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Biomedical subjects

T Takasugi

Publications and source records attributed to T Takasugi.

At least 55 records · Page 3Linked to original sources

Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a significant rise in arterial PO2 from 84 to 99 Torr. The findings are highly compatible with the idea that HPV is distinctly attenuated in diseases areas induced by oleic acid probably due to a local accumulation of vasodilator prostanoids. Inhibiting prostanoid biosynthesis may selectively enhance the vascular reactivity to O2 in shunt vessels and may redistribute the perfusion from shunt to relatively normal areas, thereby improving gas exchange at alveolar region without altering the total amount of extravascular lung water.

Animals↗

[Alteration of oxygen extraction and blood flow in various organs under acute hypoxia].

To assess the compensatory mechanisms involved in maintaining aerobic metabolism in various organs during exposure to acute hypoxia, five anesthetized and paralyzed dogs were ventilated with either normoxic (FIO2: 0.21) or hypoxic gas mixture (FIO2: 0.13). Under both conditions, we examined systemic and pulmonary hemodynamic parameters, and took samples of arterial and mixed venous blood as well as venous blood from various organs including the heart, brain splanchic organs (hepatic vein) and kidney. Based on PO2, PCO2 and pH values as measured with electrodes, we calculated O2 and CO2 contents in each blood sample. The values thus obtained were then used to estimate the O2 extraction ratio (ER), gas exchange ratio (R) and difference of base excess between arterial and venous blood (avBE) in the whole body as well as in each organ. In addition, both O2 delivery (DO2) and O2 consumption (VO2) in the whole body were calculated. Although the whole body showed a decrease in DO2 and an increase in ER during hypoxic gas breathing, other parameters including R, avBE and VO2 did not change significantly. Higher ER values were found in the heart and brain than those in the splanchic organs and kidney, the qualitative trend being the same irrespective of FIO2. On the other hand, increase in ER during hypoxic gas breathing was considerably larger in the splanchic organs and kidney than that in the heart and brain. There was no significant difference in R and avBE in any of the organs between normoxic and hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Distribution of ventilation and of diffusing capacity to perfusion in the lung.

We developed a method for estimating the distribution of ventilation (VA) and of diffusing capacity (G) to perfusion (Q) in the lungs. We used O2, CO2 and CO together with six inert gases of widely differing solubility and assumed that mass transfer efficiency of each gas in a gas exchange unit is limited by both VA/Q and G/Q ratios. The underlying lung model comprised 20 units along both the VA/Q and G/Q axes. Using numerical analysis, we transformed the data into a virtually continuous distribution of Q in the VA/Q-G/Q field. We tested the precision of the numerical procedure by examining the recovery of various artificial distributions, and found that distributions with up to two modes could be recovered with reasonable accuracy. Analytical results from 15 patients with interstitial pneumonia of unknown etiology (IPF) revealed the following features. (1) In an early disease stage, most of the lung was operating in the range of normal VA/Q, without a significant contribution of diffusion limitation. (2) An advanced stage of the disease exhibited a widening of VA/Q distribution and either broad unimodal or bimodal distribution of G/Q, extending to G/Q below 10(-3) ml (STPD)/(ml.Torr) with diffusion-limited O2 exchange. (3) Severe diffusion limitation causing disequilibrium of inert gas across the blood-gas barrier was observed in three (far advanced fibrosis; active interstitial inflammation) out of 15 patients. These findings suggest that inhomogeneity of G/Q does exist and may play an appreciable role in causing impairment of gas exchange in patients with interstitial pneumonia.

Animals↗

[Impairment of gas exchange in acute lung injury].

To demonstrate the characteristics of impaired gas exchange in acute respiratory distress syndrome (ARDS), an experimental model of lung injury was produced in 24 mongrel dogs by intravenously injecting 0.07 ml/kg of oleic acid. While allowing the animal to breathe a mixture of 0.1% CO in air, normal saline, which contained appropriate amounts of six inert gases such as SF6, ethane, cyclopropane, halothane, ether and acetone, was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were taken simultaneously. The concentrations of the nine indicator gases (O2, CO2, CO and six inert gases) in the samples were measured in terms of a gas chromatograph, permitting analysis of the distribution of ventilation to perfusion (VA/Q) as well as the diffusing capacity to perfusion (G/Q) in injured lungs. To determine the role of hypoxic pulmonary vasoconstriction (HPV) in maintaining gas exchange in ARDS, hemodynamic and gas-exchange parameters were investigated at inspired O2 concentrations (FIO2) of either 21 or 60%. The impairment of gas exchange was examined by measuring the fractional retention (R) of the inert gases in arterial blood. Furthermore, to assess the possible contribution of vasoactive prostanoids in regulating vascular reactivity in ARDS, observations at FIO2 of 60% were repeated after administered indomethacin at a dose of 5 mg/kg. Analytical results revealed that shunt flow in experimental dogs with lung damage caused by oleic acid averaged 17%. Furthermore, widening of VA/Q distribution was found accompanied with significant contribution of extremely low VA/Q areas. In addition, most of the lung was operating in G/Q units with values ranging from 10(-3) to 10(-2) but 9.8% of total Q(QT) was received by the area with G/Q less than 10(-3), which might limit O2 exchange between the alveolar gas phase and capillary blood. Although pulmonary vascular resistance (PVR) in injured lungs observed at FIO2 of 60% was significantly smaller than the value obtained at FIO2 of 21%, QT as well as extravascular lung water did not differ in the two conditions. The R value for the indicator gas was consistently lower at FIO2 of irrespective of gas species. Administration of indomethacin caused a considerable diminution of the R value for inert gas but a rise in PVR without an appreciable change of either QT or extravascular lung water. This was followed by a significant rise in arterial PO2 from 84 to 99 Torr.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Effects of SO2 and pH on blood-gas partition coefficients of inert gases.

Potential effects of SO2 and of pH on blood-gas partition coefficients, lambda, for inert gases, including SF6, ethane, cyclopropane, halothane, diethyl ether, acetone and N2, were systematically investigated using human blood. Measurements on lambda were performed at 37 degrees C in conditions of varied SO2 and pH using gas chromatography. Incorporating the experimental data on lambda, multiple inert gas elimination was applied to 18 patients with varied chronic lung diseases, in order to estimate the effects of SO2 and of pH on both inert gas exchange and resultant recovery of VA/Q distribution in the lung. For this purpose, the data obtained by the procedure of multiple inert gas elimination were analyzed with the classical approach but allowance was made for lambda of the indicator gas to vary according to exchange of O2 and of CO2 in the pulmonary capillary. Among the gases studied, ethane, cyclopropane, halothane and diethyl ether showed significantly smaller lambda values in the oxygenated blood than in deoxygenated blood, whereas SF6, acetone and N2 were little dependent on SO2. An increase in lambda was found for ethane and a decrease for halothane with increasing pH in the blood. The other gases were not significantly influenced by pH. In spite of these experimental findings, regional difference of either SO2 or pH in the lung did not exert important influence on the inert gas exchange or on the predicted VA/Q distribution. In conclusion, blood-gas partition coefficients of some inert gases are consistently altered by SO2 and pH, but their possible effects on inert gas exchange seem to be negligible.

Adult↗

Continuous distributions of ventilation and gas conductance to perfusion in the lungs.

Theoretical analysis and experimental observations were conducted to establish a method allowing to demonstrate the characteristics of distribution of ventilation (VA) as well as of diffusive conductance (G) to perfusion (Q) in the lungs. O2, CO2 and CO binding to hemoglobin molecules within the erythrocyte together with six inert gases including SF6, ethane, cyclopropane, halothane, diethyl ether and acetone, of varied solubility in blood and different diffusivity in lung tissue, were used as indicator gases. 15 patients with interstitial pneumonia of unknown etiology, placed in the supine position, were given a mixture of 21% O2 and 0.1% CO in N2 as the inspired gas and saline containing appropriate amount of the six inert gases was infused via an antecubital vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken through catheters inserted into the femoral and pulmonary artery. The concentrations of the indicator gases in the samples were measured by gas chromatography, with electrodes or with the Scholander gas analyzer. Assuming that the mass transfer efficiency of a given indicator gas at each gas exchange unit would be limited by VA/Q and G/Q ratios, the data obtained from the human subjects were analyzed in terms of a lung model having 20 units along the VA/Q and G/Q axes, respectively. The numerical analysis including the procedure of simultaneous Bohr integration for O2, CO2 and CO in a pulmonary capillary and the method of weighted least-squares combined with constrained optimization permitted the data to be transformed into a virtually continuous distribution of Q against VA/Q and G/Q axes. The numerical procedure was strictly tested using various artificial distributions of VA/Q and G/Q ratios, showing that it could characterize the distributions containing up to at least two modes on VA/Q-G/Q field with a substantial accuracy. Analytical results estimated from the patients with interstitial lung disease revealed the following features. (1) There appears to be bimodal distribution of Q along G/Q axis extending to relatively low G/Q less than 10(-3) ml(STPD)/(ml.Torr), which may limit O2 exchange between alveolar gas and capillary blood. This area of low G/Q receives 10% of total Q. (2) Severe diffusion limitation causing disequilibrium of the inert gas across the blood-gas barrier is solely observed in 2 out of 15 patients and an amount of Q associated with this phenomenon is very small (below 1%).(ABSTRACT TRUNCATED AT 400 WORDS)

Carbon Dioxide↗

Intraluminal esophageal diverticulum.

An intraluminal esophageal diverticulum (IED) is an uncommon entity defined as a double-layered mucosal pouch lying within the lumen of the esophagus. Its characteristic radiological finding is an intraluminal barium collection surrounded by a radiolucent halo. True IED, which is different from a transient radiological artifact, has not been previously reported in the international literature. This article describes the first case of true IED. Differential diagnosis between a true lesion and a transient flow artifact on barium meal is discussed.

Adult↗

[Characteristics of impaired gas exchange in patients with chronic obstructive pulmonary disease].

Eleven patients with chronic obstructive pulmonary disease (COPD), placed in a supine position, were given a mixture of 0.1% CO and 21% O2 in N2 as inspired gas and normal saline containing the six inert gases including SF6, ethane, cyclopropane, halothane, diethyl ether and acetone via the antecubital vein. After the steady state was established, the expired gas was collected and both arterial and mixed venous blood were simultaneously sampled through the catheter inserted either into the femoral or pulmonary artery. Assuming that mass transfer efficiency of a given indicator gas at each gas exchange unit would be limited by the ratio of ventilation to perfusion (VA/Q) and by that of diffusive conductance to perfusion (G/Q), the data were analyzed by means of a lung model with 20 units along the VA/Q and G/Q axes, respectively. By application of the method of weighted least-squares combined with the idea of constrained optimization, the data were transformed into a virtually continuous distribution of Q against VA/Q and G/Q axes. Analytical results revealed that: 1) patients with advanced COPD show widening of VA/Q distribution accompanied with a significant contribution of either high VA/Q (emphysematous change) or low VA/Q area (peripheral airway involvement). and 2) their Q distributions along the G/Q axis are unimodal but have an area with a relatively low G/Q, indicating a small but appreciable contribution of diffusion limitation to their hypoxemia. In conclusion, the findings consistently suggest that inhomogeneity of G/Q may partly be responsible for the impaired gas exchange in the cases of COPD.

Humans↗

[A case of infective endocarditis due to Streptococcus agalactiae].

A 60 year-old woman, who was pointed out as having hyperglycemia, was admitted to our hospital, with a two-week history of fever. Blood sugar on admission was 424 mg/dl and blood cultures yielded Streptococcus agalactiae. Systolic and diastolic heart murmurs were heard. Echocardiography showed aortic regurgitation and vegetation on the aortic valve. Penicillin-G (4 million units every 4 hr) iv and streptomycin (1 g every 12 hr) im were started. Chemotherapy was continued for 48 days. After chemotherapy, aortic valve replacement was done. We reported a very rare infective endocarditis case due to Streptococcus agalactiae.

Endocarditis, Bacterial↗

Clinical study on the hypotensive effect of diltiazem hydrochloride.

Diltiazem HCl was administered p.o. at a fixed daily dose level of 180 mg to patients with essential hypertension, and the hypotensive effect of the drug was investigated. The following results were obtained: diltiazem HCl given alone exhibited a hypotensive effect on systolic pressure in 88.9% of the patients and on diastolic pressure in 66.7% of the patients. The concurrent use of diltiazem HCl with trichlormethiazide exerted a hypotensive effect on patients who were nonresponsive to diltiazem HCl alone. As regards side effects, one patient complained of gastric fullness and one of dizziness. However, the symptoms were so mild that further continuation of diltiazem HCl therapy was possible. From the results obtained, it is concluded that diltiazem HCl can effectively be used clinically as a hypotensive drug.

Adult↗

Chemotherapeutic study on canine gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

Studies were made on the chemotherapy of gastric cancer in dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Four male Beagle dogs were given a solution of ENNG at 100 approximately 150 microgram/ml with or without 0.4% Tween 60 to drink for 5 approximately 8 months. They all developed gastric adenocarcinomas, which were confirmed by histological examination of biopsy specimens taken in months 13 approximately 32 of the experiment. After confirming the presence of gastric cancer, 1-n-hexylcarbamoyl-5-fluorouracil (HCFU), a derivative of 5-fluorouracil, was given to the dogs orally as capsules at a daily dose of 5 or 10 mg/kg body weight. One dog died from adverse effects of HCFU 12 days after the beginning of chemotherapy. The other 3 dogs were treated with CHFU for 82 approximately 424 days. In these dogs, the tumor size, measured by X-ray examination, increased during chemotherapy. On autopsy, the tumors in the stomach were found to be restricted to the antrum, and metastases of the gastric adenocarcinomas to the regional lymph nodes and/or liver were found in 2 dogs. No degenerative changes of tumor cells were found in the stomach or metastasized organs, except for necrosis of cells in a perigastric regional lymph node of the dog. The value of using canine gastric cancer in studies on chemotherapy is discussed.

Adenocarcinoma↗

A study on vectorcardiographic criteria for evaluating right ventricular hypertrophy in chronic obstructive pulmonary disease.

Vectorcardiographic analysis was mainly made on the basis of hemodynamic findings through right heart catheterization in COPD. From the results obtained in the present study, the authors proposed the following quantitative VCG criteria as a mean for clinical recognition of right ventricular overload in patients with COPD. (I) Individual parameters of the criteria are: i) The QRS loop; (a) P/A (posterior force/anterior force) greater than or equal to 2.8 (b) R/L (rightward force/leftward force) greater than or equal to 0.6 (c) P/6 (posterior force/leftward force) greater than or equal to 1.8 ii) The P loop; Ap/Pp (anterior force/posterior force) greater than or equal to 1.8 (II) Criteria i) "RVH (right ventricular hypertrophy)" should satisfy more than 3 of the above individual parameters. ii) "RVH suspected" should satisfy 1 or 2 of them. iii) "RVH negative" should not satisfy any of them. The recognition rate for RVH by the present VCG criteria was higher than the conventional ECG criteria and there was good correspondence with autopsy findings.

Adult↗