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Biomedical subjects

T Sawayama

Publications and source records attributed to T Sawayama.

At least 19 recordsLinked to original sources

A novel class of enkephalinase inhibitors containing a C-terminal sulfo group.

A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.

Analgesics

[Possible pathogenesis of giant negative T and negative U waves in hypertrophic cardiomyopathy: a report of two cases].

Giant negative T (GNT) and negative U (NU) waves are electrocardiographic findings which have been frequently observed in hypertrophic cardiomyopathy (HCM). Here we report 2 cases. For the first patient, electrocardiographic and left ventriculographic studies before and after the development of GNT and NU waves and left ventricular high voltage during the follow-up period were performed. For the second patient, electrocardiographic and echocardiographic findings were obtained before and after onset of posterior myocardial infarction. In the first patient, posterior papillary muscle hypertrophy was evident on left ventriculography after appearance of GNT and NU waves. In the second patient, both GNT and NU waves disappeared after posterior myocardial infarction. Two-dimensional echocardiograms demonstrated akinesis in the posterior wall, including the posterior papillary muscle, after 8 weeks of posterior infarction. Therefore, we suggest that apical hypertrophy, especially of the posterior papillary muscle, may play an important role in the pathogenesis of GNT and NU waves in HCM.

Aged

[Long-term follow-up of clinical features and ECG changes in 50 patients with HCM].

We studied the relation of ECG changes during the clinical course in patients with hypertrophic cardiomyopathy (HCM). Fifty patients with HCM were categorized in two groups; 20 patients with, and 30 patients without signs of deterioration of clinical state. The changes between the first and the final ECG were compared in these two groups. The average follow-up period was 7.6 years. Twenty patients with clinical deterioration presented increase in QRS intervals (0.06----0.071 sec, p less than 0.025), decrease in voltage of RV5 (2.81----2.38 sec, p less than 0.025), increase in newly developed abnormal Q waves, and P wave changes. In contrast to these cases, 30 patients without clinical deterioration presented no significant ECG changes. Amplitudes of the negative T wave were unchanged in both groups. We conclude that electrocardiographic observations proved to be useful for predicting clinical features in patients with HCM.

Adolescent

[Autonomic function and severity of hypertrophic cardiomyopathy by power spectrum analysis on heart rate variability].

To examine the relation of autonomic function and severity of hypertrophic cardiomyopathy (HCM) with and without ventricular tachycardia (VT) and poor blood pressure response on Treadmill exercise, 30 patients with HCM and 10 healthy controls were selected. Autonomic function was assessed by heart rate variability (HRV) on 24hr-Holter monitoring. The power spectrum analysis was classified into LF component, HF component and ratio of LF/HF. (1) Night time HF and LF decreased, and LF/HF increased in HCM compared with healthy controls. (2) HF decreased more in HCM with VT. (3) LF/HF also decreased in HCM with poor blood pressure response on exercise. These results suggest that autonomic function may be altered in HCM, and severity of HCM proved to be able to be assessed by power spectrum analysis of HRV.

Autonomic Nervous System

[Effect of heart rate on cardiac hemodynamics in patients with aortic regurgitation].

We evaluated the effects of heart rate on cardiac hemodynamics in 10 patients with aortic regurgitation (AR, mean regurgitant fraction: 64.3%). Cardiac catheterization was performed in all patients, and the hemodynamic parameters were obtained by increasing heart rate (80.100.120.140) using right atrial pacing. Regurgitant fraction and total systemic resistance were improved up to 100/min, but aggravated on further increase in heart rate. Cardiac function curve was remarkably improved up to 100/min, but aggravated on further increase in heart rate. LV end-diastolic pressure-volume relation was moved toward the left lower direction up to 100/min, but toward the left upper direction on further increase in heart rate. Thus, it was concluded that in severe AR, cardiac function was improved up to 100/min, but aggravated on further increase in heart rate.

Aortic Valve Insufficiency

Effect of left ventricular hypertrophy secondary to systemic hypertension on left coronary artery flow dynamics.

STUDY OBJECTIVE: The aim was to clarify the characteristics of the phasic blood velocity pattern and their possible causes in left ventricular hypertrophy secondary to systemic hypertension. DESIGN: Measurements of blood velocities in the left anterior descending coronary artery were made with a 20 MHz Doppler catheter with a top mounted annular crystal. All patients had normal coronary arteriograms. PATIENTS: 23 hypertensive patients [systolic/diastolic pressure: 181(SD 15)/100(4) mm Hg)] with left ventricular hypertrophy, and 13 atypical chest pain patients without left ventricular hypertrophy or any abnormal haemodynamic findings (normal controls) entered the study. MEASUREMENTS AND MAIN RESULTS: The left anterior descending coronary artery blood velocity waveform in pressure overloaded left ventricular hypertrophy was characterised by delayed early diastolic inflow. The diastolic rise time of coronary flow (TDR), ie, the time from the beginning of diastole to peak velocity, was higher in patients with hypertensive left ventricular hypertrophy than in normal controls, at 145(56) v 66(15) ms, p less than 0.001. In patients with hypertensive left ventricular hypertrophy, TDR correlated well with the degree of hypertrophy (r = 0.83, p less than 0.01) and also with peak left ventricular systolic pressure (r = 0.62, p less than 0.01). The coronary flow reserve, calculated from the ratio of the diastolic mean velocity after intracoronary injection of papaverine to the resting flow velocity, decreased with prolongation of TDR (r = 0.58, p less than 0.02). CONCLUSIONS: (1) Impairment of early diastolic coronary arterial inflow is the most remarkable characteristic in pressure overloaded left ventricular hypertrophy; (2) preceding systolic vascular compression and impaired left ventricular relaxation correlate with the delayed early diastolic inflow; (3) the delayed inflow is an important possible cause of the decreased coronary flow reserve in the hypertensive left ventricular hypertrophy.

Adult

[Exercise induced precordial T wave normalization associated with U wave inversion in detection of left anterior descending artery stenosis].

Although normalization of inverted T wave is not an uncommon finding during exercise tests, it's clinical significance is still unclear. Exercise 12-lead electrocardiograms (ECGs) were recorded by using Master's 2-step or ergometer. T wave normalization in the anterior chest leads was found in 20 patients with, and 14 patients without coronary artery disease (CAD). Coronary angiography and/or exercise Tl-201 myocardial imaging were also performed in every patient. Exercise-induced T wave normalization was defined as "inverted T wave at rest becoming upright during exercise". ST segment, T and U wave amplitudes were measured before and immediately after exercise. 1) All of the 20 patients (100%) with CAD demonstrated critical stenosis of the left anterior descending artery (LAD). 2) ST deviation was noted in none of the 14 patients (0%) without CAD, and in only 4 of the 20 patients (20%) with CAD. 3) T wave amplitude increased equally in patients both with and without CAD. 4) Exercise-induced U wave inversion was found in 16 of the 20 patients (80%) with CAD, whereas it was found in only 1 of the 14 patients (7%) without CAD. 5) The sensitivity of "U wave inversion" in detection of LAD stenosis was 80%, and the specificity was 93%. We conclude that exercise-induced T wave normalization associated with U wave inversion in anterior chest leads is highly indicative of the specific presence of critical LAD stenosis.

Adult

[Left ventricular hypertrophy secondary to systemic hypertension: its effect on coronary hemodynamics].

To clarify the characteristics and possible causes of phasic blood velocity patterns in pressure overload hypertrophy, we measured blood flow velocities in the left anterior descending coronary arteries in 16 patients with left ventricular hypertrophy secondary to systemic hypertension. These measurements were made with a 20MHz Doppler catheter. All patients had normal coronary arteriograms. The blood flow velocity patterns were characterized by the decrease in the rise of early diastolic inflow velocity. Prolongation in the time from the onset of diastole to peak velocity (TDPV) correlated with the degree of left ventricular hypertrophy. TDPV was prolonged in proportion to the increase in the peak left ventricular systolic pressure and left ventricular ejection fraction. The flow reserve calculated from the ratio of the diastolic mean velocity after the intracoronary injection of papaverine to the resting flow showed a trend toward the decrease proportional to the prolongation in TDPV due to an increase of wall thickness. In conclusion, preceding systolic vascular compression and systolic vascular strain can be factors causing early diastolic inflow disturbance in left ventricular hypertrophy secondary to hypertension. The decrease of coronary reserve may partially be attributable to the decrease in the rise of early diastolic inflow velocity.

Adult

[Treadmill exercise test in patients with hypertrophic cardiomyopathy with and without coronary artery disease].

We studied whether the treadmill exercise test can discriminate between normal and significant narrowing of coronary arteries in patients with hypertrophic cardiomyopathy (HCM) accompanied with chest pain, and we compared the extent of myocardial ischemia during exercise. Thirty one patients with HCM were divided into two groups; 21 with normal coronary arteries and 11 with significant narrowing of coronary arteries. The treadmill exercise test was carried out in both groups. The following parameters were more frequently seen in the group with coronary stenosis. (1) short treadmill time (338, sec vs 542, p less than 0.05). (2) delta SBP less than or equal to 60 mmHg (delta: end point minus rest, 10 cases vs 12, 0.05 less than p less than 0.1). (3) significant delta ST depression (0.17 mV vs 0.05, p less than 0.05). (4) large delta ST/delta HR (3.3 microV.min/beats vs 0.7). delta ST/delta HR greater than or equal to 2.0 was the most useful for differentiating the two groups, and it was 90% in index both sensitivity and specificity for diagnosis of HCM with significant narrowing of the coronary arteries. It was concluded that treadmill exercise induced more severe myocardial ischemia in patients with HCM who had significant narrowing of the coronary arteries than in patients with HCM who had angiographically normal coronary arteries. The delta ST/delta HR was the most useful index for diagnosis of HCM with significant narrowing of the coronary arteries.

Blood Pressure

Accuracy of 20-MHz Doppler catheter coronary artery velocimetry for measurement of coronary blood flow velocity.

The accuracy of 20-MHz Doppler catheter coronary artery velocimetry (Millar Instruments) was evaluated by model experiments using a turntable and a flow tube. In the turntable experiments, the flow away from the catheter tip (away flow) was significantly lower than that toward the catheter (toward flow), but the measured velocities for both away and toward flows were always lower than the known velocities. Nevertheless, the blood velocities measured at a sampling point 4 mm from the catheter tip showed excellent correlation with the known velocities irrespective of flow direction. The shape of the FFT spectra of the Doppler shift frequency from blood was broadened, and the frequency corresponding to the known velocity was always close to the maximum Doppler shift frequency. We concluded that zero-cross detection of blood velocity by the 20-MHz pulsed Doppler catheter provides a reliable measure for evaluating relative velocity changes, although it underestimates the blood velocity.

Blood Flow Velocity

Spectrum of restrictive cardiomyopathy: report of the national survey in Japan.

This report describes clinical profiles and echocardiographic, hemodynamic, and histologic findings in 26 cases of idiopathic RCM based on the diagnostic criteria of (1) heart failure resulting from a stiff left ventricle, (2) normal LV size and systolic function, (3) absence of LV hypertrophy, and (4) cause or association unknown. There were 14 male and 12 female patients ranging in age from 5 to 63 years. Ten patients died during the mean follow-up period of 145 months, and five died of heart failure after 10 years. Three had a family history of HCM. Thromboembolism was observed in eight. Echocardiograms showed normal LV wall thickness and contraction. Hemodynamic characteristics included elevated biventricular filling pressures and a pulmonary wedge pressure that was usually higher than the right atrial pressure. Equalization of biventricular filling pressures was seen, however, in almost all patients with severe tricuspid regurgitation (seven of eight). The square root sign was seen in 50% in RV diastolic pressure tracings and 28% in LV tracings. This sign was observed in patients with elevated filling pressures. Interstitial fibrosis (22 of 23), endocardial thickening (13 of 23), and myofibrillar hypertrophy (10 of 23) were common histologic findings. Severe myocardial fiber disarray consistent with HCM was seen in four patients.

Adolescent

Angiotensin-converting enzyme inhibitors: synthesis and biological activity of N-substituted tripeptide inhibitors.

A new series of highly potent angiotensin-converting enzyme (ACE) inhibitors, 1-(N2-substituted L-lysyl-gamma-D-glutamyl)octahydro-1H-indole-2-carboxylic acids, was synthesized; various acyl groups were introduced at the alpha-amino group of the N-terminal P1 Lys. The effect of the N2-acyl groups on in vitro inhibitory activity and oral antihypertensive effect was examined. All of the synthesized N-acyl tripeptides were found to have in vitro inhibitory activity at an approximately nanomolar level, and showed antihypertensive potency in renal hypertensive rats at a dose of 10 mg/kg, when administered orally. Among them, compounds 7e, g and 9f, i, m showed potent and long-lasting antihypertensive effects compared with enalapril (2a). Their structure-activity relationships are also discussed.

Angiotensin-Converting Enzyme Inhibitors

[Significance of negative U-waves during anginal attacks: correlation with severity, location and prognosis of coronary stenosis].

Negative U-waves (NU) are not infrequently observed during anginal attacks. Correlations of prevalence of NU and coronary arteriographic findings were observed in 84 patients whose 12-lead electrocardiograms were obtained during anginal attacks. The left anterior descending coronary artery (LAD) was involved in 27 patients, the left circumflex artery (LCX) in 23 and the right coronary artery (RCA) in 34. NU were observed in 44 (52%) of 84 patients with angina; 17 (63%) with LAD, 13 (57%) with LCX, and 14 (41%) with RCA stenosis. The majority (91%) of patients with angina-induced NU had severe (greater than or equal to 90%) coronary stenosis. In the patient group with LAD stenosis, NU were most frequently observed in V4 (59%) greater than V5 (56%) greater than V6 (37%) greater than V3 (33%), while more frequent in V6 (52%) greater than V5 (48%) in the group with LCX stenosis, and in III (29%) greater than a VF (24%) greater than V6 (21%) in the group with RCA stenosis. Thus, the location of the stenosed vessel could be predicted electrocardiographically from the sites of the NU. Coronary revascularization was performed in 10 patients (59%) with LAD stenosis, in nine (69%) with LCX stenosis and in eight (57%) with RCA stenosis. Both anginal attacks and NU resolved after successful coronary revascularization. We concluded that NU proves a highly predictive parameter for detecting and locating significant coronary artery stenosis.

Adult

[A case of acute pericarditis secondary to mediastinitis].

A 45-year-old man who complained of swallowing disturbance and chest pain in inspiration phase was admitted for evaluation of "pericarditis". A chest X-ray film on admission disclosed a wide mediastinal shadow and pleural effusion on the right side. Bilateral tonsils were swollen, and covered with pus. A Computed tomogram of the chest showed a shadow of exudate contained with air in the mediastinum. Mediastinal drainage, tonsillectomy and drainage of fistula from pre-tracheal space to upper mediastinum were immediately performed. Staphylococcus aureus was confirmed from the sputum and mediastinal effusion. Thus, acute mediastinitis was confirmed as an etiological diagnosis of "pericarditis" in this patient.

Acute Disease

[Right pulmonary artery obstruction and pulmonary hypertension secondary to aortitis syndrome].

A 56-year-old woman with aortic arch syndrome and finally right pulmonary artery obstruction secondary to Takayasu's aortitis was presented. She had had a history of visual disturbance and dizziness when she looked upward since 1983. On admission in July, 1984, aortography showed obstruction of the right innominate artery and of the left subclavian artery. Pulmonary arterial pressure, pulmonary perfusion and ventilation images seemed to be normal at that time. After discharge from our hospital, she began in 1987, to be aware of dyspnea on effort. Because of this symptom, she was admitted again in March, 1988. The pulmonary perfusion images showed complete lack of perfusion in the right lung, and arterial blood gas showed hypoxia with 62 mmHg in PaO2, 39 mmHg in PaCO2. Cardiac catheterization confirmed pulmonary hypertension with pulmonary artery pressure of 56/18 mmHg. In conclusion, pulmonary perfusion and ventilation scintigraphy proved to be the best way to clarify the nature of a lesion of the pulmonary artery in aortitis syndrome.

Adult

[Usefulness for evaluation of the left ventricular disorders by apexcardiographic A-wave ratio in patients with hypertrophic cardiomyopathy].

Usefulness for evaluation of left ventricular disorders by apexcardiographic A-wave ratio was studied in 48 patients with hypertrophic cardiomyopathy. These subjects were divided into 3 groups: A-wave ratio less than or equal to 15% (group 1), 16% less than or equal to A-wave ratio less than or equal to 29% (group 2), and A-wave ratio greater than or equal to 30% (group 3). A-wave ratio was found to have a positive correlation with Time constant T (r = + 0.71), left ventricular end-diastolic pressure (r = +0.46), and left ventricular atrial kick (r = +0.55). During exercise, ejection fraction decreased significantly (p less than 0.05) in group 3 as compared to group 1. During treadmill exercise test, rise of systolic blood pressure was significantly (p less than 0.05) poor, and there was a large number of ST depression (p less than 0.05) in group 3. It was recognized by exercise thallium-201 myocardial scintigraphy, that the frequency of perfusion defect was 30% in group 3. In conclusion, high A-wave ratio may strongly suggest impaired left ventricular diastolic function, and, there was correlated to abnormal hemodynamic state during exercise. Apexcardiographic A-wave ratio proved to be useful in patients with hypertrophic cardiomyopathy. It is useful for evaluation of left ventricular disorders.

Adolescent

[A case of silent posterior myocardial ischemia/left circumflex artery obstruction detected by prominent U-wave in right precordial leads].

A 64-year-old woman with a history of hypertension for ten years and of syncope 18 month previously visited our Division of Cardiology on 12 June, 1989. The S4 and mitral regurgitation were audible at the apex, and her electrocardiogram showed ST-depression in leads II, aVF, V5-6 and prominent U-wave (PU) in V1-3 when first seen. Then, she was thought to have a posterior myocardial ischemia. PU in V1-3 diminished whereas T-wave increased after nitrate and Ca++ blocker. Ergometer exercise ECG showed ST-depression in II, III, aVF, V4-6 and PU with decreased T-wave in V2-3 with no apparent symptoms. Simultaneously, Tl-201 myocardial imaging demonstrated a transient posterior defect. A silent posterior myocardial ischemia was, therefore, confirmed. Coronary arteriograms demonstrated subtotal obstruction of the proximal left circumflex artery, and the peripheral site was filled by collaterals from the right coronary artery. Angina-induced PU in the right precordial leads proved to be useful in detection of posterior myocardial ischemia, and this marker may also improve the possibility of detection of silent posterior ischemia.

Coronary Disease