Electrophysiologic study was performed in 25 patients with tachycardia or bradycardia attacks. The coronary sinus (CS) and filtered bipolar esophageal electrograms were recorded simultaneously to compared the phase of atrial activations. During sinus rhythm and high right atrial pacing, the esophageal and proximal CS atrial activations were nearly simultaneous but earlier by 26±5 msec on the average than the distal CS atrial activations. During reciprocating tachycardia due to reentry using a left-side accessory atrioventricular pathway for retrograde conduction the esophageal and CS atrial activations occurred earlier than the low septal right atrial activation, so the esophageal lead can be used as a substitute for the CS lead to clarify the eccentric retrograde atrial activation sequence. By using the filtered bipolar esophageal lead, the interval from Q wave on the surface electrocardiogram to the first rapid deflection on the esophageal atrial activation (Q-A_ESO interval) was measured in 15 patients with supra-ventricular tachycardia. All patients with reciprocating tachycardia due to reentry using a left side accessory atrioventricular pathway had Q-A_ESO intervals between 100 to 130 msec and four of five patients with a right side accessory atrioventricular pathway for retrograde conduction had Q-A_ESO intervals between 130 to 150 msec. In contrast, all patients with reentry in the atrioventricular node had Q-A_ESO intervals between 30 to 60 msec. The esophageal lead is also of value in the prompt diagnosis of atrial flutter and ventricular tachycardia, since the esophageal electrograms readily reveal the relationship between atrial and ventricular activations. In conclusion, the filtered bipolar esophageal lead provides a non-invasive method for the quick diagnosis of various arrhythmias.

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In order to clarify the hemodynamic characteristics in essential hypertension (HT) with angina pectoris (AP), systolic time intervals (STIs) were measured in 13 normal subjects (N), 23 patients with AP, 43 HT (WHO stage I: 13, WHO stage II: 23, WHO stage III: 7) and 19 HT with AP (WHO I: 9, WHO II: 10). The ET/PEP ratio was 2.41±0.24 in N, 2.70±0.34 in AP (p<0.02, vs N), 2.25±0.29 in WHO I, 2.13±0.25 in WHO II (p<0.01, vs N), 1.54±0.37 in WHO III (p<0.001, vs N), 2.68±0.32 in WHO I with AP (p<0.05 vs N: p<0.005, vs HT) and 2.71±0.30 in WHO II with AP (p<0.02, vs N: p<0.001, vs HT). Ejection time index (ETI) was 385±15 msec in N, 399±16 in AP (p<0.05, vs N), 387±13 in WHO I, 385±15 in WHO II, 363±25 in WHO III (p<0.05, vs N), 393±16 in WHO I with AP and 402±15 in WHO II with AP (p<0.05, vs N: p<0.01, vs HT). Pre-ejection period index (PEPI) was 142±10 msec in N, 135±11 in AP, 148±12 in WHO I, 156±13 in WHO II (p<0.005, vs N), 192±24 in WHO III (p<0.001, vs N), 134±13 in WHO I with AP (p<0.05, vs HT) and 136±9 in WHO II with AP (p<0.001, vs HT). These results showed that the ET/PEP ratio in HT with AP was significantly higher than that in HT alone, and this increase in ET/PEP ratio was mainly due to the shortening of PEP interval in WHO stage I and the lengthening of ET in addition to it in WHO stage II. Thus, the changes of STIs in essential hypertension, but identical with those in patients with angina pectoris.

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The effects of nitroglycerin (NTG) on cardiac function can be evaluated by echocardiography. In this paper, we discuss the effects of NTG on cardiac function in two groups of subjects, one with artificial pacemakers implanted with a fixed heart rate, and the other examined as the control group. Left ventricular dimension was obtained in the standard manner using the electronic sector scanning system of Toshiba SSH-11A. Left ventricular end-diastolic and end-systolic dimensions (Dd and Ds) were obtained in each case and the ejection fraction was calculated. After the sublingual administration of NTG (0.6 mg), the blood pressure decreased in both groups. The ventricular rate was fixed in the pacemaker group but increased significantly in the control group. Dd and Ds were found to decrease only in the control group. The ejection fraction showed an increase in the majority of the control group but remained unchanged in the pacemaker group. Heart rate change therefore may play a role in dimensional change and pumping function of heart after NTG.

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Changes of left ventricular (LV) pressure-diameter-velocity relations by alterations in heart rate (HR) were investigated in 6 conscious dogs, instrumented with a pair of ultrasonic crystal probe, a micromanometer in LV and pacing electrodes on the left atrium. By atrial pacing the following four stages of HR were produced: stage (s)-I 112, S-II 134, S-III 158 and S-IV 179 bpm (mean HR). these alterations in HR were repeated before and during acute pressure loadings by methoxamine infusion. LV pressure-diameter and pressure-velocity relations were evaluated by the slope value of LV peak systolic pressure (LVSP)-end-systolic diameter, E(D) max, and by the ratio of changes in mVcf (mean velocity circumferential fiber shortening) and LVSP before and during pressure loading, ΔmVcf/ΔLVSP, respectively. The average of E(D() max at each stage of HR was 9.45, 12.63, 12.59, 11.22 mmHg/mm, and ΔmVcf/ΔLVSP was -0.009, -0.006, -0.007, -0.009 circ./sec.mmHg, respectively. E(D) max increased more at S-II and S-III than at S-I, and reversely, E(D) max increased more at S-IV than at S-II. Similarly, ΔmVcf/ΔLVSP increased more at S-II than at S-I and decreased more at S-IV than at S-II, while ΔLVSP and ΔEDD (end-diastolic diameter) were not different between stages. These changes in E(D) max and ΔmVcf/ΔLVSP presented the mountainous pattern effected by alterations in HR, whose changes were almost similar to that of LV peak positive dp/dt and mVcf before pressure loading. Thus, E(D) max is augmented by an increase in HR, which suggests the Bowditch-effect. Reversely, a decrease in E(D) max at a higher rate indicates a depressed inotropic state. E(D) max id dependent on HR and is a sensitive indicator of the contractility of LV.

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Antistreptococcal esterase (an antibody to extracellular esterase produced by Group A streptococci: ASE) was evaluated according to Hayano's method by using an assay kit on sera of children from two schools, one (F-school) in a non-epidemic state and the other (I-school) in an epidemic state of Group A streptococcal infection. Out of 104 children of F-school, 51 with negative throat cultures for Group A streptococci showed a mean serum ASE titer of 191±144 unit, and 53 with positive throat cultures for Group A streptococci showed a mean serum ASE titer of 360±147 unit. Follow-up determinations on serum antibodies to four Group A streptoccal antigens were performed on the children from I-school during a period of 13 months after an epidemic infection of Group A streptococci. The initially elevated serum ASE titer showed a decreasing trend on subsequent bleedings during the study period as well as antistreptolysin O (ASO) and antideoxy-ribonuclease B(ADN-B) titers. However, the changing pattern of the anit-streptococcal polysaccharide (ASP) titer was different from that of the other three antibodies. A positive correlation was observed statistically between ASE and ASO titers, and also between ASE and ADN-B titers. The ASE tests appear to be useful for serological evidence of a streptococcal infection.

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Streptococcal esterase is known as one of the extracellular products of Group A streptococci. In this paper, an antibody of streptococcal esterase titers in patients with rheumatic fever, acute glomerulonephritis and other streptococcal infections were determined. In cases with acute rheumatic fever and acute glomerulonephritis, ASE titers showed almost the same changes as ASO, ASK and ADN-B. The characteristics of ASE determination, however, is that small changes in the titers could be detected because the final definition of this titer was determined by photometer.

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The distribution of serum antistreptococcal esterase titers in healthy school children, aged 10 to 12, and in healthy adults was determined by the method used by Hayano and Tanaka. The upper limit of its normal titer value was 600 ASE units in the children and 500 ASE units in the adults, and its diagnostic levels were over 600 ASE units in children and over 500 ASE units in adults. There was no close correlation between ASE and ASO or ADN-B.

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Clinical isolates of group A, B, and G streptococci were compared in regard to their extracellular deoxyribonuclease (DNase) activities by the modified assay system for DNase using DNA-methyl green complex as a substrate. DNase activity in a culture supernatant of each strain was measured as a percent decrease in the substrate-specific absorbance at 640 nm. After 1 hr incubation, DNase activities in all the strains of group A streptococci were found to be markedly higher than those of any strain in the other groups, although the DNase activities in groups B and G were considerably heterogeneous. These findings were also seen when commercially available DNA-dye complex reagent for the determination of anti-DNase B antibody titer was used as a substrate in the assay system. Our results suggest that this newly established assay system could be applicable for the rapid measurement of DNase activity to distinguish group A streptococci from the other groups.

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The clinical features of 205 cases of rheumatic heart disease in Bangladesh, including unique two-dimensional echocardiographic findings, were reported, and these were compared with those of 387 Japanese cases. The percentage of mitral stenosis (MS), aortic valvular diseases including both aortic stenosis and aortic regurgitation (A), mitral stenosis with aortic valvular diseases (MS+A) were almost the same between the two countries, but that of mitral regurgitation (MR) was higher, mitral stenosis and regurgitation (MSR) was lower in Bangladesh. The mean age of the patients with mitral valvular diseases was very young and the incidence of atrial fibrillation was very low in Bangladesh. Males predominated over females in MS (male/female= 1.2/1) and the incidence of pulmonary hypertension in MS was higher in Bangladesh. A two-dimensional echocardiographic examination showed that the rough zone was heavily involved in the rheumatic process with having a narrow mitral valve orifice while the clear zone was relatively spared and pliable in many patients with MS in Bangladesh. In MR, posterior mitral leaflets were shortened and made immobile by its submitral complex which were also thickened, fused and shortened, and these resulted in a gap or non-coaptation of the two leaflets in many patients.

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Serum immunoglobulin levels, complement titers, circulating immune complex levels, and chemotaxis of granulocytes were evaluated in 32 patients with Kawasaki disease with or without coronary aneurysm. The group of patients with coronary aneurysm showed relatively higher levels of IgG. Regardless of the presence of coronary aneurysm, the level of IgE in the acute phase was higher than that in the convalescent phase. The level of immune complexes was higher in the group of patients with coronary aneurysm (p<0.05). There was a low negative correlation between immune complexes and CH50. The chemotaxis of the patients with coronary aneurysm was significantly impaired (p<0.01).

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In our previous study, a high rate of "heterophile antibody" was found in idiopathic cardiomyopathy. In the present investigation the cytotoxic activity of this antibody was examined in cultured myocardial cells. Trypsin treated cells cultured for 3 days were used in the two-step method of the complement dependent cytotoxity test. The trypan blue dye-exclusion method was utilized to determine the percentage of surviving cells, and the cytotoxic effect was expressed by the cytotoxic index (CI). With fresh rabbit serum as complement, the mean CI value of the heterophile antibody positive sera was 20.7, which was in contrast to the value of anti-heart antibodies negative sera (p<0.01). As the cytotoxic effect to the heterophile antibody was absent without the complement, it may be complement dependent. Thus, our results suggest that the heterophile antibody may play a role in the pathogenesis or be an incremental factor of idiopathic cardiomyopathy.

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We studied the effects of Coenzyme Q₁₀(CoQ₁₀) on DBA/2 mice inoculated with the M variant of encephalomyocarditis virus. The mice were treated as follows: 1) CoQ group (n=49); CoQ_<10%gt; 1.0 mg (0.1 ml)×2/day (0.1 mg/g/day), 2) control group (n=55); sham-liquid 0.1 ml×2/day. These treatments were intraperitoneally performed every day on days -1 to 12. In both groups, we determined the heart and serum contents of CoQ₎ and CoQ₁₀, which are the biologically active forms of CoQ in mice, in the mice killed on days 3-4 and 7. There was no significant change in the cumulative incidence of myocarditis in both groups. The survival rate was significantly higher on days 5-12 in the CoQ group than in the control group. There were significant increases of CoQ₉ content on days 3-4, and CoQ₁₀ content on days 3-4 and 7, in the heart in the CoQ group as compared with the control group. There was no significant change in the serum content of CoQ₉ in both groups. The marked increase of the serum CoQ₁₀ content seen in the CoQ group was due to the results of exogenous administration of CoQ_<10<. Thus, it may be concluded that CoQ₁₀ may have a protective effect against viral myocarditis in man, in whom CoQ₁₀ is only an active form of CoQ.

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In an attempt to prove that myocarditis may be a cause of idiopathic cardiomyopathy, 10 cases with acute myocarditis were involved in a long-term follow-up study. there were 9 males and 1 female patient, ranging in age from 22 to 63 years. The etiology of myocarditis was idiopathic in 9 cases and rubellavirus in case. clinical findings in the acute stage consisted of congestive heart failure in 6 case, Adams-Stokes syndrome in 2 cases and cardiomegaly in 2 cases. The mean follow-up period was 55 months. Follow-up studies included physical examinations, 12-lead ECG, chest X-rays and two-dimensional echocardiograms. Various patterns of residual ECG abnormalities in the chronic stage were found, such as conduction disturbance in 1 case, pseudoinfarction patter in 4 cases, ST-T changes in 2 cases and premature ventricular contractions in 2 cases. The cardiothoracic ratio of all cases was 60±4% in the acute stage. Two cases (Case1 and 2) died 16 and 36 months after the acute onset, respectively. Four cases had residual cardiomegaly even in the last study period. An echocardiographic follow-up study of 7 cases disclosed progressive left ventricular (LV) dilation and dysfunction in 3 cases, regression of LV dilatation in 2 cases and stable LV function in 2 cases. Two cases out of 3 with progressive LV dilatation and dysfunction expired after the acute illness. It was therefore suggested that acute myocarditis may cause LV dilatation and/or wall hypertrophy and that idiopathic cardiomyopathy may represent the end-stages of previous myocarditis.

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Serial endomyocardial biopsy findings in 20 cases with acute myocarditis of possible viral origin were analyzed. The histopathological findings were analyzed during the acute (0-10 days after the onset: 8.3±1.9 days; 6 cases), the subacute (11-21 days: 18.2±2.2 days, 6 cases), and the convalescent stages (22-167 days: 54.5±45.4 days: 8 cases). The incidence and severity of various changes of the cardiac myocytes and interstitial changes were analyzed and compared at each stage of the disease. In the acute stage, interstitial cell infiltrations were composed of fibroblasts, macrophages and lymphocytes, taken out in descending order. In the convalescent stage, interstitial cell infiltration showed a marked increase and was replaced by fibrocytes. In the subacute stage, transitional changes between the acute and convalescent stages were observable. A controlled myocardium in 21 cases with myocardial infarction which were compared at various stages revealed that in the acute stage, neutrofiles were most prominent, and in the subacute and convalescent stages, macrophages were most prominent and plasma cells were most often observed. The time course changes of the histopathological findings in acute myocarditis were as follows: In the acute stage, 1) Interstitial cell infiltration which is composed of fibroblasts, macrophages and lymphocytes, 2)fragmentation of the muscle bundles, 3) myocytolytic changes, 4) swelling and scarcity of the cytoplasm and swelling of nuclei, 5) variation in size of the myocytes, 6) disarrangement of the muscle bundles, 7) interstitial edema, 8) increased glycogen deposition in the myocytes, 9) abnormal branching of the myocytes, and 10) interstitial fibrosis were observable. In the convalescent stage, most of the above described findings were still observable except for the myocytolytic change, swelling of myocytes and interstitial edema. In the subacute and convalescent stages, an increase in abnormal branching, an increase in double nuclei in the myocytes, and nuclear degeneration were observable. Further control study comparing the change in the convalescent stage of myocarditis and the myocardial changes in cases with chronic right ventricular overload in 58 cases revealed that in the former, fragmentation of the muscle bundles, abnormal branching, size variation, glycogen deposition, and large mononuclear cell infiltrations were significantly more frequent. It is concluded that serial endomyocardial biopsy is useful in assessing the time-course changes of the myocardium in myocarditis.

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In a series of studies with endomyocardial biopsy, 7 adult cases with cardiac disease and eosinophilia were studied clinically and electromicroscopically. Degranulation of the eosinophils in the peripheral blood was observed ultrastructurally in 3 of the cases studied. The clinical expression of the 7 patients were, restrictive cardiomyopathy in 2, dilated cardiomyopathy in 2 and sick sinus syndrome in 1 and others in 2. Endocardial thickening was observed in 5 cases, one of whom showed a marked cellular infiltration with macrophages, plasma, cells, lymphocytes and mast cells. One other case showed cell debris of degranulated eosinophils. Degeneration of the myocytes was manifested by an increase in Z-bands of the myofibrils as well as streaming (1 case), disarrangement of the myofibrils, and mitochondrial change (1 case) which was characterized by giant mitochondria (1 case) as well as by a numerical increase in mitochondria. Increase of atrial granules and mitochondria in a right atrial biopsy of a case with sick sinus syndrome was noteworthy. Basal lamina layering of the capillaries of the myocardium and pyknosis of an edothelian cell cytoplasm were also noted in each case. These observations may reveal that various disease processes are taking place in the endocardium and adjacent myocardium.

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Twenty four-hour ambulatory ECG monitoring were examined in 68 patients (33 patients in a young group and 35 patients in an adult group) with mitral valve prolapse (MVP) in order to characterize the features of arrhythmias in young patients with MVP in comparison with those in adult patients. Diagnosis of MVP was made by two-dimensional echocardiography. On 24-hour ambulatory ECG monitoring 29 patients (88%) in a young group had arrhythmias which was as frequent as those in adult group, but serious ventricular arrhythmias were more often detected in the young group (7 patients) than in the adult group (2 patients). It was considered that arrhythmias in young patients with MVP were frequently serious but accompanied without any symptoms and cardiac dysfunction.

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A long term follow-up study of arrhythmic graduates from junior or senior high schools under the Heart Disease Program in Osaka was performed by mailing questionaires. The age of the total 515 subjects ranged from 20 to 38 years, 26.9 years on an average. From 397 graduates (77%), answers to questionaires were obtained. We could confirm 92 graduates were alive (18% of total subjects) among the 118 graduates who did not return their answers to the questionaires. The following is what we could confirm through the present study: 1) The prognoses of simple premature beats, Wenckebach type heart block and complete right bundle branch block are good in young adults. 2) The prognosis of sick sinus syndrome does not warrant an optimistic prognosis even in young adults. 3) The prognosis of WPW syndrome in young adults is not always fair if they have a history of paroxysmal tachycardia. 4) From 95 to 97% of the graduates with arrhythmia as a whole answered that their daily lives are quite similar to those of healthy people. 5) Attitudes toward daily life and medical checks were also studied.

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One hundred ninety-six children ranging in a age from 4 years to 15 years with premature ventricular contraction (PVC) on a resting electrocardiogram (ECG) underwent exercise tests and 29 of them were found to have significant ventricular arrhythmias. They included 8 patients with 2 PVC's in row, 8 patients with 3-4 PVC's in row, and 13 patients with more than 5 PVC's in row (ventricular tachycardia: VT). These 29 patients were evaluated with exercise tests by two-step exercise ECG(TSE) and by treadmill (TM), and with 24 hour continuous ECG monitoring (Holter monitoring). 141 ECG's 77 TSE's, 77 TM's and 46 Holter monitorings were obtained in total, and the incidence of the each study revealing findings compatible with the final diagnosis was 3%, 15%, 51% and 26%, respectively. For detection of 2 PVC's in row, the sensitivity of TSE and TM was not different, but for picking up 3-4 PVC's in row and VT, TM was significantly superior to TSE. Among the VT patients, there were a few cases in whom neither TM nor Holter monitoring alone was sufficient to confirm the diagnosis. Children with symptoms suggestive of ventricular arrhythmias should be carefully evaluated with a combination of exercise tests and Holter monitoring.

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The relationship between oxygen consumption (VO₂) and heart rate (HR) was studied in 62 male children. Based on clinical evaluation and history, they were divided into three groups, i.e., athlete, ordinary and failed. There was a high linear correlation between HR and VO₂ in each individual. The averaged values of the slope and standard deviations were 2.09±0.189 in the athlete group (n=17), 2.60±0.140 in the ordinary group (n=16) and 3.17±0.591 in the failed group (n=29). The statistical differences were confirmed among the groups (p<0.005). The results suggested that the slope of the HR vs. VO₂ relation was related to an inotropic state of cardiac function. We concluded that the slope was a more suitable and more direct evaluation of cardiac function during exercise. Moreover, the method was non-invasive and safe because it required no potentially hazardous maximum work load for the patients.

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Blood pressure (BP) and left ventricular muscle volume (LVMV) were measured in 408 children and adolescents aged 9-15 years. LVMV was determined by M-mode echocardiography. Lean body weight was approximately calculated using body weight, upper arm circumference and triceps skin fold thickness. Lean-BSA was obtained by substituting lean body weight for body weight in the formula for BSA. subjects were divided into the high and the low BP percentile groups according to their BP percentile values. LVMVI (=LVMV/BSA) and lean-LVMVI (=LVMV/L-BSA) were compared between the two groups. LVMVI and L-LVMVI were larger in the high BP percentile group than in the low one. Regression lines of LVMV to BSA were also compared between the two groups. Regression lines of the high BP percentile group were located in a higher position than those of the low percentile group. These results suggest that LVMV are larger in the high BP percentile group than in the low percentile group even if their BSAs are equal. We concluded that left ventricular hypertrophy has been already initiated in the pre-hypertensive stage of human beings as observed in spontaneously hypertensive rats.

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Frank vectorcardiograms recorded on magnetic tape were analyzed by a computer. The study population was 835 normal children aged from 6 to 16. Magnitudes, angles (azimuth, elevation) of the maximal spatial QRS vector and QRS duration were calculated. The magnitude of maximal spatial QRS vector increased significantly in males compared to those in females at ages 9-10, 11-12 (p<0.01) and 15-16 (p<0.001). Though there was no significant difference of elevation in either sex, azimuth tended to move more anteriorly in females than in males. QRS duration in males became longer with increasing age, while in females at age 15-16, it decreased (p<0.001).

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Frank vectocardiograms recorded from 835 healthy children at age 6-16 were pooled into magnetic tapes and they were analyzed by a computer. The magnitudes of the maximal spatial QRS vector were greater in males than in females at ages 9-10, --+12, (p<0.01) and 15-16 (p<0.001). The elevation showed no significant difference in either sex. The azimuth tended to move more anteriorly in females than in males. The QRS duration in males became longer with increasing age, though in females it decreased at age 15-16 (p<0.01).

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