Biomedical subjects
Publications and source records attributed to Y Abe.
We describe a case of olfactory neuroblastoma diagnosed by 99mTc-ECD SPECT. Although MRI and CT are very important for delineating these tumors, they are, by no means, specific for neuroblastomas. 131I-MIBG scintigraphy, the standard method for imaging tumors of neural crest origin, also failed to detect a histologically proven esthesioneuroblastoma.
Atrial natriuretic peptide (ANP) was administered intravenously to three goats at a dose of 0.1 micrograms/kg/min for 40 min both before total artificial heart (TAH) placement and at 1, 7, and 14 postoperative weeks to determine whether exogenous ANP exhibits the same effect on animals with TAHs as it does on normal animals. No significant changes in the increases in plasma levels of ANP and cyclic guanosine monophosphate (c-GMP) were observed during ANP administration after TAH insertion. In preoperative animals, urine volume and urinary sodium excretion increased greatly during ANP administration, but this natriuretic effect was strongly suppressed in TAH animals. The changes in the decreases in arterial pressure and in central venous pressure (CVP) or right atrial pressure that occurred during the administration of ANP were not significant either pre- or post-operatively. Thus, only the natriuretic effect of ANP on the kidney was significantly suppressed in TAH animals, which might be due to some down-regulation of ANP receptors in the kidney, the production of some antagonists of ANP, sympathetic hypertonicity, or the elevation of CVP.
The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use.
A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.
An artificial heart (AH) driving system, in which a sac or diaphragm type blood pump is liquid gas driven, is designed. The working mechanism of this system is as follows: 1) liquid gas is used for the driving source; 2) a liquid gas is stored in its liquid state in the circuit; 3) a liquid gas is vaporized, and the vaporizing pressure squeezes the blood pump, causing ejection of blood; 4) vaporized gas is aspirated and compressed by a small compressor to liquefaction through the heat exchanger, then negative pressure is applied to the blood pump and blood is aspirated; and 5) the blood pump is driven in this closed cycle. To demonstrate the mechanism of this system, a prototype was developed using Freon 114 as the liquid gas. In this system, the maximum flow of the AH at a 100 pulse per minute rate, was about 6.9 L/min, using a 90 ml sac type blood pump. The advantages of this AH driving mechanism are as follows: 1) a small system is available because pressure chambers are not necessary; 2) a biventricular system is available, with a single compressor; 3) no compliance chamber is necessary if the system is small enough to be implanted.
The purpose of this study was to clarify whether plasma ANP levels (p-ANP) are abnormal in TAH animals, and if ANP plays an important role in circulatory failure in TAH animals. In five TAH goats that survived for 51-171 days, changes in hemodynamic parameters, plasma levels of renin, angiotensin I and II, aldosterone (p-RAA), and p-ANP were measured, and correlations between p-ANP and other parameters were studied, and histologic study of ANP and assay of the ANP content in atrial tissue was undertaken. Generally, p-ANP of TAH goats fell temporarily after surgery but then recovered to preoperative levels. Histopathologic studies of atrial tissue and ANP granules proved almost normal, although the coronary blood supply was occluded for more than 170 days; the ANP content in the atrium did not show significant changes after 51 days of TAH pumping. In one case prominent correlations between p-ANP and p-RAA were observed, and in another case significant correlation between p-ANP and arterial pressure was observed. However, these correlations were not observed in every case. In TAH goats the plasma ANP level did not increase in spite of high atrial pressures. Plasma ANP levels in TAH animals are almost normal. In TAH animals no role in the pathogenesis of hemodynamic abnormalities is played by abnormality of plasma ANP levels. However, TAH animals may display an abnormality in sensitivity to the p-ANP.
The natural heart could be preserved in the beating state, with appropriate afterload, for more than 24 hrs if supported by blood compatible artificial organs and biomedical engineering techniques. An artificial environment was developed using this philosophy. The system was constructed from four subsystems: circulatory, respiratory, metabolic, and environmental. In the circulatory subsystem, diastolic pressure was held at 70 to 100 mmHg by computer aided peripheral resistance, and a left ventricular assist device (LVAD) could be added when cardiac function was weakened. The respiratory subsystem was composed of an artificial lung and computer aided gas mixer for O2, CO2, and air, which kept blood PO2 and PCO2 within physiologic levels. In the metabolic subsystem, glucose and insulin were injected by infusion pump so as to maintain blood sugar within 100 to 200 mg/dl, whereas the environmental system preserved the isolated heart at 37 degrees C in a sterile water bath. Goats' hearts were connected to this system, and continued to beat for a maximum of 24 hours.
No control method has yet been established for the total artificial heart (TAH) during exercise. As the simple intrinsic control method does not significantly increase cardiac output (CO), this study attempted to develop a new TAH control method that increases the CO during exercise in a manner similar to a natural heart (NH) by predicting changes in CO as a time function (TF) at various treadmill speeds. The control method for TAH was as follows: 1) an arbitrary grade of treadmill exercise was loaded onto the TAH goat; 2) a TF at this grade of treadmill exercise was determined from the physical activity rate (PAR) measurement, defined as the time average of the increase in vertical acceleration of the body; 3) operating parameters of both pumps were controlled in accordance with the TF using the computer algorithm. With the predictive control method changes in CO in the TAH were almost the same as in the NH, whereas no increase in CO occurred with the fixed control method (FC), in which operating parameters remained unchanged during exercise. Changes in blood lactate and catecholamines tended to be less than with the FC.
Bjork-Shiley and Hall valves used in most artificial heart blood pumps have often induced problems, which include 1) An expensive valve must be used even when the AH is used for only a few days, 2) Ring thrombus was often formed at the interface between the valve ring and blood pump, seamless fabrication was not possible, and 3) Mechanical failure often occurred. To improve these circumstances, a new jellyfish valve was designed and manufactured. The valve has a simple structure: The center of a thin circular polyurethane membrane is fixed on a polyurethane base plate, which has many holes or slits to reduce flow resistance and help hold the membrane during the diastolic phase. In a mock circulation study, the valve displayed performance similar to the Bjork-Shiley valve. A small amount of regurgitant flow was observed at valve closure, in comparison with the Bjork-Shiley valve. It was recognized in the flow visualization study that the central region of the membrane was washed out well by the flapping of the membrane. This jellyfish valve is promising for use in a AH blood pump.
The effects of an angiotensin converting enzyme inhibitor, SA-446, on regional hemodynamics were examined in conscious renal and spontaneously hypertensive rats (RHR, SHR) using the radioactive microsphere method. We observed the differences in regional hemodynamics between hypertensive rats and normotensive rats, as well as the differences between SHR and RHR. An i.v. administration of SA-446 at a dose of 1 mg/kg induced a considerable hypotension in both types of hypertensive rats and increased the flow rates in most organs, along with an increase of cardiac output. The systemic and regional hemodynamic changes due to SA-446 in SHR and RHR were not qualitatively different, but the organs in RHR responded to SA-446 with greater magnitude. SA-446 increased the flow rates in organs which originally had low flow rates, more than it increased those of normotensive control rats.
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To date, no one has conclusively accurately measured the regional bone blood flow mainly due to the lack of a proper investigative method. In this study, regional blood flow in the femur and tibia in adult mongrel dogs were studied using 85Sr-and 141Ce-labeled microspheres with a diameter of 15 +/- 5 microns. The blood flow rates were calculated by relating the radioactivity from tissue samples that from sample blood with a known flow. The highest rate of blood flow, 48.7 ml/min/100 g, was found in the femoral marrow and the lowest, 3.0 ml/min/100 g, in the diaphyseal cortex of the tibia. Flow rates in the metaphyseal regions, about 15 or 20 ml/min/100 g, were one and a half or 2 times greater than those in the epiphyseal regions. These values were mostly within the range of values reported by other investigators. Radioactive microspheres can be applied not only to physiological conditions but also to various pathological conditions if their size and the dose, the site and method of injection and tissue sampling are investigated further.
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This study concerned 18 cases of value replacement in patients than 15 years, between 1964 and 1980. In this period, there was a total of 30 such cases, but there were eight hospital deaths and four cases with less than two years postoperative observation. These 12 cases were excluded from the study. The average follow-up period of the 18 cases was eight years and nine months. During this period, six cases were associated with postoperative complications, which consisted of three cerebral emboli, two malfunctions of the implanted prostheses and one congestive heart failure. Three cases involved prosthesis-related death. Secondary implantations were performed in two cases; one for relative stenosis of the prosthesis and the other for calcification of the porcine xenograft. Physical activity in the 15 survivors has been excellent in all but two cases with arrhythmia and sequelae of cerebral damage due to surgery.
Three-dimensional finite element analysis and Weibull analysis were used to evaluate the effect of the thickness and the rigidity of the retainers on the risk of failure of an anterior resin-bonded prosthesis. Retainer thickness ranged from 0.4 to 1.4 mm. The physical properties of metals similar to Ni-Cr and type IV gold alloys were used. A concentrated load (100 N) was applied to the incisal edge of the finite element analysis modeled pontic, and the data of other loads (150 to 500 N in 50-N increments) were calculated from the data of 100 N. Subsequent Weibull analysis revealed that failure probability diminished when there was an increase in metal thickness at loads of 300 to 350 N, particularly for the retainer made of a type IV gold alloy. The reduction in failure probability caused by increasing the thickness of the metal was greater when type IV gold alloy was used than when Ni-Cr alloy was used. This investigation suggests that the longevity of resin-bonded retainers can be prolonged by thickening the retainers, rather than using more rigid metals.
We examined the Ki-ras oncogene point mutation in primary tumors and tumor xenografts as a marker of genetic stability. We detected point mutations at codon 12 of the Ki-ras oncogene in 21.3% (17/80) of the tumor xenografts as well as 21.0% (17/81) of the primary human neoplasms. The mutation from GGT (glycine) to GAT (aspartic acid) was the most frequent mutation in the tumor xenografts (64.7%, 11/17) as well as in the primary human neoplasms (64.7%, 11/17). The point mutation at codon 12 of the Ki-ras gene showed no discrepancy between the original human neoplasms and their xenografts in all 19 cases. The findings suggested that the point mutation at codon 12 of the Ki-ras gene was very stable in human neoplasms and their tumor xenografts through serial transplantation.
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