The effects of volume-loading and removal on mean blood pressure were evaluated in patients with high blood pressure and on chronic hemodialysis. Simultaneous measurements of plasma renin activity, plasma angiotensin II and plasma norepinephrine were made. The patients were divided into two groups according to their levels of plasma renin activity. Group 1 (n=10)( had a basal plasma renin activity below 2.5 ng/ml/hr while the level in group 2 (n=5) exceeded 2.5 ng/ml/hr. The mean blood pressure of the two groups was 105±5 mmHg and 107±4 mmHg, respectively. On the day of hemodialysis, saline loading (0.5 ml/kg/min for 20 min) was followed by routine hemodialysis. The mean blood pressure rose to 113±6 mmHg in group 1. However, the patients in group 2 did not respond to volume loading and hemodialysis. The plasma renin activity, plasma angiotensin II and plasma norepinephrine were not changed by volume loading in both group 1 and 2. Volume removal by hemodialysis caused a reduction in mean blood pressure in group 2 without alteration of vasoactive hormones. In group 1, the mean blood pressure was not reduced by hemodialysis, accompanied by increases in plasma renin activity, plasma angiotensin II, and plasma norepinephrine. In the high renin group, elevated circulating angiotensin II maintained a high blood pressure and in the low renin group, the renin-angiotensin system influenced the prevention of fall in blood pressure after hemodialysis. These results suggest that the renin-angiotensin system plays an important role in the regulation of blood pressure in relation to volume status regardless of whether the plasma renin activity is high or low.

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To investigate a relation between circadian blood pressure and heart rate variation, intra-arterial blood pressure (BP) and heart rate (HR) were recorded during 24 hours in 53 untreated essential hypertensives (EH), 8 secondary hypertensives, 10 normotensives (NT), and 3 patients with Shy-Drager syndrome. Values of systolic BP(SBP) and HR were sampled at about 10 second intervals throughout the 24-hour to calculate the coefficient of correlation between SBP and HR (r_SBP-HR). A significant positive correlation was found between SBP and HR levels in each subject of EH was WHO stage I and II, along with NT (average r_SBP-HR=0.59, 0.40, and 0.54 respectively, p<0.001). Low coefficients of correlation were found in the EH with WHO stage III (r=0.16) and the patients with pheochromocytoma (r=0.05). In contrast, a significant negative correlation was found in the patients with Shy-Drager syndrome (r=-0.44, p<0.001). Since HR is controlled mainly by the autonomic nervous system (ANS), the results suggest that the circadian variation of SBP is also mainly controlled by the ANS in the subjects with high r_SBP-HR and that of SBP controlled by the other factors in subjects with low r_&llt;SBP-HR>.

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To clarify the role of thromboxane A₂ (TXA₂) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B₂ (TXB₂: a stable catabolite of TXA₂) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 ( 8 mg/kg, i.v), a TXA₂ synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB₂ levels (424±138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB₂ levels (223±38 pg/m), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB₂ levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB₂ levels. In 3 patients, an EM rechanllenge at symptomatically quiescent stage resulted in negative test with augmented TXB₂ levels being markedly decreased. These findings indicate that increased TXA₂ in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA₂ production in the enhancement of coronary vascular spasticity.

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We attempted to differentiate between myocardial ischemia and left ventricular asynergy as the underlying mechanisms of exercise-induced ST-segment elevation in patients with previous myocardial infarction (MI). sixty patients with previous anterior MI, who underwent stress myocardial scintigraphy (SMS) and coronary angiography (CAG), which revealed a single vessel disease of the left anterior descending artery, were entered in this study. SMS and CAG were performed within 3 months of MI onset, and SMS and ECG were quantitatively analyzed. T wave changes to a complete upright position with concomitant ST-segment elevation (T-dominant ST-elevation) was seen in 56% of the patients with post-MI angina pectoris (N=16) and in 50% of those with significant redistribution in SMS (n=20). On the other hand, ST-segment elevation without T wave reversion (ST-dominant ST-elevation) was seen in 43% of patients with severe LV asynergy (akinesis and dyskinesis, n=39) and in 50% of those with severe scintigraphic defect in delayed images (relative thallium uptake &les;40%, n=10). When these findings were combined, T-dominant ST-elevation had sensitivity and specificity of 54% and 78%, respectively, for the diagnosis of myocardial ischemia, while the corresponding values for ST-dominant ST-elevation were 44% and 100%, for the diagnosis of severe ventricular asynergy. We conclude that the two underlying mechanisms, ischemia and asynergy, may produce different changes in ST-T shape in patients with previous myocardial infarction.

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To evaluate myocardial contractility in hypertrophic cardiomyopathy (HC), we obtained the end-systolic pressure-volume relation (ESPVR) and the end-systolic stress-volume relation (ESSVR) by changing loading conditions with Angiotensin II. The left ventricular (LV) stress-shortening relation was also analyzed in order to assess myocardial contractility. LV end-systolic pressure, end-systolic volume, end-systolic stress, and ejection fraction were obtained at rest and during Angiotensin II infusion with simultaneous recordings of pressure and volume in 9 patients with hypertrophic cardiomyopathy and 9 normal subjects (N). The slopes of ESPVR, Emax, showed no significant difference (HC: 3.1±2.3 vs N: 2.6±1.4 mmHg/ml, ns). The slopes of ESSVR were statistically similar (HC: 5.2±2.1 vs N: 6.0±2.8 g/cm² ml, ns). The slopes of end-systolic stress-ejection fraction relation were also in the same range in both groups (HC: -0.09±0.05 vs N: -0.10±0.05, ns). From these two different analyses of LV contractility, we conclude that myocardial contractility is normal in hypertrophic cardiomyopathy and not supernormal, at both chamber and muscle levels. Considering the increased muscle mass in hypertrophic cardiomyopathy (HC: 13446 vs N: 7419 g/m², p<0.01), the presence of increased numbers of contractile unites does not result in enhanced overall chamber contractility.

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Isopotential body surface maps during atrial excitation were examined by ten beats addition method of the P waves in 32 healthy children divided into three age groups. The moving pattern of the maxima and the minima, and the distribution of areas of positive and negative potentials in each group were similar to those of adults. Quantitative analysis of the duration and amplitude of the anterior and the left maximum, and the shift time from the former to the latter were done. In children the duration and amplitude of the anterior maximum were always larger than those of the left maximum in contrast to findings in adults where no significant difference was found in their values. The higher amplitude of the anterior maximum was found mainly in the youngest group. These parameters of the P maps were also examined in 12 cases of atrial septal defect (ASD). The amplitude and duration of anterior maximum were larger than those of healthy children at each age group, although the P wave by the conventional ECG did not reveal signs of right atrial overload. These results suggests that the body surface maps of the P waves are useful diagnostic methods to detect atrial disorders in children.

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Hypertrophy of the papillary muscle and apex cordis of the left ventricle was studied histopathologically using 84 hearts obtained at autopsy. The hearts were divided into three groups; a hypertrophy group (hear weight more than 350g); a borderline group (heart weight between 350 and 300g) and a control group (heart weight less than 300g). The size of the papillary muscle increased with increase in heart weight. Derangement of myocyte linings and fibrosis at the papillary muscle base became apparent with hypertrophy. In addition derangement and fibrosis extended from the internal to middle layers of the free wall with progressing hypertrophy. Derangement seemed to precede hypertrophy and fibrosis. A cluster of huge myocyte-like Purkinje's cells were associated with the center of the derangement. At the apex, criss-cross derangement developed from right and left side derangement with increasing hypertrophy. It is speculated that the focal derangement plays an important role in producing hypertrophy in response to mechanical stress with subsequent development of hypertrophy and fibrosis with some asymmetry.

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The change in coronary hemodynamics during right or left cardiac sympathetic nerve stimulation was studied in anesthetized open chest dogs. No difference in the increasing rate of mean coronary blood flow between right coronary artery (RCA) and left anterior descending coronary artery (LAD) was observed. However the increasing rate of right ventricular systolic pressure × heart rate (RVSP × HR) was greater than that of left ventricle (LV). With phentolamine injection, cardiac sympathetic nerve stimulation showed similar changes as the controls. Beta-stimulation by isoproterenol infusion did not cause different effects on the increasing rate of coronary blood flow between RCA and LAD. these results showed that cardiac sympathetic nerve stimulation increased the double product of the right ventricle (RV) more than that of the LV and the increase was not affected by phentolamine. Moreover, cardiac sympathetic nerve stimulation, either the right or the left, caused the greater effects on the RV compared to the LV mainly through beta-adrenoceptors, and that the response of the RV to increase in oxygen demand was possibly, in part, different from that of the LV.

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Ventriculo-arterial coupling states wee estimated by calculating left ventricular hydromotive pressure (Ps), source impedance (Zs) and input impedance (ZI) in 24 ;mongrel dogs with Fourier transforms of ventricular pressure and aortic flow immediately before and after instantaneous changes of arterial load. Calculated Ps (Psc) were compared with measured left ventricular iso-volumic pressures (Psm) in various inotropic and loading states. Psc wave-forms coinciding closely with those of Psm were obtained by cutting off higher frequencies within the fifth to tenth harmonics prior to the inverse Fourier transformation. The regression equation was Psc=1.08 Psm +0.68 (r=0.978). In control conditions, the ratio of Zs (0)/ Z1 (0) (function of frequency, 0=zero Hz) was close to the ratio of ejection phase to one whole cardiac cycle, and the ratio of peak Psm to left ventricular ejection pressure was 1.85±0.25 SD. These results imply the presence of a ventriculo-arterial load matching state in control conditions.

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The pituitary-adrenocortical response to ovine corticotropin-releasing factor (CRF) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) anesthetized with pentobarbital. After intravenous administration of various doses of CRF (0.1, 1.0 and 10μg), the plasma levels of ACTH were significantly increased in both groups. ACTH increments after various does of CRF were dose-dependent in WKY. ACTH increments after injections of 0.1, 1.0 and 10μg of CRF in SHR were 123.2±36.5 (SE), 123.0±52.2 and 60.3±48.5 pg/ml at 5 min, and 386.3±73.8, 243.4±86.6 and 220.0±31.4 pg/ml at 15 min, respectively. The ACTH increments in SHR at 15 min after administration of 0.1 μg of CRF were higher (p<0.02) than those in WKY. However, ACTH increments in SHR after administration of 10 μg of CRF were lower than those in WKY at 5 min (p<0.05) and 15 min. These data suggest that the plasma ACTH responses to various does of CRF represent a dose-unrelated plateau response in SHR. The plasma levels of corticosterone after administration of various does of CRF did not change significantly and there were no significant differences between the two strains. The results of these experiments suggest that SHR have an abnormal reponse of the pituitary-adrenocortical axis to CRF, and the abnormal response may be attributable to desensitization of the pituitary to CRF.

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A comparison of blood flow and myocardial O₂ consumption (MV^^.O₂) in the right and the left ventricles was made in dogs whose chests had been opened. The effect of volume loading by arterio-venous and arterio-left atrial shunts, and the effect of ventricular hypoperfusion by rapid removal of blood were examined in the presence and absence of the pericardium. Blood flow per unit myocardium was greater in the left anterior descending coronary artery (LAD) than in the right coronary artery (RCA), 75±4.3 vs. 46±2.8 (mean±SE)ml/min per 100g, respectively. Similarly, the myocardial O₂ extraction ratio (EO₂) was 59±2% in the left ventricle and 43±3% in the right ventricle (p<0.001). The MV^^.O₂ was greater for the left than for the right ventricle, 8.0±0.6 vs. 3.5±0.3 ml O₂/min per 100g. volume loadiing to both ventricles by arterio-venous (AV) shunt increased MV^^.O₂ of the right ventricle by augmented EO₂ in addition to a rise in the coronary arterial blood flow. Decrease in aortic pressure by rapid removal of blood increased EO₂ in both ventricles. The increments of EO₂ were greater in the right ventricle than in the left ventricle, 54 vs. 31% (p<0.01). When the pericardium was closed with suture, right and left end-diastolic pressure rose, but EO₂ and coronary blood flow of both ventricles did not change. We conclude that reserve capacity of myocardial O₂ extraction was greater in the right ventricle than in the ventricle.

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The gross anatomic and microscopic appearance of the hearts of young and adult WKY/NCrj rats was examined in comparison with that of normotensive Wistar and SHR/NCrj rats. In a substantial number of the WKY rats, the heart weight and thickness of ventricular septum were much greater than those of the Wistar and SHR rats. The ventricular septum to left ventricular free wall thickness ratio was greater than 1.3 in about one sixth of the WKY rats. In most of the hypertrophied WKY hearts, the transverse area of the left ventricular cavity was smaller in relation to the wall area than in the Wistar and SHR rat hearts, although in a few it was greater. Abnormal fiber arrangement, myocyte hypertrophy, and myocardial fibrosis were far more prominent in the hypertrophied myocardium of the WKY rats compared with the Wistar of SHR rats. Intramural arteries with marked wall thickening existed frequently in the hypertrophied and dilated hearts. Electron microscopic examination revealed marked disarrangement of bundles of myofilaments and widened Z-bands in the hypertrophied myocardium. blood pressure was not elevated in the rats with cardiac hypertrophy. These findings show that a disease of the myocardium with the pathologic features similar to those of hypertrophic cardiomyopathy in man occurs spontaneously in rats.

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The purpose of the present study is twofold, firstly to investigate the effects of alpha-human atrial natriuretic polypeptide (α-hANP) on norepinephrine overflow from sympathetic nerve endings, and secondly to compare vascular responsiveness in perfused mesenteric preparations in spontaneously hypertensive rats (SHR, Okamoto and Aoki, 7-9 weeks old) and a cohort of Wistar Kyoto rats (WKY). In preliminary studies using normotensive Wistar rats, the pressor responses to electrical nerve stimulation or exogenous norepinephrine application were inhibited by α-hANP. Norepinephrine overflow was also suppressed by α-hANP, during nerve stimulation. The pressor responses and norepinephrine overflow during nerve stimulation were significantly greater in SHR than in WKY rats. The inhibitory effect of α-hANP on these responses was reduced in SHR. These results indicate that α-hANP could affect both pre- and post-synaptic sites of the resistance vessels. Further, the reduced inhibition of pressor responses and norepinephrine overflow by -hANP in SHR suggests an insufficient regulation of adrenergic transmission by -hANP in hypertension.

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