Echocardiographic motions of right ventricular anterior wall (RVAW) were investigated in 71 patients with Wolff-Parkinson-White (WPW) syndrome. According to the criteria of Rosenbaum et al the electrocardiograms were classified as type A in 35 patients and type B in 36. Sixteen type B patients exhibited abnormal RVAW motion, which was characterized by an early onset of the posterior movement before S1 and also by a premature peak formation before S2. A small step or hump nearly coincident with S1 was observed in 10 of these 16 patients. These findings seem to suggest that both contraction and relaxation of RVAW begin earlier than normal due to anterior right ventricular pre-excitation. RVAW motion was normal in all of type A patients. Echocardiographic investigation of RVAW motion appears to be useful in non-invasive estimation of the site of pre-excitation, especially in type B WPW patients

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Spatial characteristics of the QRS and T loops in 110 patients with old myocardial infarction were analysed in comparison with 221 normal subjects. Measured were (1) QRS and T polar vectors, (2) initial 20- and 30msec segmental QRS polar vectors, and (3) length, width, thickness, and ratios of width/length and thickness/length of the QRS and T loops in edgewise and broadside projections. Broadside and edgewise projections were obtained by transformation of the reference frame of the Frank lead system to a patient's own frame based on the polar vector
The recognition rates of abnormality in the QRS and T polar vectors were 66% and 60% of a total of 110 patients with myocardial infarction.The initial 30msec segmental QRS polar vector showed the highest recognition rate of abnormality in myocardial infarction, i.e., 87% in anterior myocardial infarction, 100% in extensive anterior myocardial infarction and 78% in inferior myocardial infarction. The initial segmental QRS polar vector was abnormally deviated posteriorly and superiorly in inferior myocardial infarction. In anterior myocardial infarction, the initial segmental polar vector was directed inferiorly in more than 50% of the cases, while the vector in normal subjects was located superiorly and to the left
The QRS loop of anterior myocardial infarction was significantly smaller in the width and width/length ratio and significantly larger in the thickness and thickness/length ratio than those of the normal. Poor planarity of the QRS loop was one of the characteristics of myocardial infarction, especially of extensive anterior myocardial infarction. The T loop of myocardial infarction was significantly larger in the width/length ratio than that of the normal. More than 50% of the cases with anterior myocardial infarction showed abnormally wide T loops
The polar vector was a useful index to characterize the spatial orientation and sense of rotation of the spatial loop. In addition, the initial segmental QRS polar vector represented the mild localized abnormalities of the spatial loop. The loop configuration in space was characterized in edgewise and broadside projections

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The effects of l-penbutolol and dl-propranolol on A-V conduction, on excitability of ventricular muscle, and on ventricular tachycardia threshold in acute ischemia were compared, using anesthetized dogs
1. L-penbutolol (100μg/Kg) and dl-propranolol (100μg/Kg) prolonged A-V conduction and reduced excitability of ventricular muscle significantly. L-penbutolol less prolonged A-V conduction than dl-propranolol
2. Both l-penbutolol (50μg/Kg) and dl-propranolol (50μg/Kg) significantly prevented the lowering of ventricular tachycardia threshold in acute ischemia
These beta-blocking drugs are effective in the treatment of arrhythmia and l-penbutolol could be used safely, because of its weaker inhibition on A-V conduction

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The effect of oral administration of diltiazem, a new 1, 5-benzothiazepine derivative, on the frequency of anginal attack at rest was studied in 8 patients. Our own experience showed that diltiazem gave excellent results in patients with ST elevation (variant type) but its effect was insufficient in the patients whose ST segment was depressed during the attack

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Serum concentrations of digitoxin and digoxin were measured in 145 cases with various heart diseases receiving maintenance doses of digitalis.Digitalis toxicity was seen in only 2 cases (1.4%)
Day-to-day variation of serum concentration while taking the same daily dose was small in digitoxin therapy (13.8%), but a considerable variation was seen in digoxin therapy (24.4%)
Serum concentrations of both digitoxin and digoxin were measured in the patients receiving digitoxin, and there was a positive correlation between the two (r=0.66, p<0.001). This fact suggested that the effect of digitoxin was the sum of the effects of digitoxin and its metabolite, digoxin. In the patients taking digoxin, digitoxin was not detected in the serum
Serum digitoxin level had a significantly positive correlation to serum albumin level, presumably because digitoxin was retained in serum in the bound form to albumin. Minimal effective level, 10ng/ml, was however obtained with higher daily dose of digitoxin in patients with lower serum albumin

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Responses to the changes in dietary sodium and posture were investigated in 9 young clinically healthy Japanese males who customarily consumed a larger amount of salt than North Americans or Europeans of mixed white ethnic background. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary aldosterone excretion rate (AER) differed at each end of 3- to 4-day spans on a "control", a high-salt and a low-salt diet and of furosemide administration. PRA and PAC, also determined during the upright position following the supine blood sampling, increased after only 1 hour of standing in each condition (p<0.05 or more). PRA and PAC were well correlated in all 4 conditions, regardless of the posture (r=0.806, p<0.001). There were also highly significant correlations between the "supine" PRA or PAC and the preceding 24-hour AER (r=0.869, p<0.001 for PRA; r=0.855, p<0.001 for PAC). Correlation coefficients between PRA and PAC in 9 individual subjects ranged from 0.823 to 0.987. The estimates of constant and slope of the regression line between PRA and PAC varied from subject to subject. The renin-aldosterone axis in response to changes in dietary sodium and posture must be individually assessed

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Twenty-two cat hearts were perfused according to Langendorff technique and myocardial regional ischemia was induced by occlusion of left anterior coronary artery. Separation of particulate (bound) from soluble (free) fraction, and subsequent fractionation into plasma membranes, lysosomes, sarcoplasmic reticulum, and mitochondria were performed by sucrose density gradient ultracentrifugation. By ischemia for 60min, particle bound activity of cathepsin D decreased from 4.2±0.24U/mg protein to 3.2±0.31U/mg protein (p<0.01). Likewise, the particle-bound activity of β-glucuronidase decreased from 11.9±0.92U/mg protein to 6.2±128U/mg protein (p<0.01). Accordingly, free/bound activity ratios of cathepsin D increased from 0.8 to 1.9 and β-glucuronidase from 0.9 to 2.8, respectively. Conspicuous fall from 12.8±0.6U/mg protein to 8.0±0.97U/mg protein (p<0.01) in absolute specific activity of cathepsin D bound to the lysosomal fraction, presents definitive evidence of lysosomal release of the acid hydrolases during the early phase of myocardial ischemia. Electron microscopic observation of the ischemic myocytes revealed ultrastructural alterations of the lysosomes suggestive of autophagic degradation of various subcellular organelles

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To investigate the mechanism of chlorpromazine (CPZ)-induced ventricular arrhythmia, the changes in ventricular fibrillation threshold (VFT) were followed after intravenous injection of CPZ (1mg/Kg) in dogs. Following injection, VFT was decreased to 56.6±5.4% (mean±SE) of the initial level. Since flavin-adenine-dinucleotide (FAD) combines specifically with CPZ in vitro, we investigate whether or not prior treatment with FAD prevents the CPZ effect. With FAD (2mg/Kg), the CPZ-induced decrease in VFT was significantly cancelled (92.2±4.2% of the initial level). Mitochondria isolated from canine heart after CPZ injection showed a significant decrease in respiratory control index and ADP/O. Effects of CPZ on canine heart mitochondria were also well cancelled by prior administration of FAD. The findings suggest that the arrhythmogenic action of CPZ might be associated in part with impaired function of heart mitochondria. These results also suggest that FAD might be useful in the treatment of the cardiac disturbances associated with overdosage of CPZ

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Specific activities of enzymes in bovine hearts were measured. The enzyme activity ratios between the conduction system and the myocardium were 1.9 for G-6-PDH, 1.2 for PFK, 0.5 for total phosphorylase and LDH, 0.4 for GOT and MDH, 0.3 for SDH, 0.2 for Aldolase and CPK, and 0.1 for αGPDH. Approximate values for relative volume of Purkinje cells, nerve fibers and connective tissues in the conduction system were 30%, 8%, and 62%, respectively. It is concluded that activities of enzymes serving for anaerobic glycolysis in Purkinje cells are almost the same or slightly higher than those in the myocardium, and activity of enzyme for pentose shunt in the conductive tissue is higher than that in the myocardium

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Using cross-sectional echocardiography, left ventricular thrombi were easily found in a 10-year-old boy suffering from congestive heart failure resulting from long-standing endocardial fibroelastosis. Ten days after this procedure, the patient suddenly manifested the signs of acute embolic occlusion of the abdominal aorta and succumbed. Emboli removed from the aorta were histologically confirmed to be organized thrombi. Cross-sectional echocardiography was useful in the antemortem detection of left ventricular thrombi in this pediatric patient

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SHRSP and WK had no angioarchitectural difference. Ring-like fat deposits were detected in the spinal arteries of prehypertensive SHRSP fed on an HFC diet. The predilection sites of ring-like fat deposition were essentially similar to those in the cerebral arteries.

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No effect was observed on cerebrovascular atherogenesis after cervical sympathectomy in renal infarction hypertensive rats. These results suggest that denervation has no effect on atherogenesis in renal infarction hypertensive rats and the role of the nervous system is more important in the development of fat deposition in SHRSP which show greater susceptibility to genetic hypertension and atherogenesis

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When Ca uptake in the presence of ATP is referred to as (active plus passive) Ca transports and Ca uptake in the absence of ATP as passive one in microsomal fractions of SHRSP, there is an inverse effect between (active plus passive) Ca transports and passive transports. At 2 or 3 months old, when the hypertensive stage is remarkably progressing, the active Ca transport is lowered while passive one accelerated. Although this present result seems to be partly inconsistent with the Ca-ATPase activity, inverse relationship on Ca uptake in sarcoplasmic reticulum level is well agreement with the result of Ca effect on tonus of rat aortic strips. This observation on hypertensive development would be of interest in view that this Ca uptake rate has been lowered at 2 or 3 months old when hypertensive stage is progressing

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It was suggested that VCG of 60 day-old WK rats were similar to that of 2-11 month-old human infants in angle and magnitude of the maximum QRS vector, except of the QRS loop rotation in the F plane. In comparison with human adult VCG, it was clear that the direction of the maximum QRS and P vector were deviated to -z direction in the LS and H plane in rats

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(1) In Experiment 2, the deformity or irregularity of QRS vector in VCG was ascertained to correspond to myocardial necrosis and fibrosis
(2) In Experiment 1, myocardial lesions of SHRSP could be detected vectorcardiographically about 1 year of age. And, such myocardial lesions as diffuse fibrosis developed progressively but rather gradually, compared with "sudden onset" of the artificial myocardial infarction as demonstrated in Experiment 2
Thus, vectorcardiographical or pathological study on the heart of SHRSP and its comparison with the surgically induced myocardial infarciton in WK demonstrated that the heart of old SHRSP could be used as the model of myocardial infarction

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The smaller ratio of LV space to the whole sectional area of the heart in Group 6 may correspond to the "concentric" LVH. On the other hand, the delated RV space and the increasing tendency of LV space in Group 8 suggested the morphological process to cardiac failure in old SHRSP, which might be reflected in the predominant prolongation of QRS duration in ECG. The thickening of the coronary arterial wall with narrowed lumen was well correlated to LVH. And, it was detected even at the age of 1 month in the "prehypertensive" state. Therefore, there may be coexisting the predisposition to cardiac hypertrophy as well as to the medial hypertrophy of arterial wall

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1. Although the PRA of substrain B2 was almost the same as that of WK, the PRA of substrain C had significantly low values in comparison with that of them
2. The molecular weights of PR in WK and SHR had almost the same values, but in SHRSP it increased in accordance with elevation in blood pressure
3. Young WK and SHRSP had only small molecular weight renin in the kidneys, but old WK and SHRSP had both big and small ones
4. In kidneys of old SHRSP, the activity of the big molecular weight renin was higher than that of the small one, in contrary of old WK

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Decrease in Δ⁴-reductase activity was observed in SHR at 15 and 20w of age, e.g., only when hypertension was established. Even if hypertension was corrected by fusaric acid (FA) administration, the decrease in Δ⁴-reductase activity was not reversed. Thus the decrease in Δ⁴-reductase in SHR might be caused by factors other than hypertension

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Lower glucose tolerance was observed not only in the hypertensive examinees but also in the normotensives with obvious family history of cerebral stroke, and this was similar to the findings obtained in adult SHR as well as in the prehypertensive SHR, indicating that a minute deviation of glucose metabolism detected by GTT might be related to the genetic desposition to hypertension. Serum cholesterol level was slightly decreased 1 hour after glucose administration both in humans and rats. This response may be the general biological phenomenon showing an intricate relation between glucose and cholesterol metabolisms. GTT is expected to be one of the parameters for predicting hypertension and cerebral stroke clinically and epidemiologically

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1) Effect of modified medium on tonus. The application of high concentration of Ca in medium produced an elevated tonus in SHRSP, but it did not so in WKR. This elevation in SHRSP was larger in 12M SHRSP than in 3M SHRSP. The authors reported that Ca influx was accelerated in SHRSP. These results agree with the previous report. The fact that the elevation of tonus was larger in 12M SHRSP than in 3M SHRSP suggests that the accelerated Ca influx may be more remarkable in 12M SHRSP than in 3M SHRSP. The elevation of tonus by a decrease of Na in medium was larger in SHRSP than in WKR. It was reported that the elevation of tonus by the decrease of Na might be due to Ca influx and Ca release. The fact that the elevation was found in younger SHRSP suggests that Ca influx and Ca release may be accelerated also in younger SHRSP. The fact that the elevation was larger in 12M SHRSP than in 3M SHRSP suggests that the accelerated Ca influx and Ca rlease may be more marked in 12M SHRSP than in 3M SHRSP. 2) Responses to K, NA and Ca. The responses to these contractile agents were larger in SHRSP than in WKR. The authors reported that the contractions by NA and K were due to Ca influx and Ca release. This result suggests that Ca influx and Ca release are more accel-erated in SHRSP compared with WKR. The fact that the contractions by these contractile agents were larger in 12M SHRSP than in 3M SHRSP suggests that the accelerated Ca influx and Ca release are more remarkable in 12M SHRSP than in 3M SHRSP. Immediately after the exchange to Ca-free medium, the contraction by NA was reduced in SHRSP, but that in WKR was not affected. This result suggests that the contraction by NA in SHRSP is due to Ca influx and Ca release, that in WKR being due to Ca release only. By a long time incubation in Ca-free medium, the contraction by NA disappeared in SHRSP and WKR. The disappearance time was shorter in SHRSP than in WKR. This suggests that the release of Ca from Ca store may be accelerated in SHRSP compared with WKR. The disappearance was also faster in 3M SHRSP than in 12M SHRSP. This fact suggests that the Ca content in store may be smaller in younger SHRSP than in older SHRSP

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To find out the cellular role to develop hypertension, the characteristics of membrane systems in vascular smooth muscle to regulate the intracellular Ca²⁺ level were investigated. The differences between Spontaneously Hypertensive Rats (SHR, Okamoto-Aoki) and Kyoto Wistar normotensive rats (KNR) in contractile response and Ca²⁺ influx in the presence and absence of Ca²⁺-antagonist (verapamil) were analyzed. (i) Aortic strip could induce rapid tension by serotonin (5HT) and noradrenaline (NA) in Ca²⁺-free medium but not by K⁺. (ii) SHR aortic strips developed larger tension than KNR in normal physiological salt solution (PSS). (iii) SHR aortic strips developed tension was more inhibited by verapamil than KNR. (iv) Ca²⁺ influx in aortic tissue from SHR was smaller than that from KNR, and verapamil inhibited Ca²⁺ uptake in SHR more greatly than in KNR. These findings suggest that the membrane systems of SHR aortic muscle have an abnormal function

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The cerebral, spinal and mesenteric arteries or arterioles in SHRSP showed fat deposition with high incidence. However, no fat deposition was observed in the retinal arterioles. This dissociation might be due to the difference in the innervation of vessels between cerebral and retinal arteries or arterioles

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The noradrenergic fluorescence at the nerve terminals was augmented during the ontogenic development in the mesenteric arteries, cerebrobasal arteries and renal arteries of SHRSP. The finding suggests that the sympathetic aminergic neuron system may be altered genetically in SHRSP. The nervous system in young SHRSP may accelerate the vasomotion of systemic and cerebral afteries, leading to severe hypertensive vascular lesions observed in adult SHRSP

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