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Biomedical subjects

H Oku

Publications and source records attributed to H Oku.

At least 73 records · Page 4Linked to original sources

Experimental orthotopic heart and bilateral lung transplantation completed without cardiopulmonary bypass.

INTRODUCTION: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass. METHODS: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed. RESULTS: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (+/- SD) ischemic time was 67 +/- 11 min with a mean (+/- SD) anastomotic time of 54 +/- 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 microg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function. CONCLUSIONS: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed "off pump" can be technically feasible without the loss of cardiac and pulmonary functions.

Anastomosis, Surgical↗

Extracardiac total cavopulmonary connection via an atrial and pericardial tunnel.

We performed extracardiac total cavopulmonary connection using only native tissue in two patients with complex heart disease. The extracardiac lateral tunnel was constructed from pedicled autologous pericardium and atrial wall During follow-up both patients remained in the New York Heart Association functional class I and demonstrated normal sinus rhythm. These modifications not only avoid the risk of potential postoperative complications due to artificial materials, but also allow growth of the conduit.

Angiography↗

[A successful surgical repair of mitral stenosis and regurgitation with pulmonary arteriovenous fistula].

The patient was a 74-year-old man who was complained cyanosis and shortness of breath on exertion. He had undergone open mitral commissurotomy for mitral stenosis 19 years previously. He was diagnosed with mitral stenosis and regurgitation combined with pulmonary arteriovenous fistula (PAVF). Moderate pulmonary hypertension was also observed. It appeared that the PAVF was located where one-step operation with open heart surgery was anatomically feasible, and that his condition would be improved by resection of the fistula and decreasing overload of left atrium by mitral valve replacement. One-step operation including mitral valve replacement and tricuspid annuloplasty with enuculation of the PAVF was therefore performed. The patient has done well postoperatively, and postoperative cardiac catheterization revealed no increase in pulmonary arterial pressure.

Aged↗

Osteopathy in broiler chicks fed toxic mimosine in Leucaena leucocephala.

Further studies of mimosine toxicity in broiler chicks were done to clarify a possibility of osteopathy. The mineral content and density of femur and the strength, ductility, and toughness for the index of mechanical properties significantly decreased in the 1% mimosine group, compared with those in the control and restricted groups. The stiffness had a decreasing tendency in the 1% mimosine group. Consequently, it was concluded that chicks fed ad libitum a 1% mimosine diet for 12 days developed osteopathy. The bone mineral density and the strength of the restricted group were lower than those of the control group, and those of the 1% mimosine group were still lower than those of the restricted group. Contents of pyridinoline and deoxypyridinoline in the excrement were significantly higher in the restricted group than those in the control group, but the contents in the 1% mimosine group were significantly lowest among the groups. Osteopathy in chicks fed mimosine, therefore, seemed to be done by loss of appetite and changing to a low turnover of bone caused by mimosine.

Amino Acids↗

NADH-dependent inhibition of branched-chain fatty acid synthesis in Bacillus subtilis.

Addition of NADH to crude but not to pure branched-chain alpha-keto acid decarboxylase decreased the CO2 production from alpha-keto-beta-methylvalerate (KMV) suggesting the presence of an NADH dependent inhibitor in the crude enzyme from Bacillus subtilis. This NADH-dependent decarboxylase inhibitor was purified to homogeneity by a fast protein liquid chromatography system. The purified inhibitor was identical with leucine dehydrogenase as to N-terminal amino acid squence (35 residues) and molecular weight, and catalyzed the oxidative deamination of three branched chain amino acids (BCAAs), valine, leucine, and isoleucine. The decarboxylase inhibitor was therefore identified as leucine dehydrogenase. A decreased substrate availability caused by leucine dehydrogenase thus reasonably accounted for the NADH dependent inhibition of the decarboxylation. In turn, the observation that leucine dehydrogenase competes with the decarboxylase for branched-chain alpha-keto acid (BCKA) suggested an involvement of this enzyme in the branched chain fatty acid (BCFA) biosynthesis. This view was supported by the observation that addition of NAD to crude fatty acid synthetase increased the incorporation of isoleucine into BCFAs. Pyridoxal-5'-phosphate and alpha-ketoglutarate, cofactors for BCAA transaminase, modulated BCFA biosynthesis from isoleucine in vitro, suggesting also the involvement of transaminase reaction in BCFA biosynthesis.

Acyltransferases↗

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (4). 6-month repeated dose intravenous toxicity study in rats with 1-month recovery test].

A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg. ONO-5046.Na did not affect clinical signs, body weight, food consumption, opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na in rats is 75 mg/kg/day for both sexes in this study.

Animals↗

[The left ventriculectomy (Batista procedure) in a patient of the dilated cardiomyopathy: a report of the first successful case in Japan].

We presented a case of 18-year-old male with dilated cardiomyopathy undergoing surgical left ventricular volume reduction (Batista procedure). He seemed to be the first successful survivor after the procedure in Japan. In the follow up study, cardiac function and clinical status of the patient have been moderately improved. Batista procedure seems to be an attractive choice to treat end-stage heart failure in Japan where the option of treatment for this particular situation is limited.

Adolescent↗

Prolonged hypothermic cardiac storage with histidine-tryptophan-ketoglutarate solution: comparison with glucose-insulin-potassium and University of Wisconsin solutions.

BACKGROUND: The purpose of this study was to compare the efficacy of histidine-tryptophan-ketoglutarate (HTK) solution after prolonged cold storage with that of the conventional glucose-insulin-potassium (GIK) and University of Wisconsin (UW) solutions in experimental heart preservation. GIK solution was chosen as a control to mimic current clinical regimens. Variables of cardiac function, myocardial tissue water, and adenine nucleotide pool metabolites were used to assess prolonged myocardial preservation in the isolated rat heart model. METHODS: Hearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline cardiac function. The hearts were divided into three groups (n=6 per group) according to each preservation solution used: group 1, GIK solution; group 2, UW solution; and group 3, HTK solution. The hearts were then arrested and stored in each solution for 6, 8, and 12 hr at 4 degrees C. After storage, the hearts were reperfused and recovery of cardiac function and myocardial tissue water content were evaluated. Myocardial adenylate contents just after storage in each group (n=5 hearts/group) were also measured. RESULTS: The hearts stored in HTK solution showed maintenance of cardiac function at up to 8 hr of almost 80% of prepreservative baseline function; however, recovery of cardiac function of the hearts stored in UW solution revealed an initial loss of function at 6 hr of almost 60% and a decline to 50% at 8 hr. Furthermore, recovery of cardiac function of the hearts stored in GIK solution revealed a progressive loss of function at 6 hr of storage of almost 50% and a decline to 30% at 8 hr of storage. The myocardial ATP/ADP ratios after 6 hr of storage in HTK and UW solutions were significantly higher than the ratio found in GIK solution. Although the myocardial ATP/ADP ratio after 8 hr of storage in HTK solution was maintained above 50%, the ratios in GIK and UW solutions declined to 15%. In addition, the myocardial energy charge values of the hearts stored in HTK solution were sufficiently maintained until 8 hr of storage, whereas the values in UW and GIK solutions declined to below 50% at 6 hr of storage and 20% at 8 hr of storage. Although there were no significant differences in tissue water contents after 6 and 8 hr of storage among the three groups, the water contents of the hearts after 12 hr of storage in HTK and UW solutions were significantly lower than that of the hearts stored in GIK solution. CONCLUSIONS: Our results suggest that HTK solution is much more effective than UW and GIK solutions for isolated rat heart preservation; however, successful cold storage of the heart is highly energy-dependent, and a dramatic breakdown of myocardial energy level, which causes a crucial decline in cardiac function, occurs between 8 and 12 hr of storage.

Adenosine↗

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

6-Ketoprostaglandin F1 alpha↗

Two-directional aortic annular enlargement for aortic valve replacement in the small aortic annulus.

We have encountered 3 patients with a small aortic annulus for whom the conventional posterior enlargement alone was not extensive enough to implant an artificial valve of acceptable size. Therefore, we performed two-directional enlargement, which is a combination of posterior and anterior enlargement. First, the posterior enlargement was done, and then an additional aortotomy was made anteriorly and extended to the ventricular septum. The aortic annulus was enlarged by 68% after the two-directional enlargement. At a follow-up of 31 months, the patients' functional status was New York Heart Association class I.

Adult↗

Reconstruction of right ventricular outflow tract by pedicled pericardial valved conduit.

A modification of the Rastelli technique using a pedicled autologous pericardial valved conduit was performed on 3 patients aged 10 months to 3 years. Two patients in whom a prosthetic gusset was not used or was partially used showed good recovery during the follow-up period (3 months to 3 years). The pedicled autologous pericardial conduit may be expected to increase its diameter with physical growth.

Child, Preschool↗

Single lead atrial synchronous ventricular pacing in Japanese patients with complete atrioventricular block.

The purpose of this study was to review our experience with atrial synchronous ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.) using single atrioventricular leads in Japanese patients with complete atrioventricular block and normal sinus function. Twenty patients with a mean age of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the amplitude of atrial signals in the supine position during normal breathing, which was measured directly using an external pacing system analyzer, ranged from 1.8 to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4 +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the patients. During a follow-up period, the percentage of atrial synchronization was >95% in 19 patients, and none of the patients had pacemaker related tachycardia or pacemaker related complications. These results were promising enough to warrant the extension of the clinical use of the VDD pacemaker.

Adult↗

Timing of surgical treatment for active native value endocarditis.

The aim of the study was to assess the optimum timing of surgical treatment for the active phase of native valve endocarditis. A retrospective study was conducted of the records of patients who had undergone aortic and/or mitral valve replacement for active native valve endocarditis during 1979-94 at Kinki University Hospital. Thirty-three patients with active infective endocarditis of the native valves were treated surgically. Their mean age was 45.4 years (range 11-71). The infective organism was streptococcus in 9 cases, Staphylococcus aureus in 8, and enterococcus in 4 cases. Blood cultures were negative in 9 cases. Of the patients infected with Staphylococcus aureus, 3 died soon after the operation and 1 died later during hospitalization. These 4 patients had been treated medically more than 2 weeks before operation. Another patient who was also treated medically more than 2 weeks before surgery survived. In contrast, all 3 patients infected with Staphylococcus aureus who were operated on within 2 weeks after the onset survived. No early or in-hospital deaths were documented among patients infected with organisms other than Staphylococcus aureus. Among patients who had suffered preoperative embolic episodes, the time from the initial pyrexia to the embolic event was clearly shorter in those infected with Staphylococcus aureus than in those infected with other organisms. Among the former group, 5 out of 6 patients suffered an embolism within 2 weeks of the onset of pyrexia and the remaining 1 within 3 weeks. Thus, in patients presenting with active native valve endocarditis caused by Staphylococcus aureus, surgical treatment should be performed as soon as possible after the onset of pyrexia, preferably within 2 weeks or as soon as the infective organism is identified as Staphylococcus aureus.

Adolescent↗

Apolipoprotein A-1 of Japanese quail: cDNA sequence and modulation of tissue expression by cholesterol feeding.

Apolipoprotein (apo) A-1 cDNA was amplified by the reverse-transcriptase-polymerase chain reaction (RT-PCR). Primers were synthesized according to the nucleotide sequence of chicken apo A-1, and the identity of apo A-1 cDNA was confirmed by comparing with the N-terminal amino acid sequence. The open reading frame of apo A-1 cDNA consists of 795 nucleotides, and it is capable of coding a polypeptide of 264 amino acids. A comparison between quail and chicken apo A-1 revealed 94.5% homology in the nucleotide sequence and 91.7% homology in the amino acid sequence. There was a similar 11- or 22-amino acid repeat in quail apo A-1 as was the case for chicken apo A-1. Apo A-1 mRNA was evaluated to be 1.4 k in length and was expressed in various tissues of Japanese quail: the liver, small intestine, lung, kidney, heart, and muscle. A quantitative evaluation, however, revealed that the liver and small intestine were the major organs for apo A-1 synthesis, accounting for more than 90% of the total expression of apo A-1 mRNA. Besides apo A-1 mRNA (1.4 k in length), a transcript of 4.1 k was detected in all the tissues examined, with a magnitude ranging from 5 to 10% of the apo A-1 mRNA level. The effect of cholesterol level on the expression of apo A-1 mRNA was studied to address the physiological significance of apo A-1 in the liver, small intestine, and muscle. The level of cholesterol in the liver and breast muscle was increased by feeding with cholesterol and reached a saturation level at day 7. There was also a temporal rise of cholesterol level at day 7 in the small intestine. Dietary cholesterol increased the expression of apo A-1 mRNA two fold in both the liver and small intestine. This was not the case for breast muscle, in which the expression of apo A-1 mRNA was not modulated by the cholesterol level.

Amino Acid Sequence↗

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (1). Fertility study in rats].

A fertility study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to males from the 64th day before mating until necropsy, and to females from 15th day before mating until day 7 of gestation, at a dose level of 0 (control), 25, 50 or 100 mg/kg/day. On day 20 of gestation, all dams were sacrificed and their fetuses were examined. In the 100 mg/kg/day group, hypoactivity, clonic convulsion, bradypnea/apnea and redish lacrimation were observed after administration in both sexes, and 3 males and 2 females died. Reddish lacrimation was occasionally seen in males at late stage of the treatment period in 50 mg/kg/day group. In the 100 mg/kg/day group, body weight gain suppressed in females from the premating through the gestation period, and food consumption decreased in females during the premating period, and mean thymus weight decreased in males. ONO-1101 did not affect estrous cycle, copulatory or fertility in both sexes or external, skeletal or visceral features of the fetuses. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for general toxicity in parents, and 100 mg/kg/day for the reproductive performance in parents and for the development of fetuses.

Adrenergic beta-Antagonists↗

Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone Japanese quail.

The purpose of this study was to characterize the lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and commercially available (CA) Japanese quail were fed either a semi-purified diet containing 1% cholesterol or a cholesterol-free diet for two weeks. The lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The lipoprotein distribution patterns obtained from both strains showed an HDL-predominant pattern. A protein of 26 kDa was the major apoprotein in the entire density range of the lipoprotein class. Marked increases in the cholesterol ester levels were observed in the lower density fractions (1.006 < d < 1.055: chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46% of the total lipids in CA quail and 54% in HAP quail. In addition, the presence of a protein of 470 kDa was exclusively observed in the lower density fractions (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions of the chylomicron and VLDL fractions were affected by the dietary cholesterol in both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight %). However, cholesterol feeding had no effect on the level of cholesterol, chemical composition or fatty-acid composition of the HDL fractions in either strain. Although the lipoprotein and apoprotein profiles of HAP quail showed resemblances to those of the CA quail, expression of the 470 kDa protein in the lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was discussed in this study.

Animals↗