Chapter I. The method of the measurement of vanous return A new method was advanced to measure the rate of venous return by a dilution technique employing the electric conductivity method. The validity of this method, as applied to the venous system, was confirmed in carefully controlled model-experiments and animal experiments. This study revealed that the measurement of venous flow by dilution technique was valid, when the electrode was placed at least 4 cm downstream to the junction of any main tributary and the caval vein. The observed venous return and the relative contribution of individual tributaries (regional distribution) in dogs weighing about 10 kg were : total venous return 1.41l/min ; superior caval vein 36.7%, inferior caval vein 63.3%, hepatic vein 36%, renal veins 16.7%, lower limbs and pelvic viscera 10.6%, taking the total venous return as 100. The author discussed the advantage and disadvantage of this method in actual measurement of the venous flow.Chapter II. Regulation of the venous return and its regional distribution ; the role of the carotid sinus reflex As an approach to the problem of the nervous control of venous return, the author studied the effect of carotid sinus reflex on the venous return in dogs ; the maneuvres employed were : the occlusion of the common, and internal and external carotid artery, and the carotid sinus denervation ; the effect of such maneuvres on the venous return and relative venous flow from different tributaries (regional distribution) was studied. The venous blood flow was measured by a dilution technique employing the electric conductivity method, such as described in Chapter I. The common carotid artery occlusion caused the venous return to increase; the carotid sinus denervation changed the regional distribution of the venous return. It became clear that the carotid sinus reflex does not uniformly affect the entire blood vessels of the body, but causes the distribution of blood flow to change. These observations support the veiw that the purpose of the circulatory adjustment, including the re-distribution of blood flow to different parts of the body.Chapter III. The role of the carotid sinus reflex in the hemodynamic response (venous flow) to the circulatory crisis produced by acute bleeding or induced anoxaemia In Chapter II it was found that the carotid sinus reflex was capable of modifying venous return and its regional distribution. In this Chapter the author sought answer to the question, ""what happens to the venous return in a circulatory crisis and what role does the carotid sinus reflex play under such circumstances?"" For this purpose the author performed two experiments; one, that of an acute bleeding and, other, that of induced anoxaemia (inhalation of low O₂ gas). Following acute bleeding there was marked increase in the hepatic venous flow indicating the ""driving out"" of the splanchnic blood depot; such increase in the hepatic venous flow in response to an acute bleeding was not seen after the destruction of carotid sinus nerve activity. The induced anoxaemia caused the total venous return to increase; increase was relatively marked in the superior caval venous flow, with the result that the weight of the superior caval venous flow to the total venous return was increased. For such change in the venous return partly responsible is the carotid chemoreceptor mechanism. However, in the case of the organism's response to the induced anoxaemia the effect of carotid sinus denervation was relatively insignificant as compared with the effect of the same maneuvre on the organism's response to acute bleeding.

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In 42 patients with cardiac decompensation, total venous return and venous flow from the several kinds of organs and its bodily distribution in respective regions (regional distribution) were measured by the electric conductivity method already described in the previous report and the correlations of the obtained values to the circulatory hemodynamic datas were discussed. In the patients with cardiac decompensation, regional distribution of venous return was different from that of control cases in cormal cardiovascular condition. That is, comparing with the proportional decrease of total venous return to the grade of cardiac decompensation, the decrease of venous flow from all parts of body was observed, among which, especially, the decrease of venous flow from the renal region, i.e. renal venous return, was most obvious. On the contrary, venous flow from the cranial region also a little decreased in absolute value, but inversely relative ratio of cranial venous flow to the total venous return increased, although marked decrease of cardiac output was seen. From this fact, it may be suggested that in human body, regulating mechanism of blood flow is playing a role in the maintenance of blood supply to the important part of body, such as brain.

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A fish embryo was used for the micro-determination of drugs which have the action on heart. After the treatment of Hyaluronidase, the stable conditions for the permeability were obtained. Under these conditions, drugs can be applied without surgical injuries or complicated techniques.

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The ""GO"" (gradual occlusion) of the anterior descending ramus of the left coronary artery was effected at the origin of this artery, utilizing the growth of a localized dicetyl-phosphate granuloma in 27 dogs, and pertinent features of such ""GO"" dogs were analysed in comparison with the characteristics of 9 normal dogs and 6 dogs with acute myocardial infarction produced by the ligation of the anterior descending ramus.

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Thoracoplasty is now performed not so frequently as before on account of the popularity of pulmonary resection, but it is still performed widely for the patients with far advanced pulmonary lesions. Therefore there are a number of studies on its effect on the pulmonary function, and detailed studies with spirometry, bronchospirometry and blood gas analysis etc. have been reported about it. On the other hand there are few reports on the pulmonary circulation, and I can not find in litrature comprehansive studies in which venous catheterization and pulmonary function tests are performed simultaneously. This paper reports the present author's results concerning these points.Methods : The methods used for the venous catheterization etc. were similar to those in the first report of the present series. The subjects were 13 patients under thoracoplasty (Group I), and 3 patients under both thoracoplasty and other types of collapse therapy (Group II). Group I was then divided into 3 sub-groups according to the degree of collapse. Namely, the patients with slight lung-collapse formed group a, those with moderate collapse group b, and those with high collapse group c.Results : (1) Group 1 : The decrease in VC was fairly marked, but the decrease in MBC remained relatively slight, and neither of them showed any correlation with the degree of collapse. Minute ventilation tended to increase, especially in group c. Alveolar ventilation was normal, and no correlation was found with the degree of collapse. Alveolar ventilation ratio was the more decreased, the higher the degree of collapse. And the latter showed roughly a positive correlation with % VC.Arterial O₂ saturation dropped in general, especially in group c. While arterial CO₂ content was normal. Arterial O₂ tension dropped markedly, and A-a O₂ tension gradient showed a great increase simultaneously, there being a negative correlation between them. Upon each one patient out of the three groups muscular exercise was imposed, and after that arterial O₂ saturation was elevated in all of the three.Cardiac index was normal in average, showing a wide range of variety case by case. And there was not found any correlation between the degree of collapse and the change in cardiac index. However, the increase or decrease in cardiac index was correlated with the change in O₂ consumption and in patients with decreased cardiac output there was found an increase in vascular resistance and in arterio-venous O₂ difference. In three patients muscular exercise was imposed, and cardiac index increased.Right auricular pressure was normal in average, but in a few patients it was found to be clearly elevated or lowered. Right ventricular pressure was normal in general. Pulmonary arterial pressure tended to rise both in diastole and in mean. Its correlation was not found with factors concerning the elevation of pulmonary arterial pressure reported in the previous paper, while it showed only some tendency of correlation with the increase in % VC. Among 3 patients with moscular exercise, the elevation of pulmonary arterial pressure was the most signficant in the patient who gave a remarkable increase in the cardiac output after exercise. Two patients of the three showing a clear elevation of wedge pressure belonged to group c.Vascular resistance was increased remarkably both in pulmonary arteriolar and in pulmonary vascular and the increase in the former was remarkable in patients with far advanced lesions in the non-collapsed lung. The work of right ventricle against pressure was normal.In the most patients with low arterial O₂ tension there was found a flat T wave electrocardiographically.(II) Comparison of the results before and after thoracoplasty in the same patients : The decrease in VC was slight. [the rest omitted]

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Krogh and Roughton have estimated the pulmonary diffusing capacity using the carbonmonooxide technique. Recently Rilely et al designed a new procedure to estimate both pulmonary diffusing capacity and venous admixture. Mc Clement et al, Anderson et al have reported, using Riley's method, studies on various pulmonary diseases including tuberculosis.Estimation of both pulmonary diffusing capacity and venous admixture of patients with pulmonary tuberculosis, with the method of Riley et al, was made by the author in an attempt to answer their significance relating to the pulmonaty circulatory and ventilatory functions.Materials and Method : 15 patients with pulmonary tuberculosis, three being minimal, seven moderately advanced, three far advanced and two pneumonectomized cases, were studied by the right heart catheterization technique in ambient air breathing 12 to 15 percent oxygen gas mixture. Expired gas, arterial blood, and mixed venous blood were taken from the patients in both ambient air and low oxygen breathing. Blood gas tension was measured by the method of Riley et al, using the Roughton-Scholander's syringe. pH of the blood was determined by the method of Singer-Hastings. Alveolar gas tension was calculated from the alveolar equation ; effective alveolar carbon-dioxide tension being assumed to be equal to carbon-dioxide tension of the arterial blood. Respiratory dead space was calculated by the Bohr's equation.Results Three minimal, four moderately advanced, and one pneumonectomized cases showed the normal diffusing capacity, but other cases, depressed diffusing capacity. The diffusing capacity, in average, of the minimal cases fell into a normal range, and that of the moderately advanced cases was at the lower level of a normal range, and that of the far advanced was surely under this range. Venous admixture was normal in two minimal and one pneumonectomized cases but was increased in the order cases. The venous admixture in average was increased in the other of the minimal, moderately advanced, and far advanced cases. Among two pneumonectomized cases, one showed normal venous admixture and depressed diffusing capacity, and the other increased venous admixture and normal diffusing capacity. Respiratory dead space was found to be over normal in one minimal, two moderately advanced, and three far advenced cases. It was apparently increased, in average, in far advanced cases. The respiratory dead apace ratio was negatively related to the carbon-dioxide tension of the arterial blood.Alveolar-arterial oxygen tension gradient (A-a gradient) was within normal limit in one minimal case; but was over normal in all other cases. Its average values were increased in the order of the minimal, moderately advanced, and far advanced cases.So far as the high level of oxygenation of the arterial blood was concerned, the A-a gradient was much closely related to the venous admixture and that in the low level of oxygenation was related to the diffusing capacity. When the A-a gradient was divided into the diffusion gradient and the venous admixture gradient, in the high level of oxygenation a very intimate correlation between venous admixture gradient was demonstrated, and in the low level of oxygenation, a similar correlation between diffusing capacity and diffusion gradient was found.No significant correlation was noted among diffusing capacity, venous admixture and respiratory dead space, or between diffusing capacity and oxygen removal. On the contrary, a positive correlation between vital capacity, percent of predicated, and a negative correlation between vital capacity, percent of predicted, and respiratory dead space were found.No correlation between vital capacity, percent of predicted, and venous admixture was found.Discussion and Summary In fifteen patients with pulmonary tuberculosis, disturbance of the pulmonary alveolar gas exchange was studied by the method of Riley et al. The diffusing capacity in average was decreased in th

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(II) Experimental Myocarditis The exprimental study of allergic myocarditis has been made by many scholars since olden times. But it was very difficult that allergic changes were produced in the disirable organ freely and locally. As the mechanism of allergy was made clear by Professor Maekawa's allergy theory and by a series of experiments on allergy in his laboratory, allergic inflamation has been able to be caused freely in the heart. Already a few reports on the relation between electrocardiographic changes in allergic myocarditis and its histological changes have been described. The reports chiefly stated that, in spite of remarkable histological changes, the electrocardiographic changes were very slight and the mutual-relationship was not clear. F or the purpose of knowing whether the electrocardisgraphic changes were caused by the myocarditis or not, the course of the disease was investigated with the limb-lead electracardiogram; moreover, to examine them in detail, the chest lead electrocardiogram with photographic method that was already reported was taken. Thus the relation between the histological change and the electrocardiographic change was studied.Method : 1) Antigens : By means of Kitasawa's method, cephalin and lecithin were extracted from ox myocardium. The white of an egg (2 cc/kg) which was diluted 50 % by physiological salt solution, or ox serum (2 cc/kg) were added to cephalin (2 mg/a rabbit) or lecithin (8.5 mg/a rabbit) and they were mixed fully. After they were let alone a room for an hour they were used.2) Rabbits were sensitized by intravenous injection of the above mentioned antigens for 3 days (once a day) and were reinjected by the same antigen for 3 days (once a day) 3 weeks later.At the 7th day after reinjection, rabbits were killed.3) Throughout this experiment, all rabbits were observed electrocardiographically and histological surveys were compared with electrocardiographic findings.4) Some rabbits were killed halfway and histological surveys were compared with electrocardiographic findings.Results and Conclusion : 1) When the substance, which a mixture of 50 % raw white physiological salt solution with ox cephalin or lecithin (the antigen) was used, the histological changes in heart were generally interstitial, sligth perivascular infiltration and more remarkable in the right ventricle than in the left ventricle.When the mixture of ox serum with cephalin or lecithin, was used : chiefly a remarkable perivascular myocarditis; moreover, interstitial myocarditis and endocarditis were found.In either case, the longer the time after reinjection, passes by the more marked histological cnanges were found.But the others before reinjection and after sensitization showed slight changes. When lecthin was used, no matter what the protein was, the histological changes in their heart were much slighter than in that case of cephalin.2) Generally, the electrocardiographic changes were weaker relative to the histological changes.When the histolofical changes extended to the pericardium, electrocardiographic findings were marked. Alterations of ST segment and T wave (monophasic ST, T) were registered both in the limb lead and in the chest lead.In other cases, in general, their findings were the elevation or depression of ST segment and increased, decreased, low or inverted T, etc.3) The relationship was as follows between electrocardiograms of rabbits and their histological findings of their heart.Namely, in 4 cases which were destroyed pericardium and myocardium among 19 cases of definite histological changes, the elevation of ST segment in lead I and lead II, the depression of Segmen in lead III, and the monophasic STCF₃, CF₄ segment and TCF₃, CF₄ wave in the chest lead were noted. They showed just the same electrocardiographic changes that were noted in man. [the rest omitted]

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In order to investigate the pathological physiology in patients with neurocircuratory asthenia (abbreviated as NCA), with special reference to metabolism, respiratory Quotient in the basal metabolic state (abbreviated as basal R. Q.) was measured in 106 cases of NCA and allied diseases. (Allied disease means atypical NCA which has only 2 or 3 out of 4 cardinal systoms of NCA.)Method The expired air, collected by the face mask and the Douglas' bag in the basal metabolic state, was analysed by a gas analyser of the Japan Labour Research Institute (Roken) type-a modified Haldana type analyser.Results 1) Under almost constant conditions, the basal R.Q. of an individual is kept almost constant for several days. Therefore, it can be used as an indicator of the individual's metabolic state.2) Influence of the food composition upon the basal R.Q. lasts more than twelve hours after eating. It is suggested, therefore, that the basal R.Q., as an indicator of an individual's metabolic state, should be measured after having a diet of constant compositions. The basal R.Q. in this article was measured 12 to 15 hours after giving the regular hospital diet.3) The basal R.Q. in patients with NCA and allied disease showed no significant difference by age or sex. The type of NCA had no significant influence on it, as well.4) The mean value of the basal R. Q. s in NCA and allied disease was 0.848. This value was lower than that in patients with heart disease or hypertension, while it was similar to that in patients with chronic nephritis or diabetes mellitus.5) The relation between the basal metabolic rate and the basal R.Q. differs according to the kind of disease.6) The mean value of the basal R.Q. in NCA and allied disease was high in patients complaining of dyspnea (0.881) and stiffness of the shoulder or neck (0.872), while it was low in patients complaining of general malaise (0.796) and fatiguability (0.812).7) The mean value of the basal R.Q. in 37 patients with NCA and allied diseases showing favourable clinical course generally increased from 0.856 to 0.921 as the symptoms improved. Especially among 8 patients with the basal R.Q. below 0.70 at the time of admission, all but one showed an increase in the basal R.Q. by the time of discharge.On the contrary, 19 patients showing no favourable clinical course revealed a decrease in the mean value of the basal R.Q. from 0.859 to 0.837.8) The group of the patients with the basal R.Q. below 0.80 indicate a delayed return to fasting blood sugar level in the glucose tolerance curve.9) In the four-hour epinephrine test in the patients with NCA and allied disease, the basal R.Q. showed no significant difference between the group responding normally and that with decreased response.10) In the eight-hour intravenous ACTH test, the mean value of the basal R.Q. was low in the group of the patients with poor responce of eosinophiles.11) The mean value of the bassal R.Q. in patients with the normal serum cholesterol level (both total and ester form) was 0.843, while the patients with the above or below normal serum cholesterol level showed the mean value of the basal R.Q. above 0.843.12) The patients with the high basal R.Q. responded to the three drugs, i.e. epinephrine, pilocarpine and atropine, more strongly than the patients with the low basal R.Q. did.13) In 10 patients with NCA and allied disease the changes in the R.Q. were measured during pharmacodynamic test. There was a greater distribution of the R.Q. values prior to and during the test in the NCA group than in the healthy subjects. And in the epinephrine, pilocarpine and atropine tests the mean values of the R.Q. in NCA were always lower than those in the healthy subjects.14) In 95 cases performed myelography, relations between the segment of adhesions and the basal R.Q. were obtained. [the rest omitted]

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As an approach to the problem of the carbohydrate metabolism in essential hypertension, glomerulo-nephritis, arteriosclerosis, neurocirculatory asthenia and other diseases, the author studied the blood suger and related problems in these diseases.Method For the determination of the blood sugar Somogyi's method was used. With regard to the methodology two points appeared to have the crucial importance; one, sufficient caution must be paid to the temperature at which to preserve blood samples after they were withdrawn from the patient; two, a great care must be taken in the process of preparing and preserving the reagent to be used for deproteinizing the blood samples. In view of these existing imperfections of the method, the technique of the blood sugar determination may have to be re-studied and and refined in the future. A total of 230 patients were studied with the following two methods, (a) a load of glucose was injected intravenously in dose of 0.5 gram per kg body weight and in the form of a 20 % solution over a period of 40 minutes by the intravenous drip infusion, and (b) a load of glucose was administered orally in dose of 1.5 gram per kg body weight and in the form of a 50 % solution. After the administration of glucose the blood sugar was determined at different points of time over a period of 3 hours, and the observed patterns of blood sugar variations were examined for the possible correlation with various other clinical tests.Results With the oral administration, the blood sugar concentration returned to the initial level in a retarded manner in the majority of the patients as compared with the control subjects. However, there was a quicker return of the blood sugar concentration back to the initial level than in control subjects in certain cases of acute glomerulo-nephritis and neurocirculatory asthenia, and certain cases of hypertension. With the intravenous drip infusion, however, a greater proportion of the entire group showed normal responses than with the oral administration. Such difference like this, which exists between the oral test and intravenous test, must be something intrinsic to the method of glucose tolerance test itself, and suggests that the two tests must be interpreted differently. In evaluating the subject's ability to dispose of the glucose in a glucose tolerance test, the author depended on the angular coefficient of the ascending and descending limbs of the blood sugar curve. As the result of such a study the following characteristics of various diseases were revealed concerning the patients' glucose tolerance capacity : it was diminished in the essential hypertension both with the intravenous and with the oral test; it was diminished, but to a slighter extent, in the glomerulo-nephritis; it was diminished with the oral test but mostly normal with the intravenous test in the neurocirculatory asthenia.With regard to the relation between the arterial blood pressure and the blood sugar curve, there was an inverse correlation between the systolic blood pressure and the angular coefficient of the ascending limb of the blood sugar curve produced by the intravenous drip infusion. There was also an inverse correlation between the fasting blood sugar level and diastolic blood pressure.Discussion Clinical tests in various disease-groups revealed that functions were impaired in different degree in different diseases; functions relative to the liver, kidneys, endocrine, cardiovascular and autonomic nervous systems were impaired with the greatest severity in the arteriosclerosis, moderately in the essential hypertension, slightly in the glomerulo-nephritis and to the slightest extent, finally, in the neurocirculatory asthenia. It was in the same descending order of the severity that the patient's glucose tolerance capacity was impaired. In the next place, the author examined possible correlations between various clinical functional tests and the fasting blood sugar level or the angular coefficient of

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