As previously described in report 1, metachromatic substance was found in different degrees in artery and vein walls. The changes in metachromatic substance (quantitative and qualitative) were studied by electrophoresis on filter paper. The acid polysaccharide fractions were extracted from the blood vessel wall by alkali treatment or enzyme treatment, and showed red metachromasia on toluidine blue staining at the site corresponding with the position of "hi" acid and "cho" sulfate samples on electrophoresis, the elution of each spot showed a positive glucosamine reaction, and was negative to B. P. B. and ninhydrin reactions. For these reasons, it is probable that these spots consist of "hi" acid and "cho" sulfate. The "cho" sulfate fraction was hydrolysed by chondromucinase, but the "hi" acid fraction was not hydrolysed. The "cho" sulfate fraction and the "hi" acid fraction were hydrolysed by hyaluronidase. Thus, it is probable that the "cho" sulfate fraction contains chiefly "cho" sulfate, and the "hi" acid fraction contains chiefly "hi" acid. Arteries and veins contain a small amount of the "hi" acid fraction and a large amount of the "cho" sulfate fraction.

View full abstract

Study was made on the frequency distribution and the absolute intensity of the chest wall vibration caused by the mechanical action of the heart in order to establish a physical basis for standardization of phonocardiograph and calibration of heart sounds and murmurs. Thereafter, the available results were obtained.

View full abstract

Our recent results obtained by intracardiac phonocardiography are reviewed. As one of the factors in production of murmurs abnormal turbulence within the heart and great vessels must be taken into account. As a morphological proof of this turbulence the so-called jet lesion can be considered. Some examples of normal humans, experimental dogs, human pathological states and that of the congenital heart diseases are demonstrated. The cases discussed on this occasion are those which presented various problems and interpretations are attempted based mainly on intracardiac phonocardiograms.

View full abstract

Haldane and Barcroft's postulate in 1920 (Lancet) that "anoxemia not only stops the machine, but wrecks the machinery", leads to the concept that the enzyme activities of tissues should be damaged in anoxemia. There are reports that activities of enzymes which metabolize substrates located near the entrance to the TCA cycle, namely pyruvate and citrate, are depressed due to hypoxia, especially with studies on myocardial tissues (Kimura, S., from our department; Jap. Circulation J. 21 : 376, 1957). However, information on tissues of other organs is relatively lacking. Also, comparative studies concerning the influence of hypoxemia, caused by low percentage oxygen respiration under normal atmospheric pressure, on the above mentioned enzyme activities of the heart and other organs are lacking. Furthermore, there is a question unclarified, whether acute hypoxia can sometimes increase respiratory enzyme activity, and also the relation between the changes in the enzyme activity and the degree of hypoxia is left unclarified.The present study was undertaken to elucidate the above points, with experiments on tissues of the heart, brain, liver and kidney.Materials and Methods Male albino rats, weighing about 150 grams, were placed in gas mixtures containing 10, 5 or 3±0.2% O₂ with adequate ventilation at normal atmospheric pressure for several minutes to 5 hours and decapitated.Estimations of dehydrogenase activities were made on tissues homogenates of myocardium, cerebral cortex, liver and kidney, by the Thunberg technique. Sodium salts of lactic, pyruvic, citric and succinic acids were used as substrates. The decolorizing time of methylene blue was used for statistical analyses, but the ratio-methylene blue reduced (γ)/decolorizing time (minutes)- was considered an indicator of methylene blue reducing, i.e. substrate oxidizing, capacity of tissue homogenates, and used for the calculation of percentage changes.The endogenous respirations of homogenates of myocardium and cerebral cortex, were determined by the Lemley and Meneely's method. Also, the Qo₂ of homogenates with pyruvate, citrate or succinate as substrate were obtained.Results Obtained 1. Normal controls The oxidizing capacities of tissue homogenates when pyruvate, citrate or succinate is used as substrate are-myocardium>kidney>liver>brain-the brain being especially weak. Also, with these substrates, the Qo₂ of myocardial homogenates are larger than that of the brain. The addition of citrate had little or no effect on the oxidizing capacity and Qo₂ of brain homogenates. It was felt, as reported by others, that the TCA cycle activity was weak in the brain tissue.2. Effects of various degrees of hypoxia a) Relatively mild hypoxia (10 % O₂) for 2 hours : The homogenates of myocardium and brain showed no significant change in their oxidizing capacity, but significant increases were observed with liver and kidney homogenates. Especially with the liver, compared to control values, the endogenous oxidizing capacity was increased by +47 % (P<0.01), and with lactate, pyruvate or citrate as substrate, respective increases of +39 % (P<0.01), +23 % (P<0.05) and +34 % (P<0.02) were noted.It was concluded that relatively mild hypoxia of this degree and duration, could cause increases in the oxidizing capacities of liver and kidney tissues, while those of the myocardium and brain were maintained.b) Moderate hypoxia (5 % O₂) for 10 minutes to 5 hours : The oxidizing capacity of tissue homogenates showed no significant change after 10 minutes of 5 % O₂ respiration. One hour of hypoxia caused decreases in the oxidizing capacities of myocardial homogenates, only when pyruvate (-22%, P<0.01) or citrate (-33%, P<0.01) were used as substrates.After 2 hours of hypoxia, significant decreases were found in all tissues studied. [the rest omitted]

View full abstract

While the subject of hypoxia associated with liver diseases is drawing an increasing interest of medical investigators these days, no large body of informations is yet available on the effect of hypoxia on the blood circulation through, and gas metabolism in, the liver. Particularly, such informations are practically nil in man. The author attempted to evaluate the role of the liver in the organism's regulatory response to an induced hypoxemia in a variety of conditions e.g., in the convalescent stage of hepatitis, in chronic hepatitis or cirrhosis of the liver and pulmonary tuberculosis.Methods and Subjects : Each patient was subjected to the venous catheterization; arterial blood was obtained from the femoral artery and the venous blood was drawn through the catheter. The hepatic blood flow was estimated by the B.S.P. method of Bradley and, at the same time, various parameters of the blood circulation and gas metabolism in the liver were measured, e.g., hepatic vein wedge pressure, hepatic-portal vascular resistance, splanchnic O₂ extraction and splanchnic O₂ consumption. After a course of measurment during a resting state was over and another course of measurement (of the hepatic blood circulation and hepatic gas metabolism) was made during the 15th-20th minute interval of the hypoxemia test, which was induced by Levy's method with 10% O₂ gas. The cardiac output was measured by direct the Fick's method in a resting state and at the 20th minute of the hypoxemia test.Subjects examined were 28 cases in total and they consisted of 5 groups.Group I : normal subjects (6 cases)Group II : patients with pulmonary tuberculosis who were scheduled to be operated on for surgical treatment (10 cases). This group consisted of 2 subgroups; subgroup A represents those who gave no abnormal liver function tests, and subgroup B represented those who gave abnormal liver function tests.Group III : convalescent patients with acute hepatitis (4 cases). This group covered the stage of the disease between the 37th and 114th day after the onset of the disease; liver function tests and liver biopsy findings were nearly normal in all cases.Group IV : Chronic hepatitis (4 cases). This group covered the stage of the disease between the 4th and 21st month since the onset of acute hepatitis; liver biopsy revealed the degenerasion of hepatic cells, round cell infiltration and slight fibrosis.Group V : Cirrhosis of the liver (4 cases). This group represented those in whom signs of hepatic insufficiency (ascites, jaundice, etc., ) have subsided to a considerable extent.Results : The observed effect of hypoxemia was as follows.(1) Systemic circulation and gas metabolism : The observed response was nearly the same in all groups with regard to the artery blood pressure, cardiac output, arterial blood O₂ contents and total O₂ consumption of the body. The artery blood pressure was reduced by about 15 % and the cardiac output was either unchanged or slightly reduced : the arterial blood O₂ contents were reduced by 30-40 % and the total O₂ consumption was slightly reduced (by about 20%).(2) Hepatic vein wedge pressure : This was measured in 2 normal subjects and 7 cases with liver diseases (acute hepatitis in convalescence and chronic hepatitis). It was increased by 18 % in normal subjects and increased by 28% in patients with liver disease.(3) Estimated hepatic bloood flow : It was increased markedly in Group I, by +68% ; it was also increased in Group II, by +31%; within this group the pressure was different between the two subgroups, the increase being marked in subgroup A (+50%) but nil in subgroup B. No increase was found in groups III, IV and V. Furthermore, the blood flow was decreased in groups III (-26%) and V (-30%). [the rest omitted]

View full abstract

It is established that hypoxia causes the elevation of the pulmonary arterial pressure. However, there is no definite concept sufficient to account for the mechanism of the elevation of the pressure; some investigators regard increase in amount of the cardiac output as its main reason, and the others emphasize the changes in constriction of the pulmonary artery, resulted probably from hypoxia.A series of studies on patients with pulmonary tuberculosis was carried out in an attempt to determine the effects of hypoxia in a moderate extent which may disturb the cardiopulmonary function of the patients. A possible mechanism for the elevation of the pulmonary arterial pressure will be discussed in this paper.Materials and Method A total of 25 patients with pulmonary tuberculosis were subjected to this study. Pneumonectomy was done in two cases and the remaining 23 cases were divided into the following three groups on the basis of the classification presented by American National Tuberculosis Association (1950); five being minimal cases, 11 moderately advanced cases and 6 far advanced cases (Table 6).The following measurements were made on all patients in both ambient air breathing and low oxygen breasing, 12 to 15% of O₂ in N₂ for 8 to 20 minutes : pulmonary wedge pressure by the technique of the right heart catheterization; oxygen and carbon-dioxide content of both blood and expired gas using Van Slyke-Neill apparatus and Rokenshiki gas analyzer, respectively; oxygen saturation of the arterial and venous blood; cardiac output by the direct Fick method. Spirometry using Collins' apparatus was also made on all cases, representing its data in percentages of predicted values calculated by Funazu's formula.Results The elevation of the pulmonary arterial pressure due to hypoxia was found in 22 cases of all 23.The pulmonary arterial pressure in the ambient air breathing was below 20 mmHg in all cases of the minimal group and it was over 20 mmHg in only two of the moderately advanced group. The average value of the pressure was lower in the former group than in the latter. The pulmonary arterial pressure in both far advanced and pneumonectomized groups was over 20 mmHg with an exception of one case, their average being over 20 mmHg. Degree and rate of elevation of the mean pulmonary arterial pressure due to the hypoxia were reduced in average in the order of minimal, moderately advanced, far advanced and pneumonectomized groups.The pulmonary arterial pressure of the patients with minimal tuberculosis showed the elevation, which appeared immediately after exposure to the hypoxia, reached the highest value after 3 to 5 minutes and continued as long as the patients were in the hypoxia. The pressure returned to the original level just after cessation of the hypoxia. The elevation was much more marked in the systolic pressure than in the diastolic.The pressure of the pulmonary artery in the hypoxic condition in several cases of the moderately advanced group showed a temporary elevation, reaching the highest value in 5 to 10 minutes, and then its gradual falling. The pressure did not return immediately after cessation of the hypoxia, but did within one hour, to the original value. Narrowing of the pulse pressure was observed in these cases in the terminal stage of the hypoxic condition. The elevation of the pressure in two cases was more intensive in the diastolic than in the systolic. The cases of the far advanced group showed the similar response of the pressure to the hypoxia to the former group was noticed, accompanied with various patterns of fluctuations of the pressure.The shape of the pulmonary arterial pressure curve showed the reduction of elastic elevation in the hypoxia and returned to the former shape after cessaiton of the hypoxia (Fig 6). [the rest omitted]

View full abstract

While there are many reports as to the elevation of the pulmonary artery blood pressure during an induced hypoxemia, quantitative relationships between the change in respiration and that in the pulmonary circulation is not yet fully clarified in cases with different diseases. Many studies have been done in this department since 1954 by using the method of induced hypoxemia combined with the cardiac and venous catheterization on the blood circulation through various organs, such as the heart, brain, liver and kidneys, and the response to the induced hypoxemia has been studied in a variety of conditions. This paper aims to describe the author's study on the effect of induced hypoxemia on the pulmonary circulation and also his consideration on the relation between the pulmonary and the systemic circulation in normal subjects, patients with pulmonary tuberculosis and cardiac patients.Methods and Subjects Each subject was examined by the cardiac and venous catheterization method under the resting and fasting condition; with the catheter tip in a main pulmonary artery, the subject was made to breathe from a sourve of 10% O₂ gas with half mask and Douglas bag for a period of 20 minutes.The pulmonary artery pressure was recorded by an electro-manometer at intervals of 5 minutes; the blood gas was measured on the mixed venous blood and arterial blood at the same time. The subjects examined 23 cases in total, including 5 normal subjects (Group A), 12 patients with pulmonary tuberculosis (Group B), 6 cases with cardiac diseases (Group C) consisting of 5 cases with mitral stenosis and one case of ventricular septal defect.Results(1) Respiration and O₂ consumption : The rate of respiration and minute ventilation volume were increased in all groups, i.e., hyperventilation, and there was no significant difference among the groups. The rate of O₂ consumption (per minute) was decreased in all groups; it was decreased more markedly in pulmonary and cardiac patients than in normal subjects, the difference being statistically significant.(2) Blood gas : The O₂ contents were markedly reduced in the arterial blood and mixed venous blood. The recorded arterial blood O₂ saturations were; normal subjects (62.8%), pulmonary tuberculosis (63.0%) and cardiac disease (59.8%). The mixed venous blood O₂ saturations were : normal sebjects (42.6%), pulmonary tuberculosis (43.5%) and cardiac disease (42.5%). There was no significant difference among the groups. The CO₂ contents of the arterial blood and mixed venous blood were slightly reduced in all groups, the decrease being more marked in the group of pulmonary tuberculosis than in other groups.(3) Systemic circulation : The mean brachial artery blood pressure was lowered in all cases, but relatively more markedly in pulmonary (10%) and cardiac patients (18.7%) than in normal subjects (4.4%).(4) Pulmonary Circulation : The mean pulmonary artery pressure was elevated in all groups; the degree of such elevation was obviously different from group to group and in ascending order as follows : normal subjects, pulmonary patients, cardiac patients. The elevation of the mean pulmonary artery pressure value per 10% decrease in oxygen saturation of the systemic arterial blood amounted to 1.3, 1.9, 3.3 mmHg respectively. The pulmonary "capillary" pressure was not altered in all groups.While the pulmonary blood flow was reduced in all groups, and it was then reduced more markedly in pulmonary (30.1%) and cardiac patients (29.8%) than in normal subjects (10%). The pulmonary vascular resistance was therefore increased in all groups and it was increased more markedly in pulmonary and cardiac cases than in normal subjects.The pressure work of the right ventricle was increased markedly (22 %) in normal subjects, but slightly (13%) in cardiac patients. [the rest omitted]

View full abstract

It iswell known that pulmonary resection is the most reasonable surgical therapy for pulmonary tuberculosis. Pulmonary resec- tion, however, causes, on the other hand, some decrease of diffusing area and of vascular bed. Accordingly studies on its effects upon the cardiopulmonary function are clinically important.Many authors have reported about its effects on pulmonary function, and their results are roughly unanimous in that the degree of pulmonary insufficiency is proportional to the volume of resected lung parenchyma while it can be remarkably various depending on the post-operative complications even in the group in which the volume of resected parenchyma is the same. Rather few reports, however, were found on the effects of pulmonary resection upon pulmonary circulation, and in these reports the degree of elevation of pulmonary arterial pressure is not proportional to the volume of the resected pulmonary parenchyma. This shows that pulmonary circulation has a large compensatory capacity, and suggests that these are also other important factors for the elevation of pulmonary arterial pressure besides the decrease of vascular bed. Concerning pulmonary resection, detailed studies have not yet been reported on the correlation between pulmonary function and pulmonary circulation and on the physiological adaptation of right ventricle against a load on pulmonary vascular bed. This paper reports the author's results upon these points.Methods The methods used for the venous catheterization etc. were the same as those in the first report of the present studies. The subjects were 10 patients under various kinds of pulmonary resection, and they were examined eleven times. Group I consists of 3 patients under partial resection, group II of 4 patients under lobectomy, group III of 1 patient under lobectomy followed by partial resection (this patient is also included in group II) and group IV of 3 patients under pneumonectomy.Results Lung volume and ventilatory function : The greater the volume of resected pulmonary parenchyma was, the more remarkable was the decrease in VC and MBC. But the former was not always parallel to the degree of the latter. And compared within the same group, the decrease in VC was more remarkable in patients with pleural callosity or with kyphoscoliosis etc. caused by operation. In 2 patients of group IV (No. 240, 241) the elevation of spirogram to the inspiratory level was noted during the measurment of MBC.Minute ventilation, alveolar ventilation and alveolar ventilation ratio : These were normal or only slightly increased in group I and II respectively, and the increase in alveolar ventilation was more remarkable than that of minute ventilation, so that the increase in alveolar ventilation ratio was noted. In group III these were normal. But in spite of the increase in minute ventilation, alveolar ventilation was normal in group IV, and alveolar ventilation ratio stood at lower limit of normal. In general, positive correlation was found between alveolar ventilation ratio and %VC (Fig. 1).Arterial O₂ saturation was nearly at lower limit of normal in group I and II, while it was clearly lower than normal in group IV, and the largest decrease was found in group III. At the same time negative correlation was noted between arterial O₂ tension and A-a O₂ tension gradient. In case %VC decreased under 40% of normal, %VC showed positive correlation with alveolar O₂ tension, while negative with arterial CO₂ tension (Fig. 3).Pulmonary circulation : Pulmonary blood flow was normal in all groups. Right auricular pressure and right ventricular enddiastolic pressure were clearly elevated in 3 patients. Pulmonary arterial pressure was elevated evidently in some patients in group I, while it was normal in one patient in graup IV. [the rest omitted]

View full abstract

In studies of electrolyte metabolism, there are relatively many reports on in vitro and animal experiments, but hardly no reports are seen of clinical studies on the effect of acute induced hypoxemia on electrolyte metabolism. Above all, no reports are found on a clinical patho-physiological study of the effect of acute induced hypoxemia on electrolyte metabolism (Na⁺, K⁺) of the liver by means of hepatic venous catheterization.Therefore, in order to make clear the influence of acute induced hypoxemia upon the electrolyte metabolism in the liver, the author measured the electrolytes(Na⁺, K⁺) of the systemic arterial and hepatic venous plasma of healthy subjects and those with liver diseases before and during low oxygen inhalation.Methods and Materials.The inhalation of 10% O₂ for 20 minutes was accomplished according to the original Levy's method during a retsing and fasting state.The subjects examined are : Group 1 : Healthy, …9 cases.Group 2 : Light or moderate pulmonary tuberculosis, …14 cases.Group 3 : Cardiovascular diseases, …12 caess.(Essential hypertension 11 cases, and Compensated mitral stenosis 1 case.)Group 4 : Liver diseases, …10 cases.(Acute hepatitis in the convalescent stage 4 cases, chronic hepatitis 4 cases, Banti's syndrome 1 case and hepatic cirrhosis 1 case.)In these 45 cases, samples of systemic arterial blood were taken before and during acute induced hypoxemia, above mentioned.The hepatic venous catheterization was performed in the following 18 cases and samples of the systemic arterial blood and the hepatic venous blood were taken before and dnring the acute incuced hypoxemia.A. Control Group (9 cases) : Healthy…3 cases, Arteriosclerosis…1 case, Gastritis…1 case, Pulmonary tuberculosis, …3 cases, Compensated mitral stenosis, …1 case, B. Group with liver diseases. (9 cases) : Acute hepatitis in the convalescent stage, …4 cases, Chronic hepatitis, …3 cases, Banti's syndrome…1 case, Hepatic cirrhosis…1 case.The measurement of electrolytes (Na⁺, K⁺) was accomplished by the S. Shibata's method by utilizing a flamephotometer.Furthermore, the blood gas (Van Slyke method), glucose (Somogyi method), lacate (Hydroxybiphenyl-hydrazine method), pyruvate (Dinitrophenyl-hydrazine method) and the estimated hepatic blood flow (E.H.B.F., by the Bradly method) were measured.Results and Conclusions.I. SODIUM AND POTASSIUM LEVELS OF THE SYSTEMIC ARTEIRAL PLASMA.1) In the resting and fasting state, the sodium level is elevated statistically insignificantly in groups 2 and 3 as compared with the healthy group, and statistically signiffcantly (p<0.02) in group 4.The potassium level is lowered significantly (p<0.05) in group 4.2) The effect of induced hypoxemia : The level of sodium revealed a significant increase (p<0.01) after 15 to 20 minutes. The potassium level revealed a significant decrease (p<0.01) after 5 minutes of hypoxia, an earlier change than the sodium. Further decrease of the potassium level was seen after 15 and 20 minutes.3)When the effect of the oxygen want on the level of arterial plasma sodium and potassium was compared between the healthy and each diseased group, the level of potassium distinctly decreased in each group but the level of sodium increased clearly only in the liver diseased group.4) Thus, the effects of induced hypoxemia is an increase of the level of arterial plasma sodium and a decrease of the level of potassium, and these changes are similar to those introduced by the administration of adrenocortical hormone or the subcutaneous injection of adrenaline. The author makes the supposition from these results, that the stress from the acute induced hypoxemia is related with the pituitary-adrenocortical system.II. [the rest omitted]

View full abstract