Search

中高年肥満女性を閉経前群, 閉経後群に分け, LDL-コレステロール (LDL-C) および内臓脂肪に影響を及ぼす食事因子を, 3カ月間の減量指導による内臓脂肪減少時および減量指導終了より1年後の内臓脂肪増加時について検討した。減量指導開始時に, BMIは群間に有意差を認めないにも関わらず, 内臓脂肪, LDL-Cは閉経後群が閉経前群に比し有意に高値を示した。減量指導後, 体重, BMI, 内臓脂肪は両群ともに有意に低値を示し, LDL-Cは閉経前群でのみ有意に低下し, 閉経後群は低下傾向を示したが有意ではなかった。LDL-Cの減少に内臓脂肪が正の相関を示し, 閉経後群で有意であった。重回帰分析の結果より, 閉経後群のLDL-Cの減少に内臓脂肪と砂糖摂取量, 脂質エネルギー比が正の関連を認め, 内臓脂肪の減少には嗜好飲料類摂取量が閉経の有無に関係なく有意な正の関連を認めた。減量指導終了より1年後, 標準体重当りエネルギー摂取量は両群ともに有意に増加し, 内臓脂肪は増加傾向を示し, LDL-Cは両群ともに有意に上昇した。内臓脂肪の増加に砂糖摂取量が正の相関を閉経後群で示し, エネルギー補正後も有意であった。以上より, 中高年肥満女性のLDL-Cの減少に内臓脂肪が正に関与し, 内臓脂肪の変動にはショ糖および脂質が閉経の有無に関係なく正に関与することが示唆された。

Insulin resistance is thought to raise blood pressure. Recently, a significant positive relationship between mean blood pressure and plasma leptin levels, but there have been no reports dealing with the relationship between blood pressure and either insulin resistance or serum leptin levels after weight loss. In the present work, we attempted to clarify the relationship between changes in blood pressure and either the serum leptin level or the insulin level in 102 moderately obese females (mean body mass index (BMI), 29.5 +/- 0.5 kg/m2; age, 47.0 +/- 0.9) during a 3 month period. No differences in age, fat-mass, homeostasis model assessment (HOMA), the summation of insulin (sigmaIRI), plasma renin activity (PRA) or 24 h norepinephrine excretion (24hU-NE) were observed between the hypertensive (HT) group (n = 31) and normotensive (NT) group (n = 71) before weight loss, but the basal serum leptin was significantly higher in the HT (16.8 +/- 1.1 ng/ml) than in the NT group (15.2 +/- 0.8 ng/ml), after adjusting for abdominal total fat. After a 3 month weight reduction program, the total abdominal fat, serum leptin and sigmaIRI significantly decreased in both groups. The systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 144/84 to 130/77 mmHg only in the HT but not in the NT group. The PRA decreased in both groups, while the 24hU-NE significantly decreased only in the HT group. The changes in the leptin level were significantly correlated with the changes in both sigmaIRI and HOMA after weight loss in the two groups, respectively. Finally, a statistically significant positive correlation was observed between the changes in the leptin and the changes in the mean blood pressure (MBP) (r = 0.412, p < 0.05) only in the HT group. Multiple regression analysis revealed that the changes in MBP were independently associated with the changes in 24hU-NE and the changes in either sigmaIRI or HOMA in all subjects. However, a statistically significant positive correlation was observed between the changes in MBP and the changes in leptin levels even after adjusting for the total abdominal fat, 24hU-NE and either sigmaIRI or HOMA (both expressed as a percentage of the baseline value) in a multiple regression analysis only in the HT group. These results suggest that leptin may play a role in the pathophysiology of obese hypertension.

We developed an animal model of coronary spasm in swine, similar to coronary spasm in patients with variant angina based on the angiographic findings. In this animal model, an impairment of endothelium dependent dilatation appeared to play a minor role while the hypercontraction of the medial muscle cells by histamine and serotonin at the spastic site played a major role in the induction of coronary spasm. In Gottingen male miniature swine receiving focal endothelial denudation, moderate hypercholesterolemia and X ray irradiation, the abrupt, severe and prolonged coronary spasm resulted in a sudden progression of organic coronary stenosis mainly due to intraplaque hemorrhage and also in acute myocardial infarction.

In a double-blind, placebo-controlled study, thirty-three subjects were allocated to undergo either a 4-week treatment with oral Mg supplementation (Mg(OH)2; 411–548 mg Mg/d) or a placebo. The urinary excretion of Mg increased significantly in both the first 2 weeks and the following 2 weeks of Mg supplementation, while the urinary Na excretion also increased significantly over the experimental period. The systolic and diastolic blood pressure values decreased significantly in the Mg group, but not in the placebo group. The urinary aldosterone excretion and packed cell volume increased significantly during the last 2 weeks of the experimental period compared with the run-in period and first 2 weeks of supplementation. There was a statistically significant positive correlation between the values for urinary noradrenaline excretion and diastolic blood pressure at the end of the supplementation period (both expressed as a percentage of the run-in value). Statistically significant increases in lecithin-cholesterol acyltransferase (EC2.3.1.43; LCAT), HDL-cholesterol and apolipoprotein AI were also observed after Mg supplementation. A significant positive correlation was observed between the levels of LCAT and urinary Mg excretion for the experimental period (expressed as a percentage of the run-in value). The total cholesterol: HDL-cholesterol ratio decreased significantly during the last 2 weeks of Mg supplementation compared with the first 2 weeks and the run-in periods, but this did not occur in the placebo group. These results suggest that Mg supplementation may lower blood pressure through the suppression of the adrenergic activity and possible natriuresis, while also improving the serum lipids through the activation of LCAT in human subjects.

1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced in a concentration-dependent manner both the [Ca2+]i and tension, irrespective of whether the strips were unstimulated or exposed to either high K+ or histamine containing solutions. However, both in the case of contractions induced by high K+-depolarization and histamine stimulation, for a given [Ca2+]i elevation the tension which developed in the presence of nipradilol was smaller than that generated in its absence, so that the [Ca2+]i-tension curves during the contraction were shifted to the right. 3. In the absence of extracellular Ca2+, the [Ca2+]i elevation due to the release of Ca2+ from histamine-sensitive store was inhibited by nipradilol. Nipradilol had no effect on the [Ca2+]i elevation due to the release of Ca2+ from caffeine-sensitive stores; however, it did inhibit the caffeine-induced increase in tension. A derivative of nipradilol, which lacked a nitroxy molecule (Nip(-N)), had no effect on the [Ca2+]i and tension elevated by histamine or caffeine in the absence of extracellular Ca2+. 4. The beta-adrenoceptor agonist, isoprenaline, reduced [Ca2+]i tension when applied to steady state contractions induced by high K+, or at the peak level of tension to histamine. The reduction of [Ca2+]i and tension induced by isoprenaline was inhibited by Nip(-N) in a concentration-dependent manner and nipradilol inhibited the isoprenaline-induced relaxation with bell-shaped concentration-response curves. At lower concentrations, nipradilol acted as a beta-blocker, the IC50- value being smaller than that of Nip(-N), and at higher concentrations, it acted as a nitrovasodilator. 5. Thus, it is suggested that, at lower concentrations, nipradilol, an antianginal drug, acts as a beta-adrenoceptor antagonist. At higher concentrations, it relaxes the proximal portion of the coronary artery by directly reducing [Ca2+]i and the Ca2+-sensitivity of the myofilaments, apparently due to the presence of the nitroxy molecule.

The effects of a new calcium antagonist, CD-832, on coronary and systemic hemodynamics were compared with those of nifedipine in conscious dogs. A pair of 10-MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery (LCX) under sterile conditions to measure epicardial coronary artery diameter (CoD) and coronary blood flow (CBF), respectively. CD-832 (30, 100, and 300 micrograms/kg) and nifedipine (3, 10, and 30 micrograms/kg) produced dose-related increases in large epicardial CoD and in CBF. At doses of CD-832 (100 micrograms/kg) and nifedipine (30 micrograms/kg), producing the same increases in CoD and CBF, the duration of increases in CoD and in CBF was markedly longer after CD-832 than after nifedipine. CD-832 and nifedipine produced dose-related decreases in aortic blood pressure (AoP) and reflex increases in heart rate (HR). However, nifedipine produced significantly (p < 0.01) greater tachycardia than CD-832 in equieffective hypotensive doses. These results demonstrate that CD-832 produces sustained dilation of both large epicardial coronary arteries and small resistance vessels and that the degree of tachycardia after CD-832 is significantly less than that after nifedipine.

The objective of this study was to examine the prevalence and pathogenesis of silent myocardial ischemia during exercise following myocardial infarction. Exercise-induced myocardial ischemia was assessed by 201Tl-SPECT (single photon emission computed tomography) 4.5 weeks after acute myocardial infarction in 229 patients. Exercise-induced myocardial ischemia occurred in 109 patients (48%), and 72 (32%) had silent ischemia. Although the prevalence of multivessel coronary artery disease was similar between patients with silent and symptomatic ischemia, the size of reversible myocardial ischemia was larger in patients with symptomatic ischemia than in those with silent ischemia (21.3 +/- 3.0% vs 13.2 +/- 1.9% of LV, p0.05). The incidence of reversible ischemia remote from the infarct area was higher in patients with symptomatic ischemia than in those with silent ischemia (30% vs 17%, p0.10). The cause of silent ischemia after myocardial infarction may be closely related to the smaller size of reversible myocardial ischemia. Ischemia remote from, or adjacent to, the infarct area could be a factor in determining the presence or absence of pain.

BACKGROUND Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

The role of changes in preload in maintaining stable hemodynamics during coronary obstruction was assessed in the presence of myocardial ischemia due to occlusions of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. Changes in preload (mean left atrial pressure) to maintain a constant stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed sonomicrometrically. Ventricular function curves relating left atrial pressure to stroke volume were assessed during a control state and after I min of coronary occlusion. The extent of preload reserve after coronary occlusion was examined on the ventricular function curves and was defined as the change in mean left atrial pressure required to maintain stroke volume at the level of the control state under conditions of regional ischemia. Ischemic size was determined by a stereo-angiogram after the animals were sacrificed. The extent of preload reserve (X) was linearly related to the ischemic size (Y) in both LAD (Y=0.90+0.16X, r=0.76, p

Left ventricular hypertrophy has been reported after ascending aorta-abdominal aorta bypass, despite seemingly insignificant changes in cardiac output and mean arterial pressure. Such a bypass procedure may be used for the treatment of complex coarctation of the aorta, hypoplastic aortic arch, or thoracoabdominal aortic aneurysm. To investigate the effect of the bypass procedure on left ventricular afterload, we measured aortic input impedance in six open chest dogs by placing a knitted Dacron graft from the ascending aorta to the abdominal aorta and occluding the aortic arch. Cardiac output and mean arterial pressure remained unaltered throughout the experiment, consistent with clinical reports. Systolic pressure increased by 25% of control, and the ratio of diastolic pressure-time index to tension-time index decreased by 27%. The measured input impedance was then approximated with the three-element windkessel model, which consists of resistance, compliance, and characteristic impedance (average of impedance modulus between 5 and 15 Hz). There was no change in resistance and compliance; characteristic impedance increased to 255% of control. Connecting an air chamber to the vascular prosthesis doubled the compliance and decreased the characteristic impedance nearly to the control value without altering resistance. It also reduced the systolic pressure by 14% of the bypass protocol and increased the ratio of diastolic pressure-time index to tension-time index (by 32% of control value and 82% of bypass value). Arterial systolic pressure and pulse pressure were both linearly correlated with the characteristic impedance. Thus we conclude that although ascending aorta–abdominal aorta bypass does not affect cardiac output, mean arterial pressure, resistance, or compliance, it does increase characteristic impedance. Left ventricular systolic load is directly correlated with characteristic impedance. Increased systolic wall stress might be the cause of left ventricular hypertrophy of the previously reported cases. Because decrease in the distensibility of the proximal aorta is one of the factors causing the increase in characteristic impedance, using a compliant graft might help to unload the heart.

1. We examined temporal changes in the relationship between cytosolic calcium concentrations ([Ca2+]i) and developed tension during histamine-induced contractions of strips of the coronary artery of the pig, by making use of simultaneous measurements of fura-2 fluorescence and force. 2. The relationship between [Ca2+]i and developed tension observed with cumulative applications of extracellular Ca2+ ([Ca2+]o), ranging from 0 mM to 10 mM, during 118 mM K(+)-depolarization was similar to that observed in chemically skinned strips of the porcine coronary artery, as noted by other investigators. [Ca2+]i at 0 mM [Ca2+]o, at 50% of maximum, and at maximum tension development were 76 nM, 424 nM, and 3050 nM, respectively. 3. Cumulative applications of histamine induced dose-dependent increases in [Ca2+]i and tension and the extent of tension for a given change in [Ca2+]i increased, i.e. greater effectiveness of [Ca2+]i-tension relationship, than seen with K(+)-depolarization. 4. When histamine 10(-5) M was applied, [Ca2+]i abruptly rose and reached the first peak within several seconds. After a slight dip at 30 s, [Ca2+]i reached a second peak at 3 min, and then gradually declined. On the other hand, tension developed rapidly reached a maximum at 4 min, then gradually declined. The relation between [Ca2+]i and tension in the early, rising phase of contraction was similar to that obtained during depolarization. At the time of maximum tension development, the relation was greater than that observed during depolarization, which persisted in the phase of declining tension. 5. To examine the role of protein kinase C in the increased effectiveness of [Ca2+]i-tension relation of histamine-induced contractions, we used 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7), as an inhibitor. Exposure of strips to H-7, i0-' M, reduced the effectiveness of [Ca2+]i-tension relation toward the level observed during depolarization, while it had no effect on the [Ca2 ]i-tension relation in the early phase of contraction either in the presence or absence of extracellular Ca2 + 6. In intact smooth muscle of the coronary artery of the pig, the relationship between [Ca2+]i and developed tension varies during contraction. Histamine, a receptor-mediated stimulus, induced a greater tension for a given change in [Ca2+]i during the steady state of contraction than did depolarization. The greater effectiveness of contraction, particularly in the later phase, seems to be mediated by activation of an H-7-sensitive mechanisms.

1. By use of front-surface fluorometry and fura-2-loaded strips of the coronary artery of the pig, the effects of nitroglycerin (NG) on cytosolic Ca2+ concentrations ([Ca2+]i) and on tension development were measured simultaneously. 2. Both high K+ depolarization and histamine increased [Ca2+]i and tension in a concentration-dependent manner. However, the tension development in relation to the [Ca2+]i increase ([Ca2+]i-tension relation) observed with histamine was much greater than that observed with K+ depolarization. 3. NG reduced in a concentration-dependent manner both [Ca2+]i and tension, irrespective of whether the vascular strips were in a resting state or during exposure to high K+ or to histamine stimulation. However, the extent of reduction in tension (relaxation) was greater than that expected from the reduction in [Ca2+]i based on the [Ca2+]i-tension relationship observed with K(+)-depolarization. 4. In the absence of extracellular Ca2+, NG depleted stored Ca2+ and also inhibited Ca2+ release from histamine-sensitive stores, but had no effect on the caffeine-sensitive stores. NG inhibited the caffeine-induced tension development with no change in [Ca2+]i. 5. We suggest that NG relaxes the coronary artery of the pig by reducing [Ca2+]i and also by directly controlling contractile elements through second messengers not related to changes in [Ca2+]i.

Mechanisms of blockade of two types of Ca2+ channels by the organic Ca2+ antagonists, nicardipine, diltiazem, verapamil, and flunarizine, were examined in rat aorta smooth muscle cells in primary culture by using the whole-cell voltage-clamp method. T-type Ca2+ current (T-type ICa) was isolated by an internal perfusion of 5 mM F-, which irreversibly suppressed the L-type ICa, without affecting T-type ICa. L-type ICa was isolated by setting a holding potential at -60 mV, at which most of the T-type Ca2+ channels were inactivated. L-type ICa is halved by 0.1 microM nicardipine, 3.0 microM diltiazem, 0.6 microM verapamil, and 0.1 microM flunarizine, whereas T-type ICa is halved by the same drugs at 0.6, 30, 30, and 0.1 microM, respectively. Diltiazem and verapamil accelerated the decay of L-type ICa and cumulatively blocked L-type ICa during repetitive step depolarizations elicited every 30 seconds ("use-dependent block"). Diltiazem and verapamil neither changed the decay of T-type ICa nor showed a use-dependent block of T-type ICa. Nicardipine and flunarizine blocked both L- and T-type ICa from the first depolarization step after drug treatment ("tonic block") and shifted their steady-state inactivation curves to the left. The estimated binding constants of nicardipine and flunarizine for the inactivated state of T-type Ca2+ channels (48 and 19 nM, respectively) were smaller than those for the resting state of L-type Ca2+ channels (160 and 90 nM, respectively). A low concentration (0.1 microM) of nicardipine initially potentiated T-type ICa and then reduced it. We conclude from these results that 1) nicardipine and flunarizine block not only the resting state but, more preferentially, the inactivated state of both the L- and T-type Ca2+ channels; 2) verapamil and diltiazem preferentially act on the open state of the L-type Ca2+ channel and on the resting and inactivated state of the T-type Ca2+ channel; and 3) the T-type Ca2+ channel of the rat aorta smooth muscle cells appears to be more sensitive to nicardipine and flunarizine than does the L-type Ca2+ channel at around the resting membrane potential.

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n = 7) and age-matched normal subjects (n = 7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of alpha-human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial alpha-human ANP in patients with heart failure was considerably less (p less than 0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p less than 0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects.

The maximal exercise capacity of patients with congestive heart failure (CHF) is frequently decreased because of decreased skeletal muscle oxygen utilization. In this study we examined whether forearm oxygen utilization is decreased during dynamic handgrip exercise in patients with CHF and whether captopril improves forearm oxygen utilization. They were divided into 3 groups according to the level of plasma renin activity (PRA) and New York Heart Association functional classification (NYHA): Group 1 consisted of 7 normal (control) subjects (PRA: 0.5 +/- 0.2 ng/ml/h, NYHA: 0); Group 2, 7 patients with severe CHF (PRA: 11.3 +/- 3.9 ng/ml/h, NYHA: 3.6 +/- 0.3); Group 3, 4 patients with mild CHF (PRA: 2.4 +/- 0.2 ng/ml/h, NYHA: 2 +/- 0). Forearm blood flow was measured by a strain gauge plethysmograph at rest and during dynamic handgrip exercise. Regional arterial venous oxygen content was measured and forearm oxygen consumption was calculated by the Fick principle. Forearm blood flow was less (p less than 0.05) at rest and during exercise in patients with severe CHF than in control subjects; this was compensated for by increased oxygen extraction, thus maintaining forearm oxygen consumption at a normal level at rest and during submaximal exercise. During maximal exercise, oxygen extraction was not different between normal control subjects and patients with severe CHF, thus forearm oxygen consumption was significantly less (p less than 0.01) in patients with severe CHF than in control subjects. In patients with mild CHF, forearm blood flow, oxygen extraction and oxygen consumption were not different from those in normal control subjects. Captopril (25 mg orally) did not alter forearm hemodynamics at rest and during exercise in control subjects and patients with mild CHF. In patients with severe CHF, captopril lowered systolic and mean blood pressure (p less than 0.05). Captopril increased forearm oxygen extraction (p less than 0.05) and tended to increase blood flow and thus increased oxygen consumption (p less than 0.01) during maximal exercise. Our data indicate that oxygen utilization was impaired in patients with severe CHF and that captopril improved forearm oxygen utilization during maximal handgrip exercise in patients with severe CHF.

In the cooperative, multi-center trial, 491 medically treated patients with coronary artery disease were thoroughly assessed and followed for an average of 49 months. The rate of cardiac death and/or non-fatal myocardial infarction was 9.8%; 64% of cardiac events were fatal. Three factors, such as number of diseased coronary arteries, other diseased organs and the cardiothoracic ratio, contributed significantly to the evolution of cardiac events. The outcome of cardiac events in Japan in the period from 1973 to 1985 in patients with coronary artery disease was more favorable than those reported recently in the United States. The results of this study will serve as a control data base for further studies in Japan.

The purpose of this study was to investigated the effect of weight loss on blood pressure and its related variables in moderately obese Japanese females, including an investigation of the rebound phenomenon. Study I examined the effects of weight loss on blood pressure in 138 moderately obese, nondiabetic females (BMI 29.3±0.3 kg/m2; age, 46.3±0.8 years) during a 3-month therapeutic dietary and exercise program. Study II investigated the effect of weight rebound on blood pressure over an additional 21 months of exercise in 48 subjects from Study I subjects. After 3 months, the BMI significantly decreased to 27.9±0.3 kg/m2. Abdominal total fat, visceral fat (V), and subcutaneous fat (S) also decreased significantly. In addition, the summation of insulin (ΣIRI), plasma glucose (ΣPG) and HOMA during 75 g oral glucose tolerance test also all significantly decreased. Significant decreases in both the SBP and DBP were observed after the 3 month weight reduction program. Multiple regression analysis revealed that the reduction in SBP was significantly and positively associated with the reduction in log ΣIRI and the reduction in log 24h-urinary norepinephrine excretion at the end of Study I. The DBP showed a significantly positive association with the log ΣIRI. With regard to the weight rebound phenomenon, Study II showed that the SBP, DBP and ΣIRI all increased significantly, and a positive correlation was observed between the changes in the SBP and those in the log ΣIRI. However, no such correlation was observed regarding the abdominal total fat and visceral fat during both periods. These results suggest that weight loss therefore caused the BP to decrease due to both an improvement in hyperinsulinemia and a decrease in the adrenergic activity which may be involved in the urinary catecholamine. As a result, hyperinsulinemia is thus considered to play an important role in the pathogenesis of blood pressure due to obesity not only during weight loss, but also during the weight rebound phenomenon. (Hypertens Res 2001; 24: 481-487)

To clarify whether acute medial necrosis of the aorta induces aneurysms and intimal thickening at a later stage, we first attempted to induce acute aortic medial necrosis in 47 normal rabbits by the administration of Russell's viper venom intraperitoneally and of angiotensin II intravenously as used in a previous study and then followed the rabbits for 1 and 2 months respectively. As a control, 18 adult normal rabbits were used. Six control and 20 treated rabbits were sacrificed after aortagraphy at the end of one month, while the remaining 12 control and 27 treated rabbits were sacrificed at the end of 2 months. We evaluated the aortic lesions by gross observations and both light and electron microscopic examinations. In addition, at the end of one month, aortagraphy was performed to measure the luminal diameter of the aorta of the 6 control and 20 treated rabbits. We macroscopically found the saccular lesions to be surrounded by small crater like lesions mainly at the thoracic aortas in 18 out of 47 treated rabbits. These lesions consisted of the necrosis and calcification of the aortic media and the destruction of the elastic fiber along with intimal thickening. However, no aneurysmal dilatation was found in the aortagraphy findings. We thus conclude that acute medial necrosis produced saccular and crater like lesions but these lesions were not confirmed by aortagraphy.

The aim of this study was to evaluate the relationship between changes in abdominal fat areas and the baseline serum leptin levels of Japanese obese women during weight reduction. The study was performed on 100 obese female Japanese volunteers. We measured the BMI and abdominal fat areas (visceral, subcutaneous and total) by magnetic resonance imaging and determined the fasting serum leptin levels before and after a 3 month weight reduction program. We examined whether or not a relationship exists between the baseline leptin levels and the subsequent changes in the abdominal fat areas after a weight reduction program. Multiple linear regression analysis was performed to examine the relationship between the baseline leptin levels and changes in abdominal visceral, subcutaneous, and total fat areas, and demonstrated that the baseline leptin level was a significant predictive factor for changes in the abdominal visceral fat area in both pre and postmenopausal Japanese obese women. We thus concluded the relatively higher baseline leptin levels in Japanese obese women to be associated with a relatively smaller reduction in the amount of abdominal visceral fat after undergoing a weight reduction program.

Two thousand, seven hundred and thirty-three patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography and discharged alive, were followed for an average of 2.9 years. During the follow-up period, 212 patients (7.6%) died. The factors that governed the prognosis of myocardial infarction after discharge were advanced age, female gender, obesity, previous infarction, angina pectoris more than 1 month before the onset of AMI, post-infarction angina, multiple-vessel diseases, advanced stage by Killip's and/or Forrester's classification on admission, elevated pulmonary capillary arterial pressure, decreased cardiac index, decreased left ventricular ejection fraction, increased left ventricular end-diastolic volume and left ventricular aneurysm before hospital discharge. Patients with ventricular tachycardia or ventricular fibrillation during hospitalization showed a poor prognosis. In contrast, patients who received intracoronary thrombolysis, or emergent and/or elective percutaneous transluminal coronary angioplasty showed a favorable prognosis.

The subjects consisted of 2,733 patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography, and discharged alive. The patients were followed for an average of 2.9 years after discharge. During the follow-up period, re-infarction occurred in 172 patients (6.3%). The factors associated with re-infarction were total cholesterol of more than 250 mg/dl, HDL-cholesterol of less than 35 mg/dl and diabetes mellitus. The rate of re-infarction was also high in patients who had had a previous infarction before admission, angina pectoris before or after the onset of AMI or multiple-vessel disease. In contrast, intracoronary thrombolysis reduced the rate of re-infarction.

This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4 +/- 2.3% and 3.8 +/- 0.8% (p less than 0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1 +/- 1.1% to 2.7 +/- 1.0% (p less than 0.01) at the denuded site and from 4.2 +/- 0.6% to 0.8 +/- 0.3% (p less than 0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimal thickening and regenerated endothelium in the denuded site.(ABSTRACT TRUNCATED AT 250 WORDS)

A segmental wall motion abnormality is an unusual finding in patients with hypertrophic cardiomyopathy. To clarify its clinical significance, 48 patients with hypertrophic cardiomyopathy were analyzed. Eight patients (Group A) had apical segmental dysfunction; 40 (Group B) had normal wall motion. No patient in either group had coronary artery stenosis on selective coronary arteriography. In all patients in Group A, apical segmental dysfunction was revealed by left ventriculography; however, it could be detected by echocardiography in only two patients in Group A. Left ventricular hypertrophy by electrocardiogram (ECG) was more common in Group B (p less than 0.05). Abnormal Q waves were more frequently discovered in Group A (p less than 0.005) and were recognized predominantly in the lateral leads. On serial ECGs, a gradual development of abnormal Q waves was noted in six of eight patients in Group A. Malignant arrhythmias were more common in Group A (p less than 0.001). In two patients in Group A, left ventricular dilation and congestive heart failure developed during the follow-up period. Thus, the presence of a Q wave in the lateral leads on an ECG in patients with hypertrophic cardiomyopathy may indicate the presence of apical segmental dysfunction. Left ventriculography should be performed to examine the presence of this abnormality and 24 h ambulatory ECG monitoring should be done to detect malignant arrhythmias in patients who have abnormal Q waves in the lateral leads. Patients with this unique type of hypertrophic cardiomyopathy need careful follow-up evaluation.

In order to clarify the incidence of unstable angina (UA), the rate of mutual transition to other forms of ischemic heart disease, and the short term prognosis of asymptomatic patients, we followed prospectively 421 medically treated patients after through assessment of coronary artery disease for an average of 43 months. Three hundred and two episodes of UA had occurred in 139 patients. Of these 14 patients experienced major cardiac events. Sixteen patients had sudden cardiac events with no prior UA. Two hundred and sixty-six patients had no episodes of UA nor cardiac events; of these, 97 patients were followed for more than 49 months. Those with both effort and rest UA had a much more higher incidence of unstable episodes and a higher average age than those with effort UA alone and those with rest UA alone. The average transition rate to the cardiac events by month of patients with UA, by markovian analysis, was higher than those of the asymptomatic or stable angina patient groups. When background factors are taken account, these transition rates might help the physicians in determining the treatment of patients with ischemic heart disease at a specific stage of state.

Two siblings presented with symptoms of left ventricular dysfunction and ventricular arrhythmias. Echocardiography and left ventriculography revealed dilatation, diffuse hypokinesis and apical aneurysm of the left ventricle in both cases. Myocardial infarction was unlikely by history and examinations. We diagnosed them as cases of familial dilated cardiomyopathy complicated by left ventricular aneurysm.

Effects of retrograde coronary venous perfusion on oxygen supply and energy metabolism of ischemic myocardium of the isolated perfused rat heart were examined by means of NADH fluorescence photography. Occlusion of the left coronary artery produced regional ischemia of the left ventricular free wall, as evidenced by the sharply demarcated increase in NADH fluorescence. During ischemia, a narrow area of minimal fluorescence (140 +/- 10 microns), indicating sufficient oxygenation for oxidative phosphorylation, was observed around the epicardial coronary veins in the ischemic lesion. Retrograde perfusion was introduced through the coronary vein (left cardiac vein) that drained off the ischemic area, which resulted in a marked reduction of the area of increased NADH fluorescence in the epicardial surface. In the cross-sectional view, although the myocardium of the entire ischemic area induced by left coronary artery occlusion could be perfused by venous retroperfusion, the effect on reduction of the area of increased NADH fluorescence was seen only in the epicardial half of the myocardium. Retrograde coronary venous perfusion also resulted in a small increase in tension development (P less than 0.05), a decrease in resting tension (P less than 0.01), and partial preservation of myocardial high energy phosphate content (P less than 0.01). We propose that coronary venous retroperfusion improves oxygenation, partially preserves oxidative phosphorylation in the epicardium, and improves contractile function in the ischemic region.

Using two-dimensional (2-D) echocardiography we evaluated the applicability of the left ventricular (LV) short axis view combined with manual scanning technique for the detection and evaluation of aneurysms of the membranous ventricular septum (AMS). In 12 patients with angiographically proven AMS, we recorded from the left sternal border the short axis view of the left ventricle continuously displayed from the aortic to the ventricular level by tilting the transducer manually along the LV long axis plane. We then compared the detectability of AMS by this method with that by other standard fixed 2-D echocardiographic views. This method proved to be best for the detection of AMS (12/12), followed by an apical four-chamber view (10/12), a parasternal LV long axis view (8/12) and an apical two-chamber (2/12) view. For the detection of AMS and for three-dimensional evaluation of the structure of the AMS and the original orifice of ventricular septal defect the method was shown to be clinically applicable.

The renal parenchyma of 5 crub-eating monkeys (Macaca irus) was wrapped by cellophane, and plasma renin activity, blood pressure and vascular permeability of ocular ground were measured in comparison with 5 unoperated control monkeys. The results demonstrated that increases of systolic arterial pressure, plasma renin activity, and permeability of the retinal vessels were found in 4 operated monkeys. There was no such abnormal finding in the unoperated control monkeys. Generally there was a rough parallelism among levels of plasma renin activity and systolic blood pressure, an increase of permeability of retinal vessels and fibrinoid angionecrosis and/or necrotizing angitis similar to polyarteritis nodosa.

The effects of 8-bromoguanosine 3′:5′-cyclic monophosphate (8-Br cGMP) on intracellular free calcium concentrations ([Ca2+]i) in cultured rat aortic vascular smooth muscle cells (VSMCs) loaded with fura-2 were recorded microfluorometrically. Irrespective of whether VSMCs were at rest (in 5 mM K+ PSS), under Ca2+ depletion (in Ca2+-free medium for 10 min) and K+ depolarization (in high K+ PSS), [Ca2+]i was actively reduced and reached a new and lower steady-state level with the application of 8-Br cGMP. This may be the first and direct evidence that cGMP, a putative mediator of various vasodilators, actively reduces [Ca2+]i in VSMCs.

The effects of chronic instrumentation on regional myocardial performance and regional myocardial blood flow were studied in 8 mongrel dogs. Regional segment lengths were measured by an ultrasonic dimension gauge technique at two areas of the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). Regional myocardial blood flow was measured by a tracer microsphere technique. These measurements were repeated while the animals were conscious on the 4th, 11th, 21st and 28th days after instrumentation. On the 4th day, the heart rate was rather high and regional shortening at both the LAD and LCX areas remained suppressed. After the 11th day, hemodynamic variables such as heart rate, left ventricular pressure and regional wall motion were fairly constant. Regional myocardial blood flow and its distribution were also constant throughout the experimental period. Fibrosis of the epicardium invariably induced by surgical procedures did not affect the distribution of regional blood flow as compared with that of the interventricular septum. Thus, a stable hemodynamic state was recorded after the 11th day following surgical manipulation and the implantation of sensors and catheters did not affect the level of regional myocardial blood flow or its distribution at rest. Such long term reproducible measurements of regional wall motion and regional myocardial blood flow may facilitate chronic studies of cardiovascular physiology.