A controlled, double-blind study of effects of dl-alpha-tocopheryl nicotinate (vitamin E-nicotinate: EN) for relief of symptoms was performed in 94 patients with hypertension and cerebral arteriosclerosis. Eighty-nine cases (44 cases treated with EN and 45 with inactive placebo) had completed this study, and remaining 5 cases were dropped out.Six capsules of EN (600mg) in the treated group and 6 capsules of inactive placebo in the placebo group were given daily for 4 weeks in all cases, and for 6 weeks in 43 cases. The following results were obtained.
1) The general improvement rating was significantly greater in EN group than that in placebo group (p<0.005).
2) For 5 items of subjective symptoms, the improvement rating of EN was relatively higher than that of placebo. The result of statistical analysis of them was as follows; numbness of limbs (p=0.032), dizziness (p=0.054), stiff neck (p<0.10), heavy feeling of head (p<0.10), and insomnia (p=0.025).
3) The general improvement rating increased consistently as related to the time intervals following the treatment in EN group as follows; 73.7% at 2 weeks, 87.2% at 4 weeks, and 95.2% at 6 weeks intervals. On the other hand, that in placebo group was essentially the same at each time interval as follows; 68.6% at 2 weeks, 61.1% at 4 weeks, and 63.6% at 6 weeks intervals, respectively.
4) No untoward side effects from this agent were observed during study, but a few cases experienced mild anorexia, diarrhea or abdominal discomfort.
From the present results, it can be concluded that EN is a safe and effective agent for relieving various symptoms attributed to hypertension and cerebral arteriosclerosis.

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Electrophysiological and histological correlation was documented in 2 cases of complete heart block (CHB).
Case 1 (77 yrs. female): CHB continued for 1.5 years with normal QRS in axis and duration. The His bundle electrogram (HBE) showed A-H block with normal H-V interval (40 msec). Ten months later she died of bronchopneumonia and paralytic ileus. Histological study of the conduction system revealed a giant nodule of calcification in the mitral ring and central fibrous body, which compressed the end of the A-V node and most part of the penetrating portion of the A-V bundle. Above-mentioned findings were thought to be compatible with A-H block in HBE.
Case 2 (82 yrs. male): His EGG showed CHB with QRS configura-tion of right bundle branch block (RBBB) with left axis deviation (LAD), with transient appearance of RBBB with right axis deviation (RAD) or left bundle branch block (LBBB) patterns. The HBE revealed normal PH interval (120 msec), and the site of block was distal to the A-V bundle. In addition to the H potential, spike 'X' was also recorded 20 msec before QRS wave. He died suddenly after 1.5 years of hospitalization. Histological examination revealed that both anterior and posterior fascicles of the left bundle branch showed severe destruction at their origins, and the right bundle branch also showed marked fibrosis. These histological findings were so-called 'trifascicular block' and compatible with H-V block in HBE. And the meaning of the 'X' spike in HBE was discussed.

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In order to examine the variability of the pattern due to the location and direction of the ultrasonic transducer, echocadiograms of the pulmonary valve were obtained from different precordial areas in 28 patients with various diseases and in 3 normal subjects.
By higher positioning of the transducer, the diastolic slope became slower or upward and the 'a' wave became indiscernible, giving the pattern of pulmonary hypertension even in the normotensives. The anterior cusp was also detected by tilting of the transducer in some cases.
Systolic time intervals (STI) of the right ventricle, however, were not influenced by the beam angle.
The present data strongly suggests that the echocardiogram of the pulmonary valve should be carefully evaluated in the light of the spatial relationship of the echo beam and the valve in order to give the diagnostic importance.

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Effect of postural change on plasma renin activity (PRA) in peripheral and renal veins was studied in hypertensive patients with or without renal artery stenosis (RAS). When a renal venous PRA ratio (higher value to lower value) of 1.5 or more, as an index for predicting surgical curability of hypertension due to RAS, was applied to these patients in the prolonged recumbent position, 3 of the 12 patients without RAS showed false-positive ratios of more than 1.5 with normal values in peripheral venous PRA. On the other hand, 3 of the 7 patients with RAS cured or improved by surgery had normal peripheral venous PRAs, showing a false-negative ratio of 1.1. Re-evaluation of the ratio after passive tilting gave no more the false-positive and false-negative results; the value was decreased in 3 patients without RAS and augmented in 3 patients with RAS. The mean ratio after passive tilting was unaltered in 12 patients without RAS and significantly elevated in 18 surgically and medically treated patients with RAS. After resumption of recumbent position, the disparty of renal venous PRA between the 2 sides disappeared in 4 of the 5 cured or improved patients. The ratio between peripheral and lower renal venous PRAs remained unchanged throughout the postural changes in patients both with and without RAS.
These results suggest that the determination of PRA after passive tilting may propose a more accurate indicator for predicting surgical curability by making the renal venous PRA ratio clearer, especially when peripheral venous PRA shows a normal value.
To obtain reliable results, caution should be taken to keep up continued recumbency before collection of blood for PRA measurement.

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Twenty-four hour recording of electrocardiogram was performed in 5 cases, aged from 42 to 75 years, with paroxysmal tachyarrhythmias (paroxysmal supraventricular tachycardia (PSVT) 2 cases and paroxysmal atrial fibrillation (PAf) 3 cases) for the purpose of assessing the effects of digitalis on sinus node function from the chronobiological point of view. All of the pauses following the termination of PSVT or PAf observed during a day were measured in 4 cases as the sinus node recovery time (SNRT). Corrected sinus node recovery time (CSNRT) was determined by subtracting the penultimate P-P cycle length from the SNRT. Both SNRT and CSNRT were prolonged in all cases after digitalis administration. In 1 case observation on the diurnal variation of SNRT and CSNRT showed the most marked prolongation of these values at 6:00 a.m. after digitalis administration. The second degree of SA block was observed in 2 cases in the early morning after digitalis treatment. In the other 2 cases sinoatrial conduction time (SACT) was calculated by the use of premature atrial contraction and corrected by dividing by the basic cycle length before and after digitalis administration. Neither SACT and CSACT showed significant differences between the values before and after the treatment in 2 cases, nor the diurnal variation of SACT and CSACT showed significant differences. Above results suggest that digitalis should be used with caution in patients with paroxysmal tachyarrhythmia because even small amounts of digitalis might provoke sinus node dysfunction. Twenty-four hour recording of electrocardiogram is useful in the earlier recognition of sinus node dysfunction induced by digitalis.

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Twenty-three cases with WPW syndrome were studied by means of phonocardiography, echocardiography, and electrocardiography. All cases showed the abnormal cardiac motion in echocardiography, which could be divided into 2 types; ventricular (V) type in which the posterior left ventricular wall showed the abnormal humps in the early and late systole (18 cases), and septal (S) type in which the abnormal hump was noted in the early systole in the interventricular septum (5 cases). The cases with V type echocardiogram showed either type A, B, or C, and those with S type either type B or C of ECG. All cases with V type had the splitting of second heart sound of a normal fashion and the IIA-IIP interval ranged from 0.015 to 0.08 sec with a mean of 0.0356±0.0157 sec. In contrast, those with S type showed either a reversed splitting of second heart sound (4 cases) or a single second heart sound (1 case), and the IIA-IIP interval ranged from 0 to -0.05 sec with a mean of -0.0250±0.0170 sec. No consistent relationship was noted between the EGG type and the split interval of second heart sound. There was the significant positive correlation between the IIA-IIP interval and the QRS duration in the cases with V type echocardiogram. In S type, these 2 parameters showed the significant negative correlation.

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The fourth heart sound was clearly recorded by using the signal averaging method. Furthermore, the simultaneous recording of the Doppler signal with the fourth heart sound was performed. Thus, it was demonstrated that the Doppler signal started after the P wave and followed by the fourth heart sound. In 2 cases, the effect of the double Master's test and taking a bath was studied on the computer averaged phonocardiogram. After the exercise, the amplitude of the fourth heart sound was increased, whereas after taking a bath it was almost unchanged. The above results show that the simultaneous recording of a computer averaged phonocardiogram and Doppler signal that is associated with cardiac activity can greatly facilitate the interpretation of small vibrations such as the fourth heart sound.

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Serum dopamine-β-hydroxylase (DBH) activities of 74 apparently healthy adults were not distributed normally, but skewed to the right. There were at least 2 subgroups in the distribution of DBH activity. Accordingly, 27 serial serum DBH activities following acute myocardial infarction were divided into 2 subgroups according to their activities on the 10th day or/and thereafter. The DBH activity was significantly elevated on the 1st day with average of 157% of the 10th day (p<0.015) in high DBH subgroup and also significantly elevated on the 1st and 2nd day with the average of 182% and 155%, respectively, of the 10th day (p=0.025 and p<0.05) in low DBH subgroup. There was no significant difference between the DBH activity of patients with anterior myocardial infarction and that of patients with inferior myocardial infarction. No significant correlation between the DBH activity and the coronary prognostic index was found.
The observed elevation of the DBH activity on the 1st and the 2nd day suggests an augmentation in the sympathetic nervous activity after acute myocardial infarction.

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Blood-letting of 450 to 1, 000ml with or without saline infusion was performed in dogs. In some dogs, right atrial pacing was carried out during blood-letting. Heart rate and isometric time-tension index were measured as the indicators of chronotropism and inotropism, respectively. After 60 min of blood-letting, dogs were sacrificed and mitochondria were isolated from the left ventricular myocardium. Mitochondrial respiration was measured polarographically and respiratory control index was calculated.
As blood-letting advanced, the hearts revealed negative chronotropism with negative inotropism. Mitochondrial respiration was suppressed. When heart rate was forced to increase with atrial pacing, the hearts showed positive chronotropism with negative inotropism. Respiratory control index of mitochondria was deteriorated, showing uncoupling of oxidative phosphorylation.
In consideration with our previous study on the ischemic heart, it is concluded that uncoupling of oxidative phosphorylation appeared in hypoxic myocardium when cardiac dynamics shifted to positive chronotropism with negative inotropism, though suppression of mitochondrial respiration was revealed when cardiac dynamics altered to negative chronotropism with negative inotropism.

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The hemodynamic and metabolic changes, during coronary occlusion and during coronary perfusion with non-oxygenated solution, were studied in anesthetized dogs.
Coronary perfusion with non-oxygenated Tyrode's solution was performed through a cannula inserted into the left circumflex coronary artery. Left ventricular peak systolic and end-diastolic pressure (LVSP and LVEDP) were measured, and peak LV-dp/dt/IIP calculated. Stroke volume was measured, and the changes of the local myocardial segment length were recorded by a strain gauge arch sutured on that portion of the myocardium perfused through the left circumflex coronary artery. The efflux of lactic acid into the venous blood from the myocardium perfused through the left circumflex coronary artery was calculated.
After 10 sec of coronary occlusion, LVSP, SV, and peak LV-dp/dt/IIP declined; LVEDP elevated and a systolic bulge appeared on the local myocardial segment length curve. There was almost no change in these parameters during 3 min of perfusion with non-oxygenated solution. The efflux of lactic acid was more marked during the perfusion with non-oxygenated solution than during coronary occlusion.
The delay of the depression of cardiac function during perfusion with the non-oxygenated solution could be related partly to the "washout" of metabolites, such as lactic acid, accumulated in the anoxic myocardium.

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The effects of potassium chloride were studied on pacemaker activity in the sinoatrial (SA) node and on contractility in isolated, blood-perfused atrial and left ventricular preparations of dogs, which were suspended in the bath and perfused with arterial blood from the carotid artery of the heparinized support dog. Potassium chloride given directly into the sinus node artery in a dose range of 100μg-1mg produced a doserelated positive chronotropic and a negative inotropic effect in isolated atrium preparations. Potassium chloride into the cannulated anterior descending branch of the left coronary artery caused only a negative inotropic effect in isolated ventricular preparations. A larger dose of potassium chloride caused temporary atrial or ventricular arrest. These effects of potassium chloride were not modified by pretreatment with atropine or propranolol.

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Hematocrit can be increased in experimental animals with renal hypertension of two-kidney type. The present study showed that the increased hematocrit was returned to normal by removal of the clipped kidney.
The left renal artery was clipped in 13 rabbits with an intact contralateral kidney, and a sham operation was performed in 10 rabbits as a control. After an interval of 10 weeks the left kidney was removed in all animals. Blood pressure, hematocrit, hemoglobin content, and erythrocyte count were rapidly increased and remained raised after clipping of the renal artery but they did not show any significant changes after sham operation. A transient but significant increase of reticulocyte count was found at the end of the first week after clipping of the renal artery. Removal of the clipped kidney was followed by a rapid return of hematocrit, hemoglobin content, and erythrocyte count to normal within 2 weeks. Blood pressure was also decreased but not returned to normal by removal of the clipped kidney.

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The effect of chronic oral administration of propranolol (39-80mg/Kg/day, for 21-27 days) on blood pressure, plasma renin concentration, and heart rate were studied in 2 types of renovascular hypertensive rats; one-kidney type with normal plasma renin and two-kidney type with high plasma renin. No significant change was observed in the blood pressure of either model during the administration of propranolol in spite of a significant reduction of heart rate. Plasma renin concentration showed a trend of suppression in two-kidney type rats, but this change was not significant. There was no suppression in one-kidney type rats. These results suggest that the beta-adrenergic system may not play a major role either in regulating plasma renin level or in maintaining the blood pressure in renovascular hypertensive rats.

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Using isolated, blood-perfused atrium preparation of the dogs, the effect of stretch on sinus rate was studied in 11 preparations. Stretching usually produced sinus acceleration in all 11 spontaneously beating atria. Within a range of 0-30Gm, greater degrees of stretch produced greater degrees of sinus acceleration. During maintained stretch sinus rate slightly reduced but not to the control rate. On release from stretch sinus rate immediately returned to the control rate, and there was occasionally a slowing to rates lower than control in verapamil treated preparations. Atropine, adrenergic beta-receptor blocking agents, propranolol and carteolol, verapamil, and tetrodotoxin did not greatly modify responses to stretching.

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An analysis of 69 cases of bifascicular and trifascicular types of intraventricular conduction disturbances in myocardial infarction is presented. Complications, causes of death and the follow-up of unpaced cases for a year have been recorded. Pump failure and severe degrees of blocks with consequent ventricular asystole are the important causes of death. Recurrent pump failure with occasional fatal outcome is more common in cases with RBBB and LAH than in other types of blocks.

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