/ min (94-109 ml/kg/min), and the aortic pressure and aerobic metabolic condition were favorable. Nevertheless, the CBV was increased to 132 and 168% of the pre-operative value (range in the control calf, 83-103%) on post operative days 4 and 8, respectively. The atrial natriuretic peptide level on days 2, 5, and 7 was 23, 170, and 240 (in the control calf, 19-61) pg/ml, respectively, and the antidiuretic hormone level was 7.3, 2.0, and 1.3 (0.5-1.3) pg/ ml, respectively. The plasma renin activity was 3.2, 3.7, and 3.1 (0.5-0.3) ng/ml/hr, respectively. The angiotensin-I and angiotensin-II levels were also increased in the EH-TAH implanted calf. It is concluded that significant water retention occurs even at sufficient cardiac output early after EH-TAH implantation. The changes in humoral factors are suggested to arise secondary to the increased CBV or other unknown factors.

Angiotensin I↗

Characteristics of mixed venous oxygen saturation and physical activity as parameters for artificial heart control.

Mixed venous oxygen saturation (SvO2) and physical activity (PhyAc) are practical candidates as parameters of total artificial heart (TAH) control because SvO2 can be measured through a transparent blood pump housing with infrared rays and PhyAc can be calculated from signals of an accelerometer used for rate response pacemakers. Although the methods for measurement of the parameters have already been developed, characteristics of these parameters for TAH control, such as during exercise, are still unclear and were examined in this study. SvO2, cardiac output (CO), and PhyAc were measured as parameters. Multi-stage treadmill exercise tests were performed. Difference values (DVs) from the value at the start of exercise showed better correlation than did absolute values. Correlation coefficients between DV in CO and DV in SvO2 and between DV in CO and PhyAc were high at -0.82 and 0.72, while the time constants for the change of SvO2 and CO to the PhyAc change were 26 and 32 sec. Although the correlation coefficient between the CO and SvO2 was higher than that between CO and PhyAc, PhyAc responded more quickly to the speed change compared with the response of SvO2 and CO. It was concluded that SvO2 and PhyAc were useful parameters with different characteristics for TAH control during exercise.

Animals↗