To open up the possibility of exact clinical diagnoses of chronic cor pulmonale, we performed thallium-201 myocardial perfusion scintigraphy on patients with chronic pulmonary disease. From the thallium activity in the left ventricle (plus ventricular septum) and right ventricle counted scintigraphically, we determined the thallium activity ratio of left to right ventricle (TAR). The intra- and inter-observer variations of this ratio were negligible. We compared TAR with pulmonary hemodynamic findings and with left to right ventricular mass ratio measured at autopsy, and obtained the following results. 1) Left to right ventricular mass ratio determined in 11 autopsied patients by the method of Fulton et al. was closely correlated with TAR values (r = 0.90, p<0.001). 2) In patients with chronic pulmonary disease, there were highly significant exponential inverse correlations between TAR and pulmonary arterial mean pressure, total pulmonary vascular resistance and right ventricular systolic pressure with the coefficients of -0.75, -0.72 or -0.77, respectively (p<0.001). These results suggested the possibility that the severity of pulmonary circulatory disturbance may be ascertained non-invasively by TAR measurement. Thus, thallium-201 myocardiai perfusion scintigraphy is able to reveal non-invasively right ventricular hypertrophy in patients with chronic pulmonary disease, and it might be a useful means of clinically diagnosing chronic cor pulmonale. If TAR obtained from scintigrams is smaller than 2, the patient concerned may possibly have right ventricular hypertrophy and he or she may be diagnosed as having chronic cor pulmonale.

View full abstract

To elucidate the hemodynamics and mechanical properties of the myocardium in hypertrophic (HCM) and congestive cardiomyopathies (CCM), preload (end-diastolic stress), afterload (mid-systolic stress), contractility (peak positive dp/dt, (dp/dt)/DP₄₀, ejection fraction), relaxation (peak negative dp/dt, time constant T), compliance (elastic stiffness constant, end-diastolic elastic stiffness), and performance (left ventricular minute work, left ventricular minute work/muscle mass) were determined in 19 patients with HCM, 11 with CCM, and 15 normal subjects. Preload was in the normal range in HCM even with elevated left ventricular end-diastolic pressure. In cases of CCM it was high only when congesive heart failure was present. Afterload was mildly elevated in CCM with heart failure, but only half the normal value in patients with HCM. The three indices of contractility were in the normal range in patients with HCM, and markedly reduced in those with CCM. Relaxation abnormalities were demonstrated in both HCM and CCM. The elastic stiffness constant was high in HCM and normal in CCM. End-diastolic stiffness was normal in HCM and high in CCM with heart failure. These observations suggest that chamber stiffness is markedly elevated in HCM, and stiffness of unit muscle is elevated in CCM when heart failure appears. Although left ventricular minute work was normal in HCM, minute work of unit muscle (left ventricular minute work/muscle mass) was markedly reduced. These observations indicate that the chief problem in CCM is contractile failure and that elevation of preload and muscle stiffness is associated with congestive heart failure in this disease. Although the conventional indices of contractility are in the normal range in HCM, the contractility of unit muscle is reduced, and hypertrophy seems to be a compensatory mechanism when the relations between afterload and ejection fraction and between preload and performance are considered.

View full abstract

The time courses of mean blood pressure (MBP), plasma renin activity (PRA), plasma aldosterone (PA), serum prostaglandin E (PGE), serum angiotensin I converting enzyme (ACE), and blood levels of angiotensin I converting enzyme inhibitor (SQ 14, 225) (captopril) were studied in 6 patients with essential hypertension (5 men and I woman, aged 44 ± 5.6 (mean ± S.E.) years) before and 30, 60, 120 and 180 min after administration of 25 mg captopril, MBP and ACE began to fall within 30 min and reached a significant mini-mum between 60 and 180 min after captopril administration. PRA was significantly increased 60 min after captopril administration and continued for 180 min. On the other hand, PA had begun to fall significantly 180 min after captopril administration. The blood levels of captopril were significantly increased 30 min after captopril administration, with a peak at 120 min. The levels at 180 min were half the peak. The levels of PGE were not significantly changed within 180 min after captopril administration. These results suggest a discrepancy between the changes in MBP and the blood levels of captopril. The blood pressure lowering effect may be due to inhibition of angiotensin II (Ang. II) during the short-acting effect, and due to decrease of PA, metabolites of captopril, increase of kinin in the blood, inhibition of the slow pressor effect of Ang. II, increases of other depressor hormones such as prostacyclin and other depressor mechanisms during the long-acting effect.

View full abstract

Despite recent remarkable developments in computed tomography (CT) for many organs in the human body, its clinical application concerning the cardiovascular system has been slow. In this study, we investigated clinical applications of CT for the cardiovascular system. We used conventional CT without ECG synchronization and ECG-synchronized CT. By the former, the size, the shape, and the arrangement of cardiovascular structures and the presence of pericardial effusion and calcifications were shown. For the latter, ECG gating method and data sorting method were used, and the cardiac border movement, the sequential changes of cross-sectional cardiac areas and the changing ratio were studied by both methods. The cardiac CT was found to be a useful noninvasive method for observation of anatomical features in various cardiovascular diseases and for the analysis of cardiac motion - especially, dyssynergia such as hypokinesis, akinesis and paradoxical movement in myocardial infarctions.

View full abstract

A new method for measuring the opening angle of Bjok-Shiley valve (B-S valve) was reported in 1977. However, this method is complicated enough to permit quick calculation of the opening angle in multiple frames of one cine-film. We devised a new method with using two computers (NAC Cardias GP 2000, TEXAS TI-59) for calculating the opening angle of the B-S valve. We measured the opening angle of 7 cases (they were all implanted B-S valves, 5 were mitral and 2 were aortic). Results are the following: (1) The maximum opening angle ranged from 54 degrees to 65 degrees and the mean value was 58.1 degrees. (2) We showed the floating phenomenon of B-S valve with our method. (3) We showed the accuracy of our method by measuring 10 times the same photograph of B-S valve. (4) We showed that our method is very accurate by comparing the values calculated by our method with those calculated directly from the valve which was removed from a patient. (5) It takes less than 30 minutes to calculate the opening angle of 60 frames (we took 60 frames of cine-film per minutes).

View full abstract

The effects of ouabain on passive electrical properties of isolated rabbit atrial muscle fibers (crista-terminalis) were investigated. The space constant as well as the time constant of the crista-terminalis was determined using the partition method of Kamiyama and Matsuda based on the cable equation pro-posed by Hodgkin and Rushton. Ouabain treatment for 30 minutes at a lower concentration (2 × 10^-7M), caused no significant change in the space constant and time constant of the crista-terminalis. After ouabain treatment for 30 minutes at a higher concentration (1 × 10<-6>M), the space constant of the crista-terminalis was reduced significantly, whereas the time constant was not affected. An apparent reduction in the resting membrane potential and in the amplitude of action potential was also observed at the higher concentration of ouabain. These effects of ouabain on passive electrical properties of the crista-terminalis are most likely explained by the increase of its axial resistance (electrical uncoupling) due to intracellular calcium accumulation resulting from inhibition of the membrane sodium pump. This suggests that such an electrical uncoupling may play an important role in the intra-atrial conduction disturbance by cardiac glycosides.

View full abstract

The distal right ventricular conducting tissues of 45 canine hearts were experimentally interrupted in various degrees by a transmural incision of the right ventricular free wall, a trans-section of the lateral branches of the right bundle or by injury to the endocardial Purkinje network. Right ventriculotomy caused a slight activation delay (less than 10 msec) of the right ventricle which was restricted to the distal area from the incision, but the delay was not long enough to cause a significant prolongation of the QRS duration in the limb lead ECG. In one experiment, a vertical incision in the middle region induced an exceptional, marked alteration of the right ventricular activation sequence and an apparent prolongation of the QRS duration (16 msec) indicating an incomplete RBBB. However, anatomical analysis revealed that the lateral branches were nearly completely interrupted by the incision. An extensive injury to the Purkinje network extending toward the right ventricular outflow tract by a blunt scalpel caused a local activation delay in the outflow tract, without producing any serious delay resulting in an ECG pattern of RBBB. These results may suggest that right ventriculotomy would induce the RBBB pattern of ECG if lateral branches are extensively injured by the surgical procedure, and that the injury to the Purkinje network extending toward the outflow tract does not play a primary role of genesis of RBBB pattern in ECG.

View full abstract

The cholesterol metabolism of a newly established model for atherogenesis, named arteriolipidosis-prone rats (ALR), selected from spontaneously hypertensive rats (SHR), was investigated in comparison with a substrain of SHR (B) (nonarteriolipidosis-prone rats) and the normotensive control, Wistar-Kyoto (WK) rats. Serum cholesterol of ALR was significantly lower than that of WK. Uptake of labelled serum cholesterol by the isolated liver cells at 37°C was higher in ALR than in WK. The data for SHR (B) fell in between these two. On the other hand, on feeding a cholesterol diet, serum cholesterol increased in the order WK, SHR (B) and ALR, with the highest being ALR. The absorption of cholesterol in ALR was about twice as great as in WK and SHR (B).

View full abstract

The effects of angiotensin II, thyroxine and 17β estradiol on plasma renin substrate concentration in rats and renin substrate production by perfused rat livers were investigated. The addition of angiotensin II (1-10μg) to the perfusion system did not affect the synthesis of renin substrate. After treatment with thyroxine (2.5 mg/kg/day), plasma renin substrate concentration, plasma renin activity, plasma aldosterone concentration and the rate of renin substrate synthesis were all significantly increased. 17β estradiol (2 mg) raised both plasma renin substrate concentration and the amount of renin substrate production by the liver. Isoelectric focusing profiles of renin substrate of liver perfusate and of plasma from estrogen-treated rats were different from that of liver perfusate from normal rats. But the profile of renin substrate in plasma was essentially similar to those in liver perfusates both in normal and estrogen-treated rats.

View full abstract

Tonin was purified from rat submaxillary gland homogenates by affinity chromatography on soybean trysin inhibitor coupled CH-Sepharose 4B and two additional steps of conventional chromatography. The use of affinity chromatography by soybean trypsin inhibitor coupled CH-Sepharose 4B permits a new approach in the purification of tonin, since it can completely separate in one step troublesome contamination of the enzymes which showed tosyl-L-arginine methyl ester hydrochloride esterase activity. Tonin is purified 11-fold to a homogeneous state on polyacrylamide gel electrophoresis at a yield of 21%.

View full abstract

Recently, we established a very sensitive, specific and simple direct radio-immunoassay method for human urinary kallikrein. In this study, in order to clarify whether or not the low or high excretion rate of urinary kallikrein activity in patients with essential hypertension, primary aldosteronism, pheo-chromocytoma and Bartter's syndrome is caused by changes in enzyme quantity, urinary kallikrein excretion was measured with this direct radio-immunoassay method in normal subjects and in patients with these diseases. Urinary kallikrein excretion measured as enzyme quantity was significantly lower in patients with essential hypertension, and higher in patients with primary aldosteronism and Bartter's syndrome. These results are consistent with other previously reported data and our data measured by means of esterase assay or kininogenase assay. The results also suggest that lowered or elevated excretion of urinary kallikrein activity in these diseases is caused, in part at least, by the lowered or elevated excretion of enzyme quantity.

View full abstract

The present study shows that there is a circadian variation in the excretion of urinary kinin, kallikrein and prostaglandin E (PGE) as well as urine flow, urinary sodium excretion and urinary potassium excretion in recumbent healthy volunteers. The present data, that the acrophase of urinary kallikrein excretion was 1.5 hr later than that of plasma aldosterone concentration (PAC) and that a significant positive correlation was found in circadian variations between urinary kallikrein and PAC, suggest that the circadian variation of urinary kallikrein excretion may be regulated by aldosterone. The pattern of circadian variation of average urinary kinin excretion coincided with those of average urine flow, urinary sodium excretion and urinary PGE excretion, suggesting that renal kinin and PGE may be involved in the regulation of waterodium excretion. The present data that the phase of circadian variation of urinary kinin was delayed from that of urinary kallikrein and that there was a mirror image between the circadian variation in urinary kinin and kallikrein suggest that there may be a feedback mechanism in renal kallikrein-kinin system.

View full abstract

Cardiac β-adrenoceptors were studied in membrane fractions from spontaneously hypertensive rats (SHR) and rats with two-kidney, one clip hypertension (2K, 1C HT), using radioligand binding method. β-Adrenoceptor concentration measured by [³H]-dihydroalprenolol (DHA) binding was significantly lower in cardiac membranes from two months old SHR than those from Wistar-Kyoto rats (WKY) (38.2 ± 2.6 vs 45.1 ± 1.8 fmol/mg protein, means ± SEM, p<0.05). Cardiac membranes from 2K, 1C HT rats had also a lower concentration of β-adrenoceptors than those from the sham-operated control rats at a week after operation (30.9 ± 2.2 vs 47.8 ± 1.6 fmol/mg protein, p<0.01). But receptor affinity remained unchanged. These reduced concentrations of β-adrenoceptors were restored to control levels at 12 months old in SHR and at 6 weeks after operation in 2K, 1C HT rats, although age-dependent decrease in β-adrenoceptor was observed. The decrease in β-adrenoceptor was associated with increase in plasma noradrenaline levels during the earlier stages of hypertension. But there is no correlation between β-adrenoceptor concentrations and plasma noradrenaline levels in the chronic stages of hypertension. No significant difference was found in activities of 5'-nucleotidase, which is a marker enzyme of cell membrane, in membrane fractions between the hypertensive hearts and the controls, suggesting that the cardiac hypertrophy is not a determinant factor for change in β-adrenoceptor. The observed decrease in β-adrenoceptor concentration may reflect an increase in sympathetic nerve avtivity during development of hypertension. In the chronic stages of hypertension, additional factors may be involved in the restoration of β-adrenoceptors.

View full abstract

To clarify a role of brain angiotensin II receptor binding in development of hypertension, the regional distribution and extent of specific angiotensin II binding were studied in salt-loaded normotensive (NTR) and spontaneously hypertensive (SHR) rats, and Goldblatt one-kidney hypertensive rat (GB). Further, angiotensin-converting enzyme activity was measured in these rats' brains. In control rats, angiotensin II receptor binding was consistently lower in the thalamus, hypothalamus, midbrain, striatum and cortex of SHR rats than in NTR rats. In GB rats, the binding capacity in the thalamus was greater than that of NTR rats. Sodium intake resulted in a rise in the receptor binding capacity in the hypothalamus, thalamus and striatum of SHR rat, whereas it did in a fall in the binding capacity in the hypothalamus, thalamus, striatum, midbrain and cortex of NTR rats. Angiotensin-converting enzyme activity was significantly elevated in the midbrain of salt-loaded SHR rats.

View full abstract

The further role of vasopressin in the pathogenesis of hypertension was studied in two different types of hypertensive rats in which the intravenous injection of a vasopressin antiserum reduced arterial blood pressure substantially. The increased secretion of vasopressin was demonstrated in deoxycorticosterone acetate (DOCA)-salt hypertensive and spontaneously hypertensive rats with high salt intake. Angiotensin II binding of the brain receptor which has been postulated to modify osmotically stimulated vasopressin release from neurohypophysis was not affected by sodium balance in these types of hypertensive rats, whereas the decrease in the brain receptor binding of angiotensin II was observed in the control rats. The lack of the adjusting control system in the brain angiotensin II receptors for sodium balance may be, at least in a part, responsible for the enhancement of vasopressin secretion in the hypertensive rats compared to that in the control rats with high salt intake. Since pressor responsiveness to vasopressin was increased in the rats with DOCA-salt hypertension, vasopressin may function as a direct pressor agent in the maintenance of high blood pressure in this type of hypertension.

View full abstract

To investigate the role of the central and peripheral dopaminergic systems in the control of the renin-angiotensin-aldosterone system in conscious rats, dopamine or its antagonist, metoclopramide, was injected intravenously (i.v.) and intracerebroventricularly (i.c.v.). Dopamine (100 μg/kg), when injected i.c.v., decreased plasma renin activity (PRA) and plasma aldosterone concentration (PA), while metoclopramide (50 μg/kg, i.c.v.) increased both of them. Intravenous administration of dopamine (1 μg/kg/min) did not produce significant changes in either PRA or PA. In contrast, metoclopramide (500 μg/kg, i.v.) increased PA, which was not accompanied by any change in PRA. Blood pressure was decreased by i.c.v. administration of dopamine and increased by i.c.v. injection of metoclopramide, whereas no change in blood pressure was observed when these compounds were administered i.v. Dopamine and metoclopramide, injected i.v. or i.c.v., did not produce significant changes in plasma sodium, potassium and corticosterone concentrations. These results suggest that the dopaminergic system in the brain regulates renin secretion, thereby changing PA. In contrast, dopamine receptors of the adrenal glands may inhibit aldosterone secretion, which is not mediated by changes in the renin-angiotensin system, plasma potassium and ACTH.

View full abstract

Blood pressure and sympathetic nerve activity were recorded before and after intracisternal injections of hypertonic NaCl solution in urethane anesthetized normotensive and deoxycorticosterone acetate (DOCA) hypertensive rats. Dose dependent pressor effects were recorded by intracisternal injections using normotensive Wistar rats. And the early phase of responses which were significantly depressed by blocking α-adrenergic receptors with phentolamine, accompanied by increased frequency of sympathetic nerve firing. Pressor responses and acceleration of the rate of sympathetic nerve firing produced by intracisternal injections of hypertonic NaCl were appreciably larger in DOCA hypertensives whose basal sympathetic nerve activity was elevated significantly than in normotensive rats. Pressor responses to intravenous injection of norepinephrine were also augmented, but responses to intra-cisternal injection were augmented more than those to norepinephrine injection. These findings suggest that sodium sensitive site which connects to pressor systems supposedly located around lower brain stem could be hypersensitive and eventually contribute to peripheral sympathetic hyperactivity in DOCA hypertension.

View full abstract