The nervous control of the coronary circulation has been widely investigated, but many problems still remain unsolved. It is generally accepted that the coronary vessels are dilated by the sympathetic nerve and constricted by the vagal nerve. However, recent work of our clinic stands against these former concept. In this paper, for further study of the nervous control of the coronary vessels from pharmacological standpoint, the effects of some autonomic drugs on the coronary circulation were investigated.Young dogs with open-chest and artificial respiration, ranging in weight from 10 to 15 kg, were used under sodium thiopental (Ravonal) anesthesia. The left coronary artery was perfused from the animal's own right femoral artery and the coronary inflow was measured with rotameter. Then one ml. of drug solution, which contained 1×10^-9-10^-4 gm epinephrine, 1×10^-3-10^-4 gm norepinephrine, 1×10^-9-10^-5 gm acetylcholine, or 1×10^-7-10^-4 g ATP^-Na, were injected into the tubing leading to the coronary artery from the rotameter using 10 seconds, and the changes of coronary blood flow were calcutated.Results were as follows : 1) Doses above 1×10^-3-10^-7 gm of epinephrine increased coronary flow. In these cases, the coronary flow was increased slowly after the injection and duration of the increase in coronary blood flow was comparatively long. It often lasted several minutes. The increase in coronary blood flow was almost always associated with the elevation of blood pressure and change of heat rate. When large doses of epinephrine was injected, initial decrease in coronary blood flow was followed by a marked increase.2) The effect of norepinephrine was essentially the same as that of epinephrine in quality. Doses above 1×10^-7-10^-6 gm of norepinephrine increased coronary blood flow, heart rate and blood pressure. Long sustained increase in coronary blood flow was observed. When large doses were injected, initial decrease was also observed.3) Injection of small doses of acetylcholine or ATP-Na often increased the coronary blood flow without remarkable changes of blood pressure or heart rate. Large doses of acetylcholine (1×10^-6gm or more) decreased heart rate, blood pressure and coronary blood flow. The effects of acethylcholine and ATP-Na on coronary blood flow appeared more rapidly than those of epinephrine, but lasted for 15-30 seconds.4) As mentioned above, acetylcholine and ATP-Na increased coronary blood flow without remarkable changes of heart rate and blood pressure, but in no experiment epinephrine or norepinephrine augmented the coronary blood flow without any evinence of irritation of myocardium, such as elevation of blood pressure, increase in heart rate and vigor of myocardial contraction. Therefore it can be concluded that in this experiment the direct coronary vasodilatative effects of acetylcholine and ATP-Na were demonstrated, but such effects of epinephrine and norepinephrine were not observed. From present data the presence of the direct action of epinephrine and norepinephrine cannot be decided. But in seems that the direct action of these drugs are vasoconstrictive to coronary artery. At least it appears that the coronary vasodilatative effects of these drugs chiefly result from the hemodynamic and metabolic changes induced by their effects on the myocardium.

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The CERO₂, composite factor of the balance of supply and demand of oxygen in the brain, not only expresses the presence and intensity of cerebral anoxia objectively but also seems to be an important compensatory factor in the maintenance of the normal cerebral function. The circulation and metabolic function in the brain were regulated in two ways by the blood flow regulating mechanism in and outside of the brain and by the compensatory change in CERO₂ of the cerebral tissue itself. The metabolic disturbance of the brain appears to be evoked by the insufficient compensation of CERO₂. Taking into consideration that the results obtained by N₂O method which state that the decrease in cerebral metabolism of the aged people is a secondary phenomenon of the decrease in oxygen supply to the brain, mainly the decrease in CBF, it is supposed that CERO₂ in the aged people should be greater than normal young people. Usually an inverse correlation is assumed between CBF and CERO₂. As the CBF of the aged is mainly due to the asteriosclerosis of the brain, a certain kind of correlation is inferred between CERO₂ and cerebral arteriosclerosis.The present author, to study the correlation between CERO₂ and cerebral arteriosclerosis, has measured CERO₂ in healthy and anemic aged subjects, examined the clinical significance of CERO₂ by comparing to the results obtained by N₂O method, retinal findings, cerebral symptoms and autoptical findings, and obtained the following results.1. The increase in CERO₂ was observed in about 70% of healthy aged subjects. Such frequent cerebral anoxia in healthy older people suggests the possibility of cerebral anoxia and cerebral metabolic disturbance in the aged.2. The assumption that the difference in CERO₂ in healthy aged subjects in caused by the abnormality of cerebral hemodynamics (decrease in CBF and increase in CVR) was confirmed experimentally and by the results obtained by N₂O method.3. The fact that this increase in CVR reflects mainly the attitude of the sclerotic cerebral arteries was examined by the correlation between retinal findings, cerebral symptoms and CERO₂.4. From the above stated results it is inferred that CERO₂ may be applied clinically as a measure of the intensity of cerebral arteriosclerosis.5. However, when anemia, disturbance in pulmonary function, abnormality of cerebral oxygen supply due to other CBF diminishing factors than cerebral arteriosclerosis, or primary metabolic abnormality of the brain is present, some considerations to such abnormal conditions are required.6. In anemic aged people, when the abnormality of the cerebral circulation is intense, anemia acts facilitatory to cerebral anoxia.7. Therefore, in this case, it is supposed that the CBF estimated from CERO₂ takes a value lower than the actual level and that CVR and the intensity of arteriosclerosis take higher levels.8. The intensity of cerebral arteriosclerosis increased in parallel with CERO₂ in the autoptical findings and the hypertensive subjects who increased in CERO₂ has a tendency of cerebral apoplexy. From this results it is inferred that CERO₂ may be applied as a critical signal of cerebral apoplexy too.

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The 2nd Experiment : The adrenocortical function in experimental renal hypertensive dogs.The author made experimental hypertension in dogs by Goldblatt's or Page's method, and measured 17-KS excretion in urine comparing with histochemical examination of the adrenal cortex.EXPERIMENTAL PROCEDURE 1. Goldblatt's method : The main renal arteries on both sides were ligated in 7 of 12 dogs. In other 5 dogs which were nephrectomized unilaterally, the main renal artery of the remaining kidney was ligated. After the operation they were observed for 38 to 284 days.2. Page's method : One side of kidney was covered with cellophane or silk cloth in 8 dogs, and then other side was treated with the same procedure. After the operation they were observed for 28 to 107 day.RESULTS 1) Blood pressure a) Blood pressure of normal dogs. According to the examination of 46 normal dogs, blood pressure showed 90-150 mmHg, and on the average 125±9.7 mmHg, 40% of 46 dogs showed 120-130 mmHg, 20% 110-120 mmHg, and 20% 130-140 mmHg.b) Blood pressure of experimental dogs. The elevation of blood pressure was classified into three classes, i.e. slight elevation (below 150 mmHg), moderate (150-170 mmHg) and severe (above 170 mmHg).(α) In 12 Goldblatt's dogs two showed slight and four severe hypertension. Ratio of success in production of hypertension was 50%.(β) In 8 Page's dogs one showed slight, one moderate and two severe hypertension. Ratio of success was therefore 50%.2) 17-KS excretion in urine a) 17-KS excretion in urine of normal dogs. In 16 males it showed 0.1-0.97 mg/day and in 12 females 0.04-0.75 mg/day.b) 17-KS excretion in urine of experimental dogs.(α) Goldblatt's dogs. On the day of operation, it showed a marked decrease and then gradually increased to reach the highest value. After that it decreased and restored the preoperative value. 17-KS had nothing to do with blood pressure.(β) Page's dog. On the day of operation, it showed a marked low value and then gradually increased to reach the highest level. After that it decreased to the preoperative level. 17-KS level and blood pressure did not necessarily go parallel.3) Histochemical study of the adrenal cortex Parallel to the elevation of blood pressure the zona glomerulosa showed a hypertrophy, i.e. hyperfunction, and the zona fasciculata showed the findings of stress. From the findings of zona glomerulosa this layer or the adrenal cortex seems to be related to the renal hypertension.The 3rd Experiment : The functions of adrenal cortex in experimental DCA hypertensive rats.The author treated rats with DCA and salt to make hypertension, and the measurement of 17-KS excretion in urine and histochemical examination of adrenal cortex were made.EXPERIMENTAL PROCEDURE The author used 9 male rats, weighing 130-240 g, which were divided into three groups, each group consisting of three rats. The first and second groups were injected subcutaneously with 5 mg of DCA every second day. And the first and third groups were given 1% salt solution to drink and the second group distilled water.RESULTS 1) Blood pressure a) Blood pressure of normal rats. Mean value of 74 normal rats was 106.8 mmHg and standard deviation 48 mmHg.b) Blood pressure of experimental rats. In the first and second groups, blood pressure began to rise on the 10th day. On the 40th day it reached 200 mmHg in the first group, but 147 mmHg in the second group, which therefore showed a much slighter increase than in the first group. In the third group, no change was observed in blood pressure. Before death, the blood pressure was measured at 110 mmHg.2) 17-KS excretion in urine a) 17-KS excretion in urine of normal rats. 3 days' urine of a pair of rats was used to measure its 17-KS excretion in 26 normal rats and 2 days' urine of each three rats in other 9. This measurement is, therefore, considered as 17-KS excretion of 6 rats in one day's urine, which showed 14 to 95γ.

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In six cases when dog's heart were used the unipolar lead ECG simultaneously recorded was taken over the surface of the right and left atria after the atrial septum was ligated, to study possible variation that might take place in the P-Q interval before and after the ligation, that is, to study any effect that the septum ligation might have on the stimulus conduction between the sinus node and the Tawara's node.Here again Osawa worked out a minute histological research on the ligated portion by way of finding its relation with the four pathways, which he had previously reported as activation pathways between the sinus node and the Tawara's node.Summarized below are the results of all these studies.1) In two of the six above cases, when, out of the four pathways assumed by Osawa in his histological research, the two running through the atrial septum were completely ligated, no impediment was found done to either the Tawara's node or His's bundle. In each of these two cases a remarkable prolongation of 0.025-0.050 second immediately after ligation was noted in P-Q interval as compared with that before ligation.2) In each of the other four cases, after a histological research, impediments to various extents were found done to Tawara's node and His's bundle causing in these cases an extraordinary prolongation of 0.067-0.217 second in the P-Q interval immediately after ligation, as compared with that before ligation, and in three out of the four cases a-v block and ventricular fibrillation occurred within three minutes.From what have been said above, two cases may be looked into concerning the prolongation of the P-Q interval in the clinical ECG; one when there is an injury done on the conducting pathway connected between sinus node and the Tawara's node, and the other when there is an injury done on the Tawara's node or the His's bundle.It is however, almost impossible to tell, by means of the length of the prolongation of the P-Q interval, which cause may be taken to account, when it is taken into consideration that the injuries done to the pathways must differ every way in extent. Be that as it may, the theory, that the stimulus conduction between the sinus node and the Tawara's node is performed through the definite stimulus conducting pathways, could undoubtedly be said to have been proved as a result of all above experiments.

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