Difficulties and hope in artificial organ research.
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Biomedical subjects
Publications and source records attributed to T Akutsu.
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Distribution of velocity, viscous shear stress and turbulence intensity in the wake of several mechanical heart valves is studied using a laser Doppler anemometer system during steady and pulsatile flow conditions. The corresponding results are also obtained for a sharp-edged orifice which help assess changes in the flow pattern caused by different valve geometries. The results are correlated with the static pressure drop across the valves and its recovery in the wake, as a function of the Reynolds number. Results suggest a substantial increase in turbulence intensity, in some cases by as much as 40- to 50-fold, thus raising a possibility of thromboembolism.
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Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.
We studied three patients with internal carotid artery occlusion at the siphon who had recanalization during 1 month of close observation. Angiography and duplex carotid sonography (DCS) were repeated serially in each patient. Blood flow patterns detected by DCS were classified into three patterns by specific angiographic changes. The distal occlusive flow pattern on DCS corresponds to internal carotid artery occlusion at the siphon angiographically, the median flow pattern on DCS corresponds to partial recanalization, and a normal flow pattern on DCS indicates almost complete recanalization. Since DCS can be easily repeated, the exact time of recanalization can be determined noninvasively. In all three patients, hemorrhagic infarction observed on computed tomograms occurred at the time of recanalization detected by DCS. DCS demonstrates that recanalization is one of the mechanisms of hemorrhagic infarction.
Islets were microencapsulated in agarose gel for examination of the possible use of microencapsulated islets as a bioartificial pancreas. Microencapsulated islets secreted insulin into the culture medium (RPMI-1640) and could rapidly increase their insulin release in response to a glucose challenge even after greater than 100 days. Hamster islets in groups of 400-1000 encapsulated in microbeads containing 11-14% (wt/wt) agarose were xenogenically transplanted into the peritoneal cavity of five diabetic mice. The longest normoglycemic period in these mice was 53 days, which was markedly longer than the normoglycemic period obtained by nonencapsulated islets. Agarose seems to be a suitable basic material for encapsulating islets, because the islets can easily be microencapsulated without any adverse effect on the islet function.
One of the most important characteristics of a ventricular assist device (VAD) is good antithrombogenicity such that the circulating blood does not clot on the surface even when the bypass flow through the device is reduced at the time of weaning-off. A pneumatic and diaphragm-type VAD with excellent antithrombogenicity was developed for clinical use. The pump is made of Japanese-made segmented polyether polyurethane and the maximum output is 7.0 L/min. If the bypass flow was maintained above 2.0 L/min during early postoperative period, thrombus formation was rarely observed even when the flow rate decreased afterwards in chronic animal experiments using 30 goats. Experimental analyses suggested that a biolization mechanism of the material surface covered by absorbed plasma protein might play a major role in the establishment of antithrombogenicity of the pump. No mechanical failure, thrombosis, calcification, and complication in experimental animals occurred when the VAD manufactured under our good quality control system was driven adequately. These results proved that the VAD could be used reliably for at least 3 months. In conclusion, the VAD is safely applicable to clinical cases and contributes to treatments of profound heart failure patients.
Recently, various types of left ventricular assist systems (LVAS) have become available to treat the patients in profound heart failures beyond the limit of the effects of IABP. However, the occurrence of an intractable severe bi-ventricular failure, ventricular fibrillation (VF) or cardiac arrest during the time with left ventricular assistance became a more serious problem. Since during the usage of these assist devices, pulmonary venous return will decrease, consequently, LVAS will not be able to maintain sufficient systemic circulation over a extended duration. This study was intended to develop a method of prolonged circulatory maintenance only with a LVAS in cardiac arrested goats until the time when heart transplantation will be performed. In this study, our LVAS was implanted between the left atrium and the aorta in twelve goats in which the hearts were fibrillated. We have followed the principle of circulatory maintenance only with our LVAS in cardiac arrest based on the pressure gradient between the right and left atria and at the same time the pump suction effect through the lungs. The results showed that when pulmonary vascular resistances (PVRs) were kept within normal ranges (less than 15,000 dynes.sec.cm-5), systemic circulations were well maintained only with LVAS as long as RAPs were kept in 14-18 mmHg. Under these conditions, the systemic circulatory flows have fluctuated between 80-140 ml/kg/min depending on the animals demands. The mean arterial pressures were kept above 80 mmHg and the goats have shown quite normal behaviors. However, in goats which showed the presence of pleural effusions and ascites were found to be more difficult to maintain prolonged normal circulation. In our study, the maintenance of total serum protein level above 6.0 g/dl was found to be essential to prevent the development of both pleural effusions and ascites . The authors have achieved the longest survival goat for a duration of 38 days after implantation with our LVAS. We have concluded that when PVRs may be kept in normal ranges, our LVAS can maintain normal systemic circulation even in arrested hearts for a prolonged duration during which time heart transplantation or total artificial heart replacement can be performed.
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For continuous measurement of both SO2 and [Hb] of whole blood, a hybrid type optical sensor was developed, tested in vitro and applied to the continuous measurement of arterial and mixed venous SO2 and [Hb] of awake live animals whose circulation was entirely supported by a pair of artificial hearts. The purpose of using artificial hearts was to control the cardiac function precisely and to obtain independent responses of the peripheral circulatory system. Both sensors in the arterial and venous circuits functioned satisfactorily for a duration of 40 days; no blood clots were observed around the sensor and the mixed venous SO2 varied sensitively in response to changes in the respiratory status, pump output, [Hb], and oxygen consumption, thus showing that it could be used as an indicator to evaluate the adequacy of oxygen delivery to peripheral tissues.
Seven canine donor hearts in which atrial septal defect and tricuspid regurgitation had previously been produced were heterotopically transplanted into the recipients' chest cavities. Indium-111 antimyosin myocardial imaging of the excised heart was performed using a scinticamera. Magnetic resonance imaging was also performed and the T2 relaxation time calculated. Subsequently, these data were correlated with pathological findings, which indicated the degree of rejection. Indium-111 antimyosin uptake was high in moderate and severe rejection, but the T2 relaxation time was prolonged even in mild rejection. Thus indium-111 antimyosin uptake was specific, and the T2 relaxation time was sensitive, for detecting the severity and extent of cardiac rejection. Although ex vivo experimental results have been reported, these new methods allow characterisation and accurate evaluation of myocardial tissue undergoing cardiac rejection.
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Pneumatically driven left ventricular assist devices (LVADs) were acutely implanted between the left atria and the descending aortas of dogs, and were driven in five pumping modes: electrocardiogram synchronous modes with the duty factors of 1:1, 2:1, and 4:1, and asynchronous modes with the pulse rates of 60 and 80 beats/min (bpm). The ventricular diameter and myocardial segment length were measured by an ultrasonic displacement meter and implantable miniature sensors. Bulk mechanical work of the left ventricle and regional mechanical work of the myocardium were calculated from these dimensions and the left ventricular pressure. LVAD reduced the bulk mechanical work of the left ventricle by 30-50% and the regional work by 30-60%. The mean aortic pressure and the total flow (= aortic flow + pump bypass flow) were highest in the 1:1 synchronous pumping mode, which indicates that this mode is most effective to maintain the systemic circulation and coronary blood flow. Asynchronous pumping and synchronous pumping with 2:1 duty factor were most useful to reduce the mechanical work of the left ventricle.
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It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement.