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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.

The aim of our study was to investigate the association between nutrient factors and the osteo-sono assessment index (OSI) for calcaneus of young Japanese women. The subjects consisted of 965 young women aged from 18 to 22 years studying at the Department of Food and Nutrition at Nakamura-Gakuen University. The OSI was measured by ultrasonic bone absorptiometry. We found that age, weight, height, exercise, as well as the daily intakes of calcium, phosphorus, protein, energy and sodium were the main factors related to OSI in young women. Positive associations were observed between the OSI and the weight, exercise and daily intakes of calcium, protein and energy, whereas while negative associations were seen between the OSI and the age, height and daily intakes of phosphorus and sodium. In addition, all of these factors were also independently related to the OSI.

We investigated whether amino acid substitution of tryptophan by arginine at the residue 64 (64 Arg) of beta 3-adrenergic receptor affects on the degree of reduction in the abdominal fat distribution during a 3-month weight reduction program in either pre- or postmenopausal Japanese women. Beta 3-adrenergic receptor gene polymorphism was examined in 90 Japanese obese women by restriction-enzyme cleavage conformation. The visceral and subcutaneous fat area was measured by magnetic resonance imaging. The baseline body mass index, body weight, fat mass and abdominal subcutaneous and total fat area in 15 obese postmenopausal women with a beta 3-adrenergic receptor (64 Arg) were significantly higher than those in 25 postmenopausal obese women with a beta 3-adrenergic receptor (64 Trp/64 Trp). In contrast, no such differences were found in the 50 premenopausal obese women. After a 3-month weight reduction period, the ratio of visceral to subcutaneous fat areas tended to be lower in both pre-and post-menopausal women with a beta 3-adrenergic receptor (64 Arg), but statistically significant in only the premenopausal obese women (p

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.

The serum cholesterol level at a young age is considered to be a significant factor in the high prevalence of coronary heart disease. Seven hundred and ninety-six females, mean age 18.9 (18∼22), participated in both blood sampling and a nutritional survey. The nutritional survey was carried out in 1995 by the 24-hour recall method to determine the individual food consumption. The BMI, serum total cholesterol, HDL-cholesterol and triglyceride were 20.8 (SE 0.08) kg/m 2 , 181 (SE 1.0) mg/dL, 60 (SE 0.4) mg/dL, 66 (SE 1.2) mg/dL, respectively. Higher than normal levels of total cholesterol (>200 mg/dL) and Lp(a) (>30mg/dL) were obtained in 22.1% and 19.3% of the subjects, respectively. The total energy intake was 1700 kcal/day, twenty-seven % of which was derived from fat and 46% from cereals. In a multiple regression analysis, the serum total cholesterol and LDL-cholesterol were found to be significantly associated with the BMI as well as the simple carbohydrate and fat energy ratio, respectively, whereas the HDL showed a significantly negative correlation with the BMI. The triglyceride level was associated with the BMI. These results suggests that the BMI, fat energy ratio and simple carbohydrate intake, such as cakes and beverages, appear to be the main factors influencing of hyperlipidemia in young Japanese females.

We examined whether or not the oral administration of L-nitroarginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, promotes cholesterol-induced arteriosclerosis in the aorta and the coronary artery. Thirty-six male Japanese white rabbits were fed 0.5% cholesterol-containing laboratory chow and randomly assigned to the following three groups: (1) water, (2) 80 microg/ml L-NAME and (3) 400 microg/ml L-NAME in drinking water. The rabbits were fed a 0.5% cholesterol-containing diet for 8 months. During the 8-month period, the concentration of total cholesterol and L-nitroarginine in the serum and the mean blood pressure were measured. The concentration of NO3 in the serum was also measured. After sacrifice, the aortic surface involvement (AI%), the ratio of the thickened intima to the media and the contents of the total cholesterol of the aorta, the maximum % stenosis of the subepicardial large coronary artery, the % frequency of the nearly completely occlusive distal small coronary artery and the area of the myocardial fibrosis were all measured. We found no statistical difference among the three groups regarding the degree of arteriosclerotic lesions of the aorta and of the large coronary artery, and the area of myocardial fibrosis, as well as the serum cholesterol exposure index (the area under the curve of the serum total cholesterol concentration) and the mean blood pressure. However, the serum concentration of L-nitroarginine was approximately 50 and 200 microM/l in groups 2 and 3, respectively. The concentration of NO3 in the serum in group 1 was significantly higher than that in groups 2 and 3. We thus conclude, that the oral administration of L-NAME in the rabbits fed a cholesterol-containing diet for 8 months failed to promote arteriosclerotic lesions in the aorta and the coronary artery, even though the serum concentration of L-nitroarginine increased sufficiently to inhibit NO synthase in the arterial endothelium and the NO3 concentration in the serum decreased in the rabbits given L-NAME.

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.

The aim of the present study is primarily to re-examine an animal model of acute myocardial infarction (AMI) and arterial thrombosis, developed by Constantinides and his colleagues in the 1960s, in both heritable hyperlipidemic rabbits and normal rabbits because they did not study these rabbits. The groups in this study consisted of 29 normal rabbits and 29 Watanabe heritable hyperlipidemic (WHHL) rabbits. These rabbits were administered Russell's viper venom (RVV) as a procoagulant, intraperitoneally with serotonin or angiotensin II or saline, intravenously. As a control, 10 normal and 17 WHHL rabbits were administered intravenously with either angiotensin II or saline. These treatments were given on 2 successive days. AMI lesion was found in 8 of 29 normal and 7 of 29 WHHL rabbits receiving RVV and angiotensin or serotonin. Angiotensin II promoted the incidence of aortic thrombosis associated with segmental medial necrosis and an intimal disruption in WHHL rabbits receiving RVV. In the normal rabbits, angiotensin II in addition to RVV induced segmental medial necrosis of the aorta, but angiotensin II alone did not. Thus, we postulated that a synergistic effect of RVV as a cytotoxic substance and a sudden increase in the aortic wall tension by angiotensin II might thus result in acute aortic medial necrosis. The conclusion was that no close correlation between coronary arteriosclerosis and AMI was found in this animal model. The intravenous administration of angiotensin promoted aortic medial necrosis even in normal rabbits treated with RVV and then accelerated aortic thrombosis in the WHHL rabbits treated with RVV.

To investigate the causal relationship between lesions of either the proximal large or the distal small coronary arteries and myocardial fibrosis, the hearts and the aortas of 99 cholesterol-fed rabbits with either intermittent or continuous hyperlipidemia for 8 months or more, 44 Watanabe-heritable hyperlipidemic (WHHL) rabbits and 20 normal rabbits were studied histologically. The size and location of the myocardial fibrosis correlated closely with the almost completely occlusive distal small coronary artery which mainly consisted of macrophages, necrosis and calcification but did not correlate with the maximum % stenosis of the large proximal subepicardial coronary arteries in the cholesterol-fed-rabbits. Myocardial fibrosis and almost completely occlusive lesions of the distal small coronary arteries were very rare in the WHHL rabbits, and the maximum % stenosis of the proximal coronary artery and aortic lesions in the WHHL rabbits tended to be greater than those in the cholesterol-fed rabbits. Thus, we are still not certain as to whether or not, the organic stenosis of the subepicardial coronary artery is responsible for myocardial fibrosis in WHHL-rabbits. In conclusion, a causal relationship was observed between myocardial fibrosis and the occlusive lesions of the distal small coronary arteries in cholesterol-fed rabbits, while the arteriosclerotic lesions of the small coronary artery in cholesterol-fed rabbits completely differed from those observed in WHHL-rabbit.

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.

Objective: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Gottingen miniature pigs. Methods: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. Results: The percent reduction in coronary diameter evoked with 10 μg · kg−1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 ( P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 μg · kg−1)-induced vasoconstriction was also augmented but to a smaller degree \[47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2 [52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) ( P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) μm] than at the denuded sites without X-irradiation [group 2, 58(5) μm\] ( P < 0.05). Conclusions: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

The behavioral changes associated with seizures induced by auditory stimulation in magnesium (Mg)-deficient rats originate in deep brain structures and secondarily project to neocortex. In the present study, we examined the roles of N-methyl-D-aspartate (NMDA) receptors in this seizure model. The intraperitoneal administration of the competitive NMDA receptor blocker DL-2-amino-7-phosphonoheptanoic acid (36 and 72 mg/kg) and the non-competitive NMDA receptor blocker MK-801 (1.35 and 2.7 mg/kg), completely prevented the induction of seizure and bradyarrhythmia or sudden death resulting from seizure. Therefore, the white-noise-induced seizures in Mg-deficient rats are linked to increased neuronal excitability via the NMDA receptor.

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

The effects of intracoronary-administrated endothelin-1 on coronary hemodynamics and regional myocardial function were studied in anesthetized open-chest dogs. Epicardial coronary diameter (CoD) and coronary blood flow (CBF) were measured by a sonomicrometer of 10 MHz piezoelectric crystals and an electro-magnetic flow probe on the left circumflex coronary artery (LCX). Regional wall motion was sonomicrometrically measured at regions supplied by the LCX and left anterior descending artery (LAD) and electrocardiograms were recorded. Endothelin-1, administered as a bolus injections into the LCX via an intracoronary cannula, in a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose of 300 pmol was 12.3 +/- 1.5% (P less than 0.01) and 86 +/- 5% (P less than 0.01), respectively, of the control. The extent of CBF reduction and deterioration of systolic wall motion were linearly related with the dosage of endothelin-1. ST-elevation (lead II) and fatal ECG abnormalities, including complete atrioventricular block or ventricular fibrillation, were observed with doses above 60 and 100 pmol, respectively. Coronary angiography revealed that filling defects of dye were propagated from the third or distal branches to those of more proximal arteries when the doses of endothelin-1 were cumulatively infused into the LCX. Accordingly, lethal myocardial ischemia induced by endothelin-1 is produced by critical obstruction of rather small coronary vessels.

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.

A noninfarcted, entirely collateral-dependent myocardial region provides an opportunity to assess the effect of nitroglycerin on coronary collateral function during exercise. Stress thallium-201 computed tomography was performed in seven patients with effort angina and no history of myocardial infarction, both before and after nitroglycerin (0.3 mg). All patients had single-vessel disease with total or subtotal (99% with delay) occlusion of proximal left anterior descending coronary artery and well-developed collaterals. The pressure-rate product, mean blood pressure, and heart rate at peak exercise did not differ before and after nitroglycerin. The size of the perfusion defect and the severity of ischemia during exercise estimated by quantitative analysis of thallium-201 single photon emission computed tomography were significantly less after nitroglycerin administration (extent score: 23 +/- 17 vs 7 +/- 9, p less than 0.01; severity score: 20 +/- 22 vs 3 +/- 4, p less than 0.05). The pressure-rate products at peak exercise did not differ before and after nitroglycerin, which suggested that the reduction in perfusion defect size was unlikely to be the result of decreased myocardial oxygen consumption. These results suggest that nitroglycerin improved coronary collateral function during exercise and thus prevented exercise-induced myocardial ischemia.

We continuously observed successive pairs of R-R intervals during atrial fibrillation and hypothesized that the shortest R-R interval for a given preceding R-R interval in a pair represents the functional refractory period of the atrioventricular node at that preceding interval. To test this hypothesis we simulated atrial fibrillation in 28 isolated cross-perfused canine hearts and obtained an R-R interval scatterplot by plotting the R-R intervals as a function of the immediately preceding R-R interval. This scatterplot enabled us to detect a series of the shortest R-R intervals for a wide range of preceding R-R intervals, and this allowed us to estimate the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation. The estimated functional refractory periods correlated well with those measured by the conventional method (r = 0.93). We conclude that the proposed method makes it possible to estimate the rate-dependent functional refractory periods of the atrioventricular node in atrial fibrillation.

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.

It is not known whether hypertrophic cardiomyopathy (HCM) is accompanied by an abnormality in vascular smooth muscles. In this study, we examined the maximal vasodilator capacity of forearm resistance vessels by measuring minimal forearm vascular resistance (min. FVR) during peak reactive hyperemia after 10 min of arterial occlusion in patients with HCM (n = 15, 41 +/- 4 years old) and age-matched control subjects (n = 12, 42 +/- 3 years old). Forearm blood flow (FBF) was measured by a mercury-in-silastic strain gauge plethysmograph and FVR was calculated by dividing mean blood pressure by FBF. Resting FBF was lower (P less than 0.05) and resting FVR was higher (P less than 0.01) in patients with HCM than in control subjects. Min. FVR was significantly greater in patients with HCM than in control subjects (2.7 +/- 0.2 vs 1.5 +/- 0.2 units, P less than 0.005). We also examined vasoconstrictive responses to intra-arterially infused angiotensin II (20 and 40 ng/min); responses were greater in patients with HCM than in control subjects (P less than 0.05). These results indicate that forearm circulation is altered in patients with HCM. The result that the maximal vasodilator capacity of forearm resistance vessels is limited in patients with HCM as compared with that in age-matched control subjects suggests that there may be abnormalities in forearm resistance vessels in patients with HCM, which might involve increased wall thickness or intrinsic abnormalities in vascular smooth muscle.

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.

A successive RR interval plot was developed to analyze arrhythmia. The plot consisted of a set of points with the x-value of (N)th RR interval and the y-value of (N + 1)th RR interval. This method was applied in the arrhythmia analysis of Holter electrocardiograms obtained from 35 patients. In the analysis of ventricular premature contractions (VPCs) this method was useful not only in detecting VPCs but also in demonstrating coupling interval-dependent characteristics of VPCs. In the analysis of atrial fibrillation the successive RR plot enabled the authors to estimate the functional refractory period of the atrioventricular conduction. In conclusion, despite its simplicity, the successive RR plot was found to be powerful in analyzing arrhythmia. Specifically, the potential to analyze integrally the coupling interval-dependent properties of various types of arrhythmia makes it attractive as a clinical tool.

To clarify the incidence and clinical characteristics of exercise-induced myocardial ischemia in patients with vasospastic angina, we performed exercise thallium computed tomography in 25 patients who had no significant coronary artery stenosis greater than 70%. Coronary artery spasm was documented by coronary angiography in all patients. Eleven patients (44%) developed exercise-induced perfusion defects, but only four of them had anginal pain (36%). Diltiazem (90 mg, administered orally) prevented the development of exercise-induced perfusion defects in all patients. Multivessel coronary spasm was documented by coronary angiography in 11 patients, and nine of them (82%) showed exercise-induced perfusion defects (p less than 0.05).(1) Exercise-induced myocardial ischemia was demonstrated in 44% of patients who had vasospastic angina without fixed coronary stenosis, and 64% of them were asymptomatic. (2) Patients with multivessel spasm had a greater prevalence of exercise-induced myocardial ischemia than those with single-vessel spasm.

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.

The effects of magnesium deficiency on epinephrine-induced ventricular tachyarrhythmia were investigated in adult rats. Forty-two adult Wistar rats were fed a magnesium-deficient diet while 30 rats were fed a standard diet for 20 days. The plasma magnesium concentration was lower in the magnesium-deficient rats (0.22+/-0.01 mmol/l) than in the control rats (0.76+/-0.03 mmol/l, P < 0.001). Using a telemetry system, electrocardiograms and arterial blood pressure were recorded on a polygraph in an unrestrained condition. Epinephrine was infused intravenously starting at 5 microg/kg per minute. The QT interval was prolonged to 50+/-1 ms in the magnesium-deficient rats compared with 44+/-1 ms in the control rats (P < 0.001). Before the administration of epinephrine, no ventricular tachyarrhythmias or seizures were found in either the control or the magnesium-deficient rats. The incidence of epinephrine-induced sustained ventricular tachycardia (VT) was higher in the magnesium-deficient rats (86%) than in the control rats (43%, P < 0.01). However, this VT did not result in sudden death. Seizures always preceded death in both the magnesium-deficient and control rats while the arrhythmias observed immediately before death were mainly bradyarrhythmias. The present study in an adult rat magnesium-deficient model revealed that magnesium deficiency enhances the susceptibility to epinephrine-induced ventricular tachyarrhythmias.

We herein describe three siblings with familial amyloid cardiomyopathy in a Japanese family, who demonstrated an Ile-50 mutation in the transthyretin gene. In their clinical course, the symptoms started at from 50 to 55 years of age, and two cases died within 5 years. However, one case is still alive seven years after onset probably due to either the implantation of a pacemaker for a complete atrio-ventricular block or the administration of dimethylsulphoxide. Based on our findings, some differences were observed not only in the mutation of the transthyretin gene but also in the clinical course between our cases and the previously reported cases.

To clarify malignant arrhythmias in magnesium (Mg) deficiency, we used weanling rats in study 1 and an adult rats in study 2. In study 1, weanling rats were fed either an Mg-deficient diet or a control diet for approximately 2 weeks and then electroencephalogram (EEG) and electrocardiogram (ECG) were recorded during auditory stimulation until death. EEG changes were abrupt attenuation of EEG background activity at the onset of tonic convulsion and then spike-wave complex at the falling down stage in association with marked bradyarrhythmias. When flattening of EEG became after generalized seizures, death occurred within a few minutes but consistent ventricular tachyarrhythmias were not observed. NMDA receptor blockers given intraperitoneally prevented significantly seizure occurrence and sudden death. These results may suggest that sudden death in weanling Mg-deficient rats results from a neurologic trigger.

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.

Objective: The aim was to elucidate the contribution of atheromatous plaque to alterations of smooth muscle contraction to vasoconstrictive agents, by examining vasoreactivity of vascular smooth muscle from the thoracic aorta of 10-13 month old Watanabe heritable hyperlipidaemic rabbits. Methods: From the same vascular ring of the lower thoracic aorta, a pair of small medial smooth muscle strips was prepared from the sites beneath the atheroma (atherosclerotic medial muscle strip) and from those beneath the plaque-free intima (normal medial muscle strip), and isometric tension was measured. Results: Contractions to 118 mM KC1, histamine (30 nM to 10 μM), and noradrenaline (3 nM to 0.3 μM) were similar between atherosclerotic and the normal medial muscle strip. The ED50 to serotonin was 49(SD 28) and 116(66) nM (p

In order to elucidate the mechanism of behavioral alterations in magnesium-deficient rats, changes in the electroencephalogram (EEG) and electrocardiogram (ECG) were studied during auditory stimulation and correlated with the behavioral alterations. Weanling rats were fed either a Mg-deficient diet or a control synthetic diet for 2-3 weeks before the experiment. EEGs were recorded from the hippocampus and the sensorimotor and auditory cortices, and ECGs with a telemetry system. White noise with an intensity of 100 dB was given continuously to induce behavioral changes. The Mg-deficient rats developed consistent and graded behavioral changes in response to the stimulation, showing running-jumping behavior (stage 1), followed by tonic limb convulsion (stage 2) and finally by falling down on the floor (stage 3). The EEGs also showed consistent changes with spike activity, initiating in the hippocampus (stage 2) and then spreading to the neocortices bilaterally (stage 3). These findings indicate that the behavioral changes induced by auditory stimulation in the Mg-deficient rats are due to seizures arising in deeper brain structures, particularly in the limbic system, and projecting secondarily to the neocortices. The ECG changes, mainly consisting of marked bradyarrhythmia, occurred as early as the appearance of the EEG spikes, indicating that they were also related to the seizure. We conclude therefore that Mg deficiency in rats causes increased excitability of the central nervous system, resulting in seizures possibly originated in the limbic system, later developing secondary generalization, and also causing cardiac dysfunctions.

Pathogenesis of the so-called “heart attack” still remains to be elucidated. The links between stable effort angina and unstable or acute myocardial infarction, and between asymptomatic and spontaneous angina are all missing. In medicine presently, pathophysiology of ischemic heart disease is considered a consequence of i) the progression of atherosclerotic narrowing of the coronary artery, and ii) dynamic and transient obstruction (coronary spasm), but these mechanisms are traditionally believed to be unrelated. This article demonstrates various experimental evidence indicating that these two mechanisms are related. And, this review article describes how to produce experimental coronary spasm in the presence of atherosclerosis, similar to that seen in patients with variant angina, and that coronary spasm can produce sudden progression of coronary atherosclerotic obstruction due to intramural hemorrhage. Establishment of various animal models to elucidate mechanisms related to various stages of ischemic heart disease are needed.

Coronary spasm plays an important role in variant angina, effort angina, acute myocardial infarction, and/or sudden death [1–4]. Augmented responses of the coronary artery to vasotonic agents have been documented angiographically in patients with variant angina; however, the mechanisms of enhanced luminal narrowing remain unclarified, both clinically and experimentally. In order to elucidate factors involved in the enhanced responses of the coronary artery, we developed an animal model with the following features [5,6]: (1) transient changes in coronary diameter can be assessed angiographically, (2) coronary spasm can be repeatedly provoked, and (3) myocardial ischemia at the area distal to the site of the stenosed coronary artery can be documented. We chose Gottingen miniature swine as an animal model of coronary spasm [5], because (1) repeated examinations of coronary angiography and endothelial balloon-denudation were feasible using a catheterization technique and (2) pigs seem to be the most appropriate animal model for inducing atherosclerosis by changes which occur that closely resemble those seen in humans. We used mainly coronary arteriography for documentation of spastic events, because this technique is the only available tool for determining regional differences in vascular responsiveness to vasoactive substances in situ [6]. Regional intimai thickening along the left coronary artery was produced to mimic the diseased state of humans, this being the area in which the endothelial denudation had been one of procedures for inducing atherosclerotic lesions in experimental animals [7,8].

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.

Norepinephrine, epinephrine, and 5-hydroxytryptamine (5-HT) modulate the vascular tone via specific receptors on the vascular wall. Binding characteristics and localization of alpha-adrenergic and serotonergic receptors were determined in porcine aortas and coronary arteries. Radioligand binding studies were done using frozen sections of vascular tissue (10 microns thick), and the obtained data were compared with findings on microsomal fractions prepared from smooth muscle cells. Affinities [dissociation constant (Kd)] of 125I-labeled 2-[beta-(4-hydroxyphenyl)-ethylaminomethyl]-tetralone (BE 2254), an alpha 1-antagonist, for alpha-adrenergic receptors on aortic and coronary microsomal fractions were 190 and 224 pM, respectively. The Kd of 125I-labeled lysergic acid diethylamide (LSD), a serotonergic antagonist, to serotonergic receptors on the aorta was 403 pM, a value less than that obtained for the coronary artery (873 pM, p less than 0.01). The Kd of 125I-BE 2254 on tissue sections from the aorta was 164 pM and did not significantly differ from that obtained for microsomal fractions. Inhibition constants of adrenergic agonists and antagonists for specific 125I-BE 2254 binding on aortic sections were identical with those obtained for microsomal fractions. Receptor densities examined by 125I-BE 2254 and 125I-LSD were higher in the aorta than in the coronary artery. 125I-BE 2254 bound specifically to alpha 1-adrenergic and 125I-LSD to 5-HT1-like receptors. Radiodensities of 125I-BE 2254 and 125I-LSD were homogeneous macroscopically across the aortic media. Silver grains distributed homogeneously over the smooth muscle cells across the media. There was no accumulation of silver grains to the intima.(ABSTRACT TRUNCATED AT 250 WORDS)

By measuring the 45Ca2+ movement in saponin-skinned primary cultured rat aortic smooth muscle cells, we examined the specificity of the inhibitory effect of heparin on the IP3-induced Ca2+ release. IP3 (100 mumol/l) markedly (98%) decreased the MgATP-dependent 45Ca2+ content in the non-mitochondrial Ca2+ stores in the presence of 1 mumol/l free Ca2+. Heparin (1-100 micrograms/ml) dose-dependently inhibited this Ca2+ release by IP3. In Ca2(+)-free solution, heparin (100 micrograms/ml) inhibited the increases in 45Ca2+ efflux rate evoked by 10 mumol/l IP3. De-N-sulfated heparin did not inhibit the IP3-induced Ca2+ release. Hyaluronic acid, heparan sulfate, chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C and 2,6-disulfated D-glucosamine had no inhibitory effects on the IP3-induced Ca2+ release. High concentrations (over 1 mg/ml) of heparin inhibited the 45Ca2+ influx and decreased the 45Ca2+ content in skinned cells. These results suggest that heparin (1-100 micrograms/ml) specifically inhibits the IP3-induced increase in Ca2+ permeability of Ca2+ stores and that three sulfate groups at different locations on the molecule of heparin, two at the D-glucosamine and one at the iduronic acid, may be important for this action, in skinned vascular smooth muscle cells, in culture.

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.

The present study was designed to develop an animal model of coronary spasm and to elucidate the mechanism and pathophysiology of coronary spasm. We used Gottingen miniature pigs as a model, because provoked coronary hyperconstriction in this animal often accompanied ischemic ECG-ST change 3–6 months after regional balloon denudation of the left coronary artery. Serotonin and histamine, but not phenylephrine, indomethacin, thiothromboxane A2 or leukotrienes LTC4 or LTD4, provoked augmented constriction at the coronary segment(s) with intimal thickening. Topics discussed here include (1) the role of hypercholesterolemia and/or intimal thickening (geometric effect) on coronary spasm, (2) the mechanisms of arterial hypercontraction in the isolated perfused heart, and (3) the roles of endothelial and smooth muscle functions on the genesis of hyperresponsiveness to autacoids.