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Biomedical subjects

H Akagi

Publications and source records attributed to H Akagi.

At least 199 records · Page 11Linked to original sources

In vitro and in vivo assessment of an intravenous axial flow pump for right heart assist.

Right ventricular (RV) function is a limiting factor in maintaining systemic circulation with circulatory assist. There is, however, no easy way to institute RV assist, such as the intraarterial axial flow pump (Hemopump) used for left heart assist. In this study, the feasibility and hemodynamic effect of intravenous use of an axial flow pump was examined. A pump system was developed with an outflow cannula and an impeller that were newly designed for intravenous insertion with a Hemopump driving system. The pump system characteristics using goat blood at a hematocrit of 26% indicated that maximum flow at a pressure differential against 40 mmHg is 3.2 l/min at a pump speed of 28,000 rpm. The pump was tested in adult goats by intravenous insertion through a 14 mm, low porosity graft anastomosed to the infrarenal inferior vena cava. The pump was advanced until the tip of the cannula was positioned at the main pulmonary artery, using balloon catheter guidance under fluoroscopy. RV assistance was evaluated by pressure tracing, and aortic flow (AF) measured by electromagnetic flowmeter under 1) induced pulmonary stenosis (PS), and 2) electrically induced ventricular fibrillation (VF) in combination with left heart assist. Under PS, right atrial pressure decreased from 11 to 2 mmHg and AF increased from 1.0 to 4.1 l/min after initiation of the pump. Under VF, AF and aortic pressure were 2.6 l/min and 78 mmHg, respectively, with left ventricular assist. After initiation of the pump, they increased to 4.0 l/min and 98 mmHg, respectively. In chronic experiments using three adults goats for up to 48 hr, levels of plasma hemoglobin and platelet counts were maintained within an acceptable range. There was no prominent damage to the hearts. These data suggest that an axial flow pump introduced by an intravenous approach without thoracotomy is feasible and provides sufficient right heart assist.

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↗

Improvement of water-soluble cephalosporin derivatives having antibacterial activity against methicillin-resistant Staphylococcus aureus.

We evaluated a series of novel cephem antibiotics, N-alkylpyridinium (alkyl group), N-carboxyethylpyridinium (carboxylic group), N-sulfoethylpyridinium (sulfonic group) and N-alkylquaternary ammonium salts (ammonioethyl group), N-alkyl-aromatic-quaternary ammonium salts and N-alkyl-heterocyclic quaternary ammonium salts (cyclic group) as vinylthio pyridinium derivatives at the C-3 position and hydroxyiminoaminothiazol at the C-7 position, for their activity against methicillin-resistant Staphylococcus aureus (MRSA) and their solubility, by measuring the minimum inhibitory concentrations (MICs) and the dissolving test in phosphate buffer. All tested compounds, except for the alkyl group, showed good solubility (>10%) in 1/15 M phosphate buffer (pH 7.2). The concentrations required to inhibit 80% of the bacterial strains (MIC80s) of the alkyl group, carboxylic group, sulfonic group, ammonioethyl group and cyclic group against MRSA were 1.56, 12.5-25, 6.25, 1.56 and 1.56 microg/ml, respectively. These results indicated that the ammonioethyl and cyclic groups yield the maximum anti-MRSA and anti-Enterococcus faecalis activity, and also good water solubility.

Cephalosporins↗

Laryngeal zoster with unilateral laryngeal paralysis.

The case of a 60-year-old man with a unilateral laryngeal mucosal lesion and complete left vocal cord paralysis is reported. The lesion localized to the left side of the larynx covered the laryngeal vestibule, arytenoid, false vocal cord and true vocal cord, but did not extend to the hypopharynx or oropharynx. Enzyme immunoassay for varicella-zoster virus (VZV) led to a diagnosis of VZV infection.

Antibodies, Viral↗

Differential diagnosis between organic and inorganic mercury poisoning in human cases--the pathologic point of view.

Differences in pathology were found between acute and chronic exposure to methylmercury, mercury vapor, and inorganic mercury. Characteristic pathologic changes produced by organic mercury in the brain have previously been described in patients with Minamata disease. The brains of patients who presented with acute onset of symptoms and died within 2-mo showed loss of neurons with reactive proliferation of glial cells, microcavitation, vascular congestion, petechial hemorrhage, and edema in the cerebral cortices, predominantly in the calcarine, pre- and postcentral, and transverse temporal cortices and in the cerebellar cortex. The neuropathologic changes in the patients with acute onset of symptoms who survived for a long period (>10 yr) were also included neuronal loss with reactive proliferation of glial cells in similar anatomic locations. The neuropathologic changes in patients with inorganic mercury poisoning are quite different. Autopsies performed on 3 individuals with fatal cases of acute inorganic mercury poisoning who were exposed to mercury vapor for about 2 wk revealed diffuse organized pneumonia, renal cortical necrosis, disseminated intravascular coagulopathy, and infarctions in the brain and kidneys. In 2 other patients who worked in mercury mines for about 10 yr and who suffered from chronic inorganic poisoning, no specific lesions were demonstrated in the brain. However, the assay and the histochemistry of mercury revealed that inorganic mercury was present in the brain in all 3 groups irrespective of the brain lesions and the duration of clinical signs.

Adult↗

Cyclosporin A and its metabolites, distribution in blood and tissues.

Cyclosporin A (CsA), a non-myelotoxic immunosuppressant, and its metabolites are widely distributed in the body. Highest concentrations of CsA have been detected in the pancreas, adipose tissue and liver, lowest concentrations in brain, muscle, blood and other body fluids. Metabolites are distributed differently to CsA. In addition to lipid partition, intracellular binding to cyclophilin, a peptidyl-prolyl cis-trans isomerase, appears to play a role in its tissue distribution. The temperature dependence of such binding in erythrocytes poses difficulty in serum or plasma measurements. Tissue specific processes may also influence action and toxicity of CsA and its metabolites; thus, a better understanding of the complex distribution pattern of CsA and its metabolites would be important for establishing improved strategies and selection of appropriate specific methodologies for drug monitoring.

Animals↗

Chronic evaluation of a compact nonseal magnet pump as a nonpulsatile pump for long-term use.

Use of a nonpulsatile pump is one of the most interesting approaches in the development of artificial hearts. A centrifugal pump without a seal around the rotating part was evaluated in five goats. The size of the pump is 8.4 cm x phi 7.0 cm, including an electric motor. A polypropylene impeller with four fins on the top of a column in which a magnetic ring is embedded spins by coupling with a rotating magnet outside the housing. In the goats, the pump was placed paracorporeally to provide total left heart bypass at a flow rate of 4.6-7.6 L/min, and activated clotting time was controlled at 200-300 sec by continuous heparin infusion. Although the first three goats died within 3 days due to bleeding, embolism, and a jammed impeller, respectively, a pump could be driven for 14 days in the fourth goat, and another pump with a rotational control feedback system ran for 32 days in the fifth goat. Plasma free hemoglobin levels were 13.8 +/- 4.3 mg/dl and 9.5 +/- 2.5 mg/dl, and platelet counts were 53.8 +/- 24.7 x 10(4)/mm3 and 62.0 +/- 22.0 x 10(4)/mm3 after 12 hours and 7 days pumping, respectively. No thrombus was observed in the blood chamber in the last two cases. In conclusion, this pump has possibilities as a nonpulsatile pump for long-term use.

Animals↗

Easy access for a left ventricular assist system without thoracotomy.

In a previous article, a left ventricular assist system (LVAS) with a percutaneous transseptal cannulation technique for easy application was described. This system was safe and efficient (maximum output greater than 3 L/min) and fitted between the intraaortic balloon pumping and LVAS with thoracotomy. But technical skill for placement was slightly complicated. The cannulation system has been improved. In the new system, the inlet cannula is initially used as a sheath introducer and is quickly inserted into the left atrium after transseptal puncture. The new inlet cannula is made of polyvinyl chloride (TM100, Toyobo, Co., Ltd., Osaka, Japan), which has excellent antithrombogenicity and low friction using a polyester plasticizer. The distal part is designed to be flexible with a spiral wire for easy manipulation. A sealing hub was installed to prevent bleeding at the proximal The simplicity and safety of the new system were examined in chronic animal experiments. The inlet cannula was placed into the left atrium within a few seconds after transseptal puncture. During 20 days of activation, there were no episodes of systemic or pulmonary embolism, although no anticoagulant was used. Under fluoroscopy, there was no thrombus formation around the cannula at removal. On the 14th day after removal, the puncture site of the septum had healed. This system is ready for clinical use and shows promise of satisfactory safety and manageability.

Animals↗

An integrated artificial heart-lung device.

An integrated artificial heart-lung device (IAHLD) is being developed as a novel system for simultaneous long-term support of heart and lung. The IAHLD consists of an artificial lung component (LC) and two blood pumps. The LC is made with a special composite hollow fiber membrane that prevents serum leakage. The fibers are arranged as piled-up lattices and potted in a cylindrical housing made of polyurethane. The blood pump with a single port is of a pneumatic pusher-plate type, and a Björk-Shiley valve is mounted in the port. The LC is sandwiched between the inlet and outlet pumps, and all components are integrated. This special structure provides high gas exchange efficiency, prevention of flow channeling and stagnation, and reduction of blood contacting surfaces. The prototype IAHLD had exchange rates of up to 170 ml/min of O2 and CO2 and up to 5.5 L/min of pump output. A flow visualization analysis with cineroentgenography revealed that the flow distribution within the IAHLD was uniform, without any stasis. It was concluded that the IAHLD is a promising system for long-term heart and lung support, and can be used without systemic heparinization given thromboresistant surface treatment as the next step of development.

Animals↗

Serum silicon levels in recipients of an electrohydraulic ventricular assist system.

This study was designed to determine the permeation rate of silicon oil from the authors' electrohydraulic ventricular assist system (EHVAS), and to evaluate influences on organ function. The permeation rate through the diaphragm of the EHVAS was determined by in vitro experiments. Influences on organ function were evaluated in three goats with EHVAS by monitoring blood chemical parameters and serum silicon levels (S-Si). The permeation rate from the EHVAS was about 0.2 ml/month, calculated from the data obtained in the in vitro experiments. S-Si levels did not increase during chronic animal implantation, and renal and hepatic function were not affected. The permeation rate through the diaphragm must, however, be taken into consideration.

Animals↗

Peripheral circulation during nonpulsatile systemic perfusion in chronic awake animals.

Peripheral circulation (PC) during nonpulsatile (NP) perfusion is not satisfactorily understood, although it is known that animals can survive with chronic NP flow. In awake goats, PC was analyzed by hemodynamic and hormonal parameters, tissue blood flow of the ear measured by a noninvasive laser Doppler flowmeter, and distribution of the body surface temperature monitored by thermography. An NP systemic circulation was established in five 40-64 kg goats with a centrifugal pump (MD-10, Iwaki Pump, Japan) that replaced a pulsatile ventricular assist device 2 weeks postoperatively; this was done without anesthesia. Nonpulsatile total left heart bypass was obtained, with flow rates of 78-165 ml/kg/min. Systemic vascular resistance and blood adrenalin and noradrenalin levels were not affected by the depulsation. Tissue blood flow during NP perfusion was well maintained and showed comparable values to those during pulsatile systemic circulation. Vasomotion of 10-20 cycles/min was obvious in the tissue blood flow pattern, indicating adequate PC at each sampling point. Thermography before and after depulsation indicated no change of temperature distribution, and displayed warm peripheral areas. In conclusion, PC of animals on chronic NP systemic perfusion is adequately maintained.

Animals↗

Hybrid respiratory support system with extracorporeal placental oxygenation.

The authors developed a novel hybrid system for long-term respiratory support with extracorporeal placental oxygenation. In this system, the patient's blood is oxygenated with O2 saturated artificial blood across the villous membrane during passage through the fetal circuit of the placenta, which is placed in a specially constructed artificial uterus. Human term placentas were obtained immediately after vaginal delivery and used for the experiments. The gas transfer performance of the current apparatus was 60 ml/min for O2 and 40 ml/min for CO2 at a blood flow rate of 1.0 L/min. From these results (and the assured blood compatibility of the placenta), the authors conclude that this system will become one of the most promising modalities for prolonged extracorporeal oxygenation.

Biocompatible Materials↗

Continuous monitoring of artificial heart pump performance.

Continuous monitoring of pump performance is essential and effective for optimal driving of a pulsatile blood pump. The authors contrived a practical method for continuous estimation of blood volume in a pump by measurement of electrical impedance (Z). This method was evaluated with the air-driven, diaphragm type pump. The pump was made from polyurethane and had two metal connectors at the inlet and the outlet ports. Z was measured by charging the alternating current (50 kHz, 0.4 mA) between two connectors as electrodes. In in vitro tests, Z reached maximum value during full-empty and minimum value at full-fill. The blood volume calculated by an empirical equation of Z was linearly related to the real blood volume (r = 0.99). In in vivo tests with goats, pump output estimated by this method was linearly related to pump output measured with an electromagnetic flowmeter and effectively evaluated pump performance. For calibration, this method needed only to measure Z at full-fill. This method was useful as a controller of a full-fill to full-empty drive. It was concluded that this method is a practical estimate of pump performance, even if implantable diaphragm type pumps are used, and easily applicable to any kind of pulsatile pump.

Animals↗

A VAD and novel high performance compact oxygenator for long-term ECMO with local anticoagulation.

A novel method of long-term ECMO was designed and evaluated experimentally. Special features of this ECMO method include: 1. using a pneumatic diaphragm type VAD with excellent blood compatibility as a pump system; 2. using a newly developed, high performance, compact oxygenator, with a novel gas exchange membrane in which micropores are blind at the blood contacting surface; 3. regional anticoagulation within the ECMO circuit with short-acting protease inhibitor FUT-175; and 4. right heart bypass with direct cannulation through a thoracotomy. Four goats implanted with a VAD between the right atrium and the pulmonary artery underwent ECMO by interposing a compact oxygenator in the return cannula for as long as 14 days. Blood clotting was regulated with continuous infusion of FUT-175 from the inflow cannula of the ECMO circuit. In this system, 2 to 4 L/min of bypass flow, 80 to 120 ml/min of O2, and 40 to 80 ml/min of CO2 gas exchange were obtained. Serum leakage in the oxygenator did not occur, and various blood chemical and hematologic parameters were maintained within the normal range. Regional anticoagulant therapy was successfully achieved with a significant difference of activated clotting time between the blood samples from the systemic circulation and those from the ECMO circuit. These results indicate that this method overcomes several problems with ECMO, and has the capacity for long-term respiratory assistance.

Animals↗

An electrohydraulic total artificial heart with a separately placed actuator.

An electrohydraulic total artificial heart (EHTAH) system, consisting of a separately placed actuator and blood pumps with good anatomic fit, was designed. In the actuator is a brushless DC motor sandwiched between two metal bellows or two pusher-plate pumps connected with the blood pumps by polyvinylchloride tubes. A roller-screw system coupled with the bellows is used for alternative pumping, and silicone oil transmits the action. The pumps are elliptical, and the right pump has a flatter and longer shape than the left to fit the extremely short distance between the right atrium and the sternum. To evaluate in vivo performance, the pumps were implanted as a pneumatic system in a calf weighing 53 kg and three goats weighing 54-55 kg. The pump fit well in the animals, and the calf survived for 111 days, and one goat was alive for 8 days. The EHTAH system could provide an output of 6 L/min with pusher-plate pumps as oil chambers on in vitro evaluation. This system could become one of the most suitable approaches for a totally implantable system.

Animals↗

Chronic in vivo evaluation of a portable electrohydraulic ventricular assist system with a linear actuator.

Chronic experiments of the electrohydraulic ventricular assist system with a linear motor actuator were performed in two goats weighing 54 kg and 56 kg, and the system was used for more than 30 days. The actuator was designed to be fixed on the goat's back with a saddle. The pump was connected between the left atrium and descending aorta and placed paracorporeally on the chest wall. Linear action of an actuator bellows was delivered by silicone oil in a U-shaped polyvinylchloride tube to activate the pump. The maximum output in the 56 kg goat was 5.0 L/min. Goats could stand and sit freely. The first goat with a pusher-plate type pump died on the fifth day because of thromboembolism, but the second goat with a diaphragm type pump survived for 42 days. Blood chemistries remained within normal limits. Pump control was easy in both the duty-control mode and the stroke-control mode. With the automatic negative pressure control (ANPC) to prevent atrial wall sucking, the left atrial pressure was kept within +/- 10 mmHg, although left atrial pressure sometimes went below -80 mmHg without ANPC. Considering reliability, automaticity, and portability, the electrohydraulic ventricular assist system has become another choice for a practical, electrically driven ventricular assist system.

Animals↗

A composite driving system for LVAS and IABP: practical and effective driving and weaning.

We have devised a new method, termed alternate synchronous driving (ASD), to wean patients from a left ventricular assist system (LVAS) to a pressure assist intraaortic balloon pump (IABP). We have built a new drive unit, VCT200, to apply ASD easily and automatically. After IABP insertion in the final weaning stage, this method drives the LVAS and IABP alternately, with electrocardiogram (ECG) synchronization. The pumping ratio of IABP increases while that of LVAS decreases according to recovery of natural heart function. In in vitro studies, ASD was effective when bypass flow (BF) was less than 50% of total flow (TF) (TF:BF + cardiac output [CO]), and its advantages increased under lower BF conditions. Mean aortic pressure (mAP) and CO increased 10 mmHg and 15%, respectively, with this method (IABP:LVAS = 1:1) when BF was 30% of TF. During in vivo studies, mAP increased 75.7 +/- 6.7 mmHg to 80.1 +/- 3.6 mmHg (p less than 0.001), and the CO increased from 3.1 +/- 0.5 L/min to 3.3 +/- 0.5 L/min (p less than 0.001), while the endocardial viability ratio (DPTI/TTI) increased 20-30%. This method was used in a 62-year-old man in which LVAS was applied after ventricular aneurysmectomy, BF was reduced from 2.2 L/min to 1.1 L/min by using ASD without any change in systemic perfusion. This reduction of BF could not be achieved with LVAS alone. From these data, this system could wean patients from LVAS and then switch to IABP smoothly, easily, and automatically, without hemodynamic instability.

Combined Modality Therapy↗