Progress in the antibiotic treatment facilitates management of rickettsiosis. Treatment with tetracycline and its derivatives in the dosis described elsewhere, however, is complicated with relapse frequently. To prevent this relapse avoiding physical and economical inconvenience of the patient, principle of small-amount and long-term antibiotic treatment of rickettsiosis was established by Katsura and his associates. The gradual defervescence during the treatment in this principle might cause irreversible disturbances to the patient treated.The purpose of present report is to know whether irreversible changes in cardiovascular system would occur or not, during the course or treatment in this principle. For this purpose electrocardiographic tracings of thirteen cases on naturally infected tsutsugamushi disease and twenty-four cases of inoculated rickettsiosis, as a pyrotherapy of metasyphilis, are studied.In three of thirteen natural cases of tsutsugamushi disease minor changes in ST-T segment are observed. But the changes in two cases are so slight that they are usually neglected in routine clinical practice. The changes above mentioned are observed in the febril stage.In fourteen of twenty-four inoculated cases, the same changes are observed but they are also very slight in twenty cases. Difference between the frequency of occurrence in natural and inoculated cases is chiefly due to the following conditions. (i) All inoculated cases are suffering from syphilis in various forms. (ii) All of them are elder than natural cases. (iii) Duration of febril stage in inoculated cases is always longer than natural cases because of necessity for pyrotherapy. (iv) The same patients are successively inoculated with the other rickettsiae and included in cases described if his symptoms are not subsided.No significant differences in electrocardiographic findings are observed among the cases inoculated with R. tsutsugamushi (Niigata and or Shichitostrain), R. tamiyai, and R. sennetsu.The tracings after the complete defervescence reveal no persistent changes.

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Pathological changes in myocardial infarction usually appear later than the electrocardiographic and quantitative biochemical changes. In order to study this discrepancy, systematic studies of the histochemical changes are carried out in experimental myocardial infarction produced by coronary artery ligation.Method : Twenty-three adult mongrel dogs were used. Myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery between the first and the second left ventricular branch attempting to exclude the accompanying veins and nerves. Animals were killed at the following intervals, 1, 1 1/2, 2, 3, 4, 10 hours, 1, 2, 3, 4, 5, 6, 7, 9, 11, 16, 23, 64 and 155 days, and specimens were obtained. As histochemical methods, several enzymes such as succinic dehydrogenase (tetrazolium method), acid and alkaline phosphatase, ATP-ase, lipase, periodic acid Schiff method with and without saliva digestion, metachromasia by toluidine blue, Rinehart's colloidal iron stain, lipid (Sudan black B and Sudan IV), calcium (Kossa and alizarin method) were stained and at the same specimen, Haematoxylin-Eosin, Mallory, Goldner-Masson and elastic fiber stain (Gomori's method) were used.Results : 1. Areas of myocardial degeneration were not evenly distributed, but showed varying degrees of pathological change in a mottled appearance, even in the anterior wall of the left ventricle which showed most remarkable change.2. The earliest histochemical change was a loss of glycogen. After one hour, a marked reduction of glycogen content was noticed without accompanying histological changes. After one day, glycogen of myocardial fibers completely disappeared but at the border of the degenerated or fibrotic area, more than normal amount of glycogen appeared and lasted for several days.3. The neutral fat droplet appeared in myocardial fibers after 3 hours, which were deeply stained with eosin preserving their fine structures. The lipase activity was recognized more distinct in broader area. After 10 hours, fatty degeneration became prominent and 5 to 6 days later, as myocardial fiber became necrotic, neutral fat and lipase activity disappeared. The fatty granular cells, and infiltrated leucocytes showed a distinct activity of lipase. Calcium deposition was seen about the same area and disappeared along with fat droplets.4. The succinic dehydrogenase activity did not decrease within first several hours of infarction and showed a decreased activity after 10 hours. After one day, this activity became completely negative in the same area and after 3 to 4 days, it became completely negative transmurally. The muscle fibers which lost this activity stained deep with eosin uniformly, and showed coagulation necrosis.In the media of arterial wall in the myocardium, faint activity was demonstrated, gradually decreasing with the progress of the myocardial change.5. The activity of ATP-ase and acid phosphatase in myocardial fibers decreased gradually paralleling with succinic dehydrogenase activity. Alkaline phosphatase activity was seen in the capillary walls but muscle fiber showed only a faint activity, so that the influence of circulatory arrest was not evident.6. After 3 to 4 hours, some degenerated muscle contained PAS positive substance and not affected by saliva digestion. This was also metachromasia positive in PH 4.1 of toluidine blue and suggested the presence of acid mucopolysaccharide contained a hyaluronic acid. After 3 to 4 days, newly formed connective tissues showed a remarkable acid mucopolysaccharide reaction contained a sulfate compound, that is metachromasia positive in PH 2.5 of toluidine blue and colloidal iron stain positive. When the connective tissue became older, these reactions were reduced gradually.7. Electrocardiogram was taken directly from the epicardial surface.

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It is known that coronary insufficiency is chiefly due to coronary sclerosis, but gradual coronary occlusion does not cause a myocardial infarction. On the course of clinico-pathological studies on myocardial infarction, about a half of cases showed only a narrowing of corresponding coronary artery. The present investigation is a histochemical and pathologic study of myocardial infarction produced by acute coronary constriction.Method : Twenty-three adult mongrel dogs were used. Coronary constriction was produced by U-shaped silver clamp (0.7-1.0 mm in inner diameter) to clip the same artery as reported in the preceding paper. Animals were killed after 3 hours to 131 days of ischemia. Histochemical, histological and electrocardiographic methods were the same as in the first report.Results : 1. In histochemical studies, loss of glycogen and appearance of fatty droplets in muscle fibers were seen in early stage, but these changes seemed to be reversible as 3 to 5 days later most of the myocardial fibers regained their normal staining paralleled with the recovery from edema and degeneration. On the other hand, loss of succinic dehydrogenase, ATP-ase and acid phosphatase activity, and appearance of acid mucopolysaccharide reaction in muscle fibers, were accompanied with the destruction of their fine structures and seemed to be irreversible changes.2. After one day, a slight degeneration of muscle fibers was seen in full layers of the anterior wall of the left ventricle, but two to three days later, most myocardial fibers recovered from degeneration, and only a part of subendocardial muscle layer and a border of muscle bundles (deep sinospiral and deep bulbospiral) showed a minor degree of myocardial necrosis. This indicated that a collateral circulation could develop within two to three days following coronary constriction.3. Coronary arteries showed marked edema of its wall in early stage, then regenerative processes took place gradually and intimal hyperplasia such as fibroelatosis narrowed the lumen. These changes formed a contrast to histolytic changes seen in coronary artery ligation. Fibrinoid necrosis was seen in the arteries beyond the occluded area in two cases.4. In most cases, early changes of myocardial necrosis were seen in posterior wall, especially in subepicardial layer or a border of muscle bundles. These were seen in old infarction which showed only a interstitial fibrosis in the anterior wall. These findings could indicate the presence of functional circulatory disturbance and intercoronary reflex mechanism.5. Electrocardiogram taken directly from epicardial surface revealed the following : The elevation of RS-T segment was seen 1/2 to two minutes after the constriction, reaching its maximum in two to five minutes. After sixty to ninety minutes, RS-T segment returned to former level, then turned into the coronary T inversion. The coronary T inversion became positive around three to four days. Neither QRS changes nor extrasystoles were seen. Depressed RS-T segment was seen in 3 cases. In 2 cases of marked subendocardial infarction, electrocardiographic abnormalities were not observed.

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During the course of the investigation on the electrolyte metabolism in cardiovascular and renal patients, our attention was called to the great variance of sodium content of blood cells, in contrast to the constancy of the electrolyte in blood plasma except in extremely severe states. While many works have been made on the electrolyte changes in the extracellular fluid in diseased states, little is known about the changes in the intracellular phase.In this paper the results of the estimation of the contents of sodium and potassium in blood cells and plasma in 81 cardiovascular and renal patients and 22 normal subjects are reported and their clinical meanings are studied. The concentrations in cells were calculated from the values of whole blood, blood plasma and hematocrit.The results are as follows : 1. In normal subjects, sodium and potassium concentrations in blood cells were 11.4±7.05 mEq/L (13.5±7.12 mEq/kg H₂O), and 87.5±6.08 m Eq/L (127.5±12.33 mEq/kg H₂O) ratio of the total sodium and potassium concentration in blood cells to that in blood plasma was 0.69±0.07 in mass volume or 0.90±0.099 in water.2. In non-edematous cases, including essential hypertension, all the above values and ratio were within normal ranges. In edematous patients the sodium concentration and the ratio described above were in general significantly higher, except the ratio in 2 nephrotic cases : In edematous chronic glomerulonephritis and nephrosclerosis, sodium concentration 42.8±16.87 mEq/L, potassium concentration 83.7±10.54 mEq/L, the total concentration 126.4±20.56mEq/L, the ratio 0.93±0.15. In edematous cardiacs, 19.1±18.1 m Eq/L, 95.5±10.87mEq/L, 115.1±18.10 mEq/L, 0.83±0.153, and in nephrosis, 22.6mEq/L, 79.4 m Eq/L, 101.5 mEq/L, 0.71, respectively.3. The cell sodium concentration was negatively correlated to the cell potassium concentration but the total concentration of sodium and potassium can be markedly elevated due to the sodium increase in cells. In edematous subjects, sodium and potassium contents of blood cells and the total contents of the two were negatively correlated to the corresponding values respectively. No such correlation was seen in non-edematous subjects.4. Systolic blood pressure, glomerular filtration rate and total plasma protein were correlated to the sodium concentration of blood cells in some degree, but not to the potassium contentration. The latter was in reversed correlation to the hematocrit value.5. Sodium concentration in blood cells is increased in severe stage of cardiovascular and renal diseases. This increase may be the result of the reduced metabolic function of blood cells.

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In experiments with seven dog's heart, the author took direct lead ECG simultaneously recorded over the surface of the right and left atrium after locally ligating a place around the sinus node, or the Bachmann's bundle, or the atrial wall etc., and compared one with another of the activation times for both atria before and after the ligation by means of the intrinsic deflection of the P wave, and studied the change in the times of stimulus arrival at both atria. Here a minute histological search on the aspects of the ligated portions was made by Osawa. Following are the results of all these experiments.1) In five cases the Bachmann's bundle was ligated, stimulus arrival at the left atrium immediately after ligation was later by 0.017-0.342 second or 0.092 second on the average than before the ligation took place. But in right atrium no change has occurred. Doubtlessly these facts show that the stimulus conduction from the sinus node to the left atrium was chiefly carried out through the Bachmann's bundle.2) In a case the tail of the sinus node was ligated activation arrival at the right atrium immediately after the ligation was not delayed. However, when the fact is considered that the lead point in a right atrium was the middle part of its anterior wall, we should, concerning the stimulus conduction between the sinus node and the right atrium. suppose the existence of the stimulus conduction pathway that proceed from the head or trunk of the sinus node, other than a pathway that proceeds from the tail of the sinus node.3) In case the Bachmann's bundle, the anterior wall of the right atrium, and the tail of the sinus node were ligated all at the same time P-Q interval in both atrial curve was shortend, that was immediately after the ligation, namely the activation arrival at both atria was delayed. No variation regarding conduction however, was detected in the Tawara's node.This is because, in this instance, the main conduction pathways that stimulus proceed from the simus node to the right atrium and from the sinus node to the left atrium were simultaneously all intercepted, while the pathway from the sinus node to the a-v node was maintained in a perfect condition.4) In an instance, when a greater part around the sinus node excluding the tail was ligated the activation arrival at both atria immediately after ligation was found considerably delayed, in this case supposedly due to the fact that either of the main pathways leading to points on both atria had been intercepted.5) In the experiments above there were three instances in which a complete disturbance of conduction between the left and right atria was unexpectedly observed, the occurrence of which could be easily explained by way of affirming the existence of the specific stimulus conduction pathway between the sinus node and the right atrium, and between the former and the left atrium.In short, stress has been placed on the assertion that there may exist specific conduction pathways rendering direct connection between the sinus node and both the atria through their respective pathways.

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During the recent years, rapid progress has been made in the patho-physiological examination of the respiratory function in pulmonary tuberculosis. However, the methods used to examine the various factors such as ventilatory function, alveolar function and pulmonary circulation are mostly complicated and the load on the examinee is usually quite large. Therefore, these tests are not suitable as routine tests to be done before and after surgical treatment of pulmonary tuberculosis, in order to examine the changes in the pulmonary function which occur. However, the pulmonary function can not be determined by simple procedures such as the measurement of vital capacity and arterial blood gas analysis. In this respect, the oximetric rebreath test (O. R. T.) originated by Hara and Mito in our Department can be done relatively simply and without much load on the patient. Thus a study was planned to see whether the O.R.T. can be used as a test of pulmonary function which will adequately show the influence of various types of thoracic surgery on the oxygen intake of patients with pulmonary tuberculosis.

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