Diurnal rhythm studies were performed on 11 patients with congestive heart failure. Blood samples were taken for the determination of aldosterone, cortisol and plasma renin activity every 4 hours from 12:00 a.m. to 12:00 a.m. the following day. Following this control study, a second diurnal rhythm study was conducted under dexamethasone treatment (0.5 mg of dexamethasone every 4 hours for 48 hours). In the control study, aldosterone and cortisol fluctuated showing a diurnal rhythm with the lowest value in the evening and the highest value in the morning. Plasma renin activity rhythm was indistinct. Fluctuations in plasma renin activity were not parallel with aldosterone. Dexamethasone treatment suppressed cortisol to less than 1 μg/100 ml. Aldosterone values decreased significantly in the morning (p<0.01); this was accompanied by the abolishment of aldosterone rhythm. Plasma renin activity rhythm remained indistinct following administration of dexamethasone. These results suggest that adrenocorticotrophic hormone plays an important role in the control of aldosterone diurnal rhythm in patients with congestive heart failure.

View full abstract

In a series of experimental studies to test the hypothesis that idiopathic cardiomyopathy in man represents a sequela of virus myocarditis, coxsackie B l, 3 or 5 virus was inoculated into ICR mice with two different amounts, that is, a small amount (0.1 ml of 10^5.5 TCID₅₀/ml) and a large amount (0.1 ml of 10^7.5 TCID₅₀/ml). Histopathological and immunofluorescent studies of the heart, analysis of the antibody titers in sera and evaluation of the virus concentration in various organs including the heart were carried out in an acute (up to the 21st day) and chronic phase (up to the 18th month) of the experiment. A small amount of coxsackie B 1 or 5 virus did not cause myocarditis, while a large amount of either virus rarely induced mild myo-carditis. A small amount of coxsackie B 3 virus frequently caused mild myo-carditis without obvious residual pathologic changes of the heart, while a large amount of the same virus always caused acute and severe myocarditis. In these animals, acute myocardial changes are almost in agreement with those in previous investigations except for capillary thrombi. The virus was isolated from the heart with higher titers than from other organs and identified in some cardiocytes by immunofluorescent study until the 14th day. Neutralizing antibody in sera appeared on the 7th day and remained for several months. Approximately two thirds of these mice left no significant myocardial lesions, whereas about one third of them which probably had extensive myocardial lesions in the acute phase developed significant myocardial fibrosis with calcification in the chronic phase. These lesions appeared to become larger after the 6th month. In and around the fibrotic lesions atrophy, hypertrophy and/or disarray of myocardial fibers were observed. These hearts did not show hypertrophy or dilatation but their histologic findings resembled those seen in some cases of congestive cardiomyopathy except for severe calcification in the myocardium.

View full abstract

A 22-year-old man with myotonic dystrophy associated with sick sinus syndrome is described. The patient showed marked weakness of grasping power, grip myotonia, percussion myotonia, bilateral cataracts, fixed facial expression and elevation of serum CPK level, and was diagnosed as having myotonic dystrophy. The Holter ECG showed marked sinus bradyarrhythmia at the rate of 25 beats per minute and the sinus node recovery time using overdrive suppression test was significantly prolonged. These findings indicated the patient also suffered from the sick sinus syndrome. Although various kinds of ECG abnormalities have been noted In the cases with myotonic dystrophy, there have been very few descriptions concerning the involvement of sinus node dysfunction in this disorder.

View full abstract

Clinic blood pressures measured at clinic by physician were higher than home blood pressures measured at home by patients in the majority of untreated patients with essential hypertension, but equivalent or lower in some patients. Clinic minus home blood pressure (ΔP) were correlated with the levels of clinic blood pressure (r = 0.51, p<0.005 for systolic; r = 0.35, p<0.02 for diastolic blood pressure, respectively). The systolic ΔP might be greater in the middle-aged women, especially in the fifties of females than the age-matched males (p<0.05). The ΔP could not be altered by any antihypertensive drugs with the exception of systolic ΔP with diuretic alone. The blood pressure tended to remain more stable throughout the 24-hour period in proportion as the severity of hypertension increased. The observation of circadian variation in blood pressure disclosed that the blood pressure was lower in the morning, but increased gradually, resulting in the relatively high blood pressure between the afternoon and evening in the low renin and volume expanded type of hypertension. On the contrary, the blood pressure was already high in the early morning in hypertensive patients characterized by the accelerated renin-angiotensin system and contracted volume factor.

View full abstract

The subjects included in the present study were 141 hospitalized patients with essential hypertension (EH) and 45 patients with EH complicated with apoplexy and myocardial infarction. Of the former, 15 underwent a 24-hour measurement of direct arterial pressure under unrestricted conditions, and 45 were examined for functioning of the carotid sinus reflex. (1) Even among the hospitalized patients with EH, blood pressure (BP) showed large diurnal variations. Falls and spontaneous fluctuations in BP were observed at a time during nocturnal sleep. The lowest BP (the "dale" pressure) observed at that time remained almost unchanged throughout the night (S.D. &les;6 mmHg) for each patient. Since casual BP varies considerably during a day, other laboratory findings should also be taken into account for evaluation prior to initiating antihypertensive treatment. (2) The 186 patients with EH were classified by multivariate statistical analyses of laboratory findings into 4 clusters (types). Then, a new severity index was made in order to evaluate atherosclerotic and hypertensive changes in each patient. (3) A newly devised carotid sinus stimulator was used to enhance the distensibility of the carotid sinus. A decrease in systolic blood pressure (ΔSBP) was observed after stimulation although differences in ΔSBP were found between the 4 clusters. There was a positive correlation between ΔSBP and the elastic modulus of the common carotid artery (r = 0.55, P<0.01 ). (4) Each cluster was characterized by differences in plasma renin activity and cardiovascular abnormalities. This classification is considered to be useful for the antihypertensive treatment.

View full abstract

Diurnal variations of the basal blood pressure in patients with essential hypertension were investigated by the indirect recording method. To estimate the reduction in blood pressure at midnight, disturbance of sleep in the patients should be considered. Relationship between neurohumoral factors and the diurnal blood pressure variations were also evaluated. 1) Variations of the casual blood pressure at the clinic visits may be stabilized beyond 15 minutes of the sitting rest. 2) During the out-patient treatment of essential hypertension with placebo for 6 weeks, 16% of the patients showed reduction in mean arterial pressure of 13 mmHg or more. 3) Significant influence of seasons on blood pressure was not apparent for 6 weeks of the placebo treatment of hypertension. But in patients under the long-term antihypertensive treatment, blood pressure in summer was maintained significantly lower than in winter. 4) Self-monitoring of blood pressure by patients at home is valuable for estimating diurnal changes of blood pressure with the antihypertensive treatment.

View full abstract

To confirm our previous study and to observe the effect of long-term antihypertensive therapy, we studied 89 patients with essential hypertension under the following 3 different dietary salt balance conditions: Phase I (control diet); daily dietary salt ingestion of 10 g for more than 10 days, Phase II (low-salt diet); 2 g of salt for 4 days plus oral administration of 120 mg of furosemide on the morning of the first day and Phase III (high-salt diet); 22 g of salt for 4 days. The patients were divided into three groups according to blood pressure response to sodium: Group I (salt-sensitive); mean blood pressure (MBP) in Phase II decreased more than 10% of that in Phase I or that in Phase III exceeded by 10% or more than that in phase II, Group II (paradoxically salt-sensitive); MBP in Phase II increased more than that in Phase I, and the remaining Group III (non-salt-sensitive). Thirty-four, 18 and 37 patients could be classed into Groups I, II and III, respectively. Cardiovascular profiles of the patients on admission did not differ among the three groups except for hematocrit. As compared with MBP on admission, the fall of MBP in Phase I was greater in Group II than in Group I. Percent changes of pulse rate, body weight and hematocrit showed a tendency toward a greater fluctuation in Group I than in Group II, in all three phases. Plasma renin activity and plasma aldosterone concentration among the three groups did not differ significantly in any phase. However, pressure-renin index showed a significant difference between Groups I and II. Antihypertensive drugs given to Group I were all diuretics alone or diuretics plus other(s), whereas in Group 11 there were no patients taking diuretics alone. These results indicate that volume factor(s) contribute to high blood pressure in Group I and vasoconstrictive factor(s) such as renin-angiotensin and sympathetic nervous systems in Group II.

View full abstract

In order to obtain further information on the fundamental relationship between the pathophysiology and the treatment of hypertension, the following variables were measured; plasma volume (PV), extracellular fluid volume (ECFV), total exchangeable sodium (Nae), plasma renin activity (PRA), plasma concentration (pNA) and twenty-four hour urinary excretion of noradrenaline (uNA) together with pressor response to infusion of 0.3 μg/kg/min of noradrenaline (NA response) in patients with uncomplicated essential hypertension. Immediately after admission, supine pNA was positively correlated with diastolic blood pressure (DBP; r = 0.396, p<0.005) and with mean arterial pressure (MAP; r = 0.293, p<0.05) in all hypertensive patients. This correlation was most outstanding in young patients (under 40 years of age; r = 0.752, p<0.01 ), or less but was still significant in the middle aged group (from 40 to 59 years; r = 0.477, p<0.05) and not significant in the older group (over 60 years old). On the other hand, significantly higher pNA and lower PV, ECFV and Nae were observed in patients with normal PRA (NRH) as compared with low PRA (LRH), whereas a remarkable relationship was observed positively between pNA and DBP (r = 0.405, p<0.02) and negatively between PV (r= -0.444, p<0.02), ECFV (r = -0.544, p<0.01) or Nae (r= -0.601, p <0.01 ) and MAP in NRH, but not in LRH. Following two weeks of rest, with a regular diet (Na 256-300 mEq, K 75 mEq), after admission, MAP and uNA decreased and PV, Nae and NA response increased significantly. The reductions of MAP following 2 weeks of rest were significantly correlated with values in pNA and uNA immediately after admission and with the decreases of uNA following 2 weeks of rest. After 2 weeks of rest, a significantly positive orrelation was observed which was more marked in LRH than NRH, between MAP and PV, ECFV or Nae, while no relationship could be detected between MAP and pNA. Following one week of sodium restriction (Na 35, K 75 mEq), MAP, PV and NA response decreased, and pNA and PRA increased significantly. And, following 4 weeks of sodium restriction, a significantly positive correlation was found between the changes in MAP and those in PV (r = 0.7 1 9, p<0.01 ) or Nae (r = 0.686, p<0.025). Following 2 weeks of sodium loading (Na 390, K 75 mEq), MAP, PV, Nae and NA response increased, whereas uNA and PRA decreased significantly. The elevation of MAP in LRH was significantly greater than that in NRH. These findings suggest that in patients with uncomplicated essential hypertension, the enhancement of sympathetic nerve activity may play an important role in maintaining the level of blood pressure, particularly, in younger patients or in patients with NRH or HRH. On the other hand, the role of volume factors may be quite important in hypertensive mechanisms in older patients or in LRH. Therefore, as the antihypertensive treatment, a definite release of physical and mental stress, beta-blockade or sympatholytic drugs should be chosen as an adequate treatment in the former, and sodium restriction or diuretic agents should be selected in the latter.

View full abstract

The effectiveness of diuretic and β-blockers was analyzed in relation to pretreatment plasma renin activity (PRA), plasma volume (PV) and patient's age in mild to moderate essential hypertension. Following results were obtained. 1) Diuretic was more effective in patients with low and normal PRA, high and normal PV, and elderly age, compared to patients with high PRA, low PV, and juvenile age, respectively. 2) Effect of β-blockers (pindolol and oxprenolol) was not different among PRA and PV subclasses. It was more effective in juvenile patients, especially younger than 35 years old compared with elderly patients. 3) In patients with low and normal PRA or with high and normal PV, and in elderly patients, diuretic was more effective than β-blockers. 4) In juvenile patients β-blockers were more effective than diuretic.

View full abstract

The clinicopathological study on the atherosclerosis and cerebrovascular and cardiac complications was carried out in 1561 consecutive autopsied cases in the elderly. The subjects were classified into 3 groups: 702 cases (45.0%) of normotension, 276 cases (17.7%) of systolic hypertension and 583 cases (37.3%) of diastolic hypertension. The acceleration of atherosclerosis by hypertension was prominent in sixties and seventies, less remarkable in eighties and almost none in nineties. The effect of hypertension was remarkable on cerebral artery, aorta and coronary artery in this order, and no difference was found between the systolic and diastolic hypertension groups. On the basis of atherosclerotic changes, strokes and myocardial infarction were prevalent in both these groups in comparison with the normotension group. The difference between the systolic and diastolic hypertension groups and the normotension group was prominent in sixties and seventies, but in eighties only the diastolic hypertension group showed a significant difference with the normotension group. The effect of hypertension was more remarkable on strokes than myocardial infarction. The lack of remarkable effect of hypertension on the cases over eighty may be attributed to the progression of atherosclerosis with age in normotensive cases. The 4 year prospective trial on the effectiveness of the antihypertensive treatment was performed in 100 mild hypertensive patients of the aged, averaging 76.1 years. The matched pair group was selected by the age, sex and blood pressure. Cerebrovascular and cardiac complications were observed in 4 cases or 10.5% of 38 cases of the drug group, and in 9 cases or 22.0% of 41 cases of the placebo group. When the elevation of blood pressure over 200/110 mmHg, observed in 8 cases in the placebo group, were included as one of the cardiovascular complications, the complications in placebo group reached 41 .5%, showing a significant differnce. Other complications such as cancers, infections and bone or joint diseases, were observed in 12 cases or 31.6% in the drug group and in 17 cases or 41.5% in the placebo group. Blood pressure was decreased form 171/87 to 151/80 in the drug group in the 4 year period. The present study suggested that antihypertensive treatment was effective in the aged hypertension, and careful follow up was needed not only for cardiovascular complications but also for general health condition.

View full abstract

Forty seven patients with advanced or malignant hypertension were divided into renin dependent and independent groups based on the response to angiotensin II antagonist, and then hypotensive effectiveness of several kinds of antihypertensive drugs were evaluated in each group. Twenty nine patients were treated principally with propranolol and furosemide. Fifteen out of them were found to respond to angiotensin II antagonist and classified into the renin dependent group, and the remaining 14 patients were non-responders and classified into the renin independent group. Most responders were patients with essential hypertension, while the half of the non-responders were patients with chronic glomerulonephritis. The main difference between the responders and the non-responders was in the level of plasma renin activity, that is, it was higher in the former than in the latter. The responders were treated principally with propranolol. Two thirds of them were treated successfully with combination of propranolol and either furosemide, clonidine or hydralazine. However, the remaining 5 patients were resistant to these combination therapies. On the contrary, in patients with renin independent hypertension, the treatment with furosemide was effective, especially when combined with propranolol, clonidine or other, drugs. Both nifedipine and captopril were useful in the treatment of advanced hypertension irrespective of renin dependency. Hypotensive effects of these antihypertensive drugs were enhanced by the combination with other drugs, especially when nifedipine was administered together with propranolol or clonidine and when captopril was accompanied by furosemide. However, the antihypertensive effect of captopril was found to be attenuated by the addition of indomethacin in a patient with low renin hypertension. These data show that angiotensin II antagonist is useful to predict the effectiveness of antihypertensive drugs in the treatment of advanced or malignant hypertension. Both nifedipine and captopril are very effective irrespective of renin dependency, but it must be noted that the hypotensive effect of captopril is attenuated by the additional administration of nonsteroidal anti-innammatory drugs.

View full abstract

Nifedipine, the Ca⁺⁺ antagonistic coronary vasodilator, was administered by oral, sublingual and enema routes. 1) In 6 severe hypertensive patients (systolic pressure &ges; 200 mmHg, diastolic &ges;120 mmHg), nifedipine, administered orally, induced prompt and reliable fall of arterial pressure (systolic pressure: -28% of control level, diastolic: -27%). 2) In 10 patients with hypertensive emergencies, including malignant hypertension, intracranial bleeding, hypertensive encephalopathy and acute hypertensive heart failure, sublingual and enema administration of nifedipine were performed with excellent hypotensive efficacy. 3) Pressure begun to fall within 5-15 min, 30 min and 30-60 min after sublingual (or dissolved), enema and oral (capsule), respectively, and reached its lowest levels in the next 10-20 min. The fall of pressure lasts for 2-4 hours. 4) In the combination of nifedipine with alpha-methyldopa, antihypertensive response in short-term was increased about +11% over nifedipine alone and lasted for 8 hours. In combination with beta-blocker (propranolol), hypotensive efficacy increased +39% over nifedipine alone, but the effective duration of this combination was the same as nifedipine alone. 5) Side effects, including dryness of the mouth and burning sensation in face and legs, were observed in few patients.

View full abstract