Subarachnoid hemorrhage (SAH) due to aneurysmal rupture is frequently complicated by cardiopulmonary episodes, including sudden death. We investigated the pathogenesis of cardiopulmonary complications from clinical observation of 715 cases with SAH. There was transient left ventricular asynergy in 9.4% (67/715) of the cases, which consisted of mechanical heart failure and myocardial necrosis. Plasma catecholamine concentration was higher in these patients compared with those without left ventricular asynergy. Transient left ventricular asynergy was considered to result from myocardial derangement:“a panic myocardium, ” due to a sudden burst of catecholamine. Concerning arrhythmia in SAH, cases with life-threatening arrhythmia, such as ventricular tachycardia or ventricular fibrillation, had higher concentrations not only of plasma catecholamine but also of serum CK-MB, myosin light chain and troponin T, compared with patients who had no ventricular arrhythmia. This implies that life-threatening arrhythmia in SAH would result from myocardial damage due to catecholamine. We devised a novel animal model of SAH in order to clarify the relation between sympathetic nervous activity and myocardial damage immediately after the onset of SAH. The animal experiments showed that sympathetic nervous activity as well as cardiac contractility were transiently elevated, but cardiac function subsequently declined. Serum CK-MB was increased from the onset of SAH and a high value was maintained throughout the entire experimental period. In conclusion, extraordinary transient enhancement of sympathetic nervous activity induces myocardial damage resulting from what is characterized by “a panic myocardium.”

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Previous studies have reported that high serum lipoprotein(a) levels may be responsible for total occlusion of the infarct-related artery via inhibition of intrinsic fibrinolysis during acute myocardial infarction. We evaluated whether this would result in a greater extent of myocardial necrosis and impaired left ventricular function in patients with high lipoprotein(a) levels. Sixty-eight patients with prior myocardial infarction, who were not receiving thrombolytic therapy underwent coronary angiography and stress-redistribution-reinjection Tl-201 scintigraphy. Antegrade TIMI flow in the infarct-related artery was lower(1.54 ± 1.14 vs 2.15 ± 1.05; p = 0.03) and the collateral index was higher (1.3 ± 1.0 vs 0.8 ± 0.9; p = 0.07) in patients with high lipoprotein(a) levels (> 30 mg/dl) compared to those with low lipoprotein(a) levels (≤30 mg/dl). Regional wall motion score index was lower (0.8 ± 0.8 vs 1.4 ± 0.5; p = 0.008) and global ejection fraction was higher (46 ± 10% vs 40 ± 11%; p = 0.03) in patients with low lipoprotein(a) levels. On SPECT images, the number of non-viable defects was higher in patients with high lipoprotein(a) levels (4.0 ± 2.5 vs 1.9 ± 1.3; p = 0.0002), whereas the number of viable defects was higher in those with low lipoprotein(a) levels(2.5 ± 1.8 vs 1.5 ± 1.3; p = 0.02). We conclude that high lipoprotein(a) levels may prolong the occlusion of infarct-related artery during acute myocardial infarction and lead to a greater extent of myocardial necrosis and impaired left ventricular function.

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Dobutamine stress echocardiography, Tc-99m radionuclide ventriculography(RNVG), and exercise stress testing were performed prospectively in 63 patients with suspected coronary artery disease to compare the values of exercise testing, dobutamine stress echocardiography and RNVG in the non-invasive diagnosis of coronary artery disease. The sensitivities of dobutamine stress echocardiography and RNVG were found to be higher than that of exercise testing (93-62%, p<0.001;83-62%, p<0.05).The sensitivities of dobutamine stress echocardiography and RNVG were similar (p>0.05). There were no differences between the sensitivities of the three techniques in multiple vessel disease (p>0.05). The specificities of dobutamine stress echocardiography and RNVG were higher than that of exercise testing (for both of the tests 86-62%, p<0.05). The diagnostic accuracy of dobutamine stress echocardiography and RNVG were similar (p>0.05). The results of dobutamine stress echocardiography RNVG were concordant with each other in 46 patients (76%, kappa=65%) in sectional analysis. Dobutamine stress echocardiography and RNVG tests were comparable with each other in 85% of the 189 segments(kappa=64%).The expected 5% decrease at peak doses of dobutamine was not detected in stress echocardiography in 25 patients and in RNVG in 26 of the patients. Dobutamine stress echocardiography and RNVG are superior to exercise testing in the diagnosis of single vessel disease and there is no significant difference between the two techniques. When the ejection fraction is considered in dobutamine stress echocardiography and RNVG, it does not make an additional contribution to the diagnosis of coronary artery disease.

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Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 ± 1.01 μmol/l) than in the control subjects (7.05 ± 0.36 μmol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 ± 16.4 ng/l in the control group and 284.3 ± 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 ± 0.58 μg/l and 8.05 ± 0.72 μg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease.

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Electromagnetic noise is rapidly increasing in our environment so electromagnetic interference (EMI) with pacemakers (PM) may become a more important problem despite technological improvements in PM. The aim of this study was to evaluate the kinds of EMI which affect the quality of life of PM patients. The participants (1, 942 Japanese Association for Pacemaker Patients: Pacemaker-Tomonokai) were asked to respond to a questionnaire about their major EMI troubles, and 1, 567 patients (80.7%) responded by mail. The main concerns were from mobile telephones (MT)(39%), magnetic resonance imaging (MRI)(17%), electronic kitchen appliances, automobile engines and high voltage power lines. If possible, PM implantation sites should be carefully selected not only according to the physician's convenience but also considering information on each patient's habits and physical limitations.

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This study was designed to elucidate whether left precordial negative T waves are electrocardiographic indicators for the diagnosis of hypertrophic cardiomyopathy (HCM) even in the presence of complete right bundle branch block (CRBBB). In 7 consecutive patients with CRBBB accompanied by negative T waves in at least one of the left precordial leads (V4, V5, V6, maximal negativity; 1.06±0.40mVol)(left precordial negative T wave group) and in 15 randomly selected CRBBB patients without left precordial T wave inversions (control group), echocardiography was performed to rule out underlying diseases causing left ventricular overload and to identify candidates for magnetic resonance (MR) imaging. None had anginal pain indicating ischemic heart disease. When 2-dimensional echocardiography indicated left ventricular hypertrophy with wall thickness ≥15mm, the magnitude and distribution of hypertrophy were scrutinized on contiguous left ventricular MR short-axis images. The diagnostic criterion of HCM was the demonstration of hypertrophy with a wall thickness of 20mm or more on the left ventricular MR short-axis images. All patients in the left precordial negative T wave group had negative T waves in both I (negativity; 0.27±0.17mVol) and aVL (negativity; 0.23±0.14mVol), whereas none in the control group did. The diagnostic criterion for HCM was fulfilled in six patients in the left precordial negative T wave group. However there were no patients who fulfilled the criterion in the control group. Negative T waves were recorded in the I (negativity; 0.30±0.17mVol), aVL (negativity; 0.25±0.14mVol), V4 (negativity; 1.03±0.46mVol), V5 (negativity; 0.83±0.37mVol) and V6 leads (negativity; 0.31±0.31mVol) in all patients with HCM, while they were recorded in only 6% of the patients without HCM. In conclusion, the existence of left precordial negative T waves in the presence of CRBBB strongly indicates HCM.

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Global left ventricular (LV) diastolic function has been reported to be disturbed under conditions of right ventricular pressure overload (RVPO). However, from the standpoint of regional wall motion, only a little information related to the mechanism of LV diastolic dysfunction is available. Eight patients with RVPO and 7 healthy volunteers were investigated using tagged cine magnetic resonance imaging. Regional diastolic fraction (RDF) was determined in 4 segments (anterior, lateral, inferior, and septal) in the mid-ventricular short axis section and in 2 segments (septal and lateral) in the 4-chamber section. A heterogeneity index was obtained from the RDFs of the short axis section. In the RVPO group, in both short axis and 4-chamber sections, the RDF of the septal segment was depressed, and it showed an inverse correlation with the right-to-left ventricular systolic pressure (RV/LV) ratio (r = -0.74, p < 0.05) in the short axis section. In the 4-chamber section, the RDF was lower in the septal segment than in the lateral segment (p < 0.05). The heterogeneity index in the RVPO group was greater than that in the control group (p < 0.01). The index correlated positively with the RV/LV ratio (r = 0.77, p < 0.05). The altered regional diastolic motion results in increased heterogeneity in regional diastolic motion.

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An augmented expression of mRNA for IgG light chain was demonstrated age-dependently on atheromatous lesions of the aorta in Watanabe heritable hyperlipidemic (WHHL) rabbits. The present study was designed to determine factors related to inflammation in human vessels excised during surgery. We detected IgG mRNAs using RT-PCR in human atherosclerotic lesions but not in human umbilical arteries which have no atheromatous lesions. To determine the clonality of IgGs, cDNAs encoding variable regions of IgG heavy chain were examined using RT-PCR. Atherosclerotic lesions had several subtypes of IgG gene families' suggesting the involvement of polyclonal B-cells. mRNAs of interleukins-6 (IL-6), -1α (IL-1α), and -1β (IL-1β) were also detected in the same samples. In summary, inflammatory reactions were present in the atherosclerosis lesion.

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Atherosclerosis is a generalized process that may involve the entire vasculature as well as the coronary arteries. Aortic atherosclerosis (AA) is associated with an increased risk for recurrent ischemic stroke and cardiovascular death and can be diagnosed by transesophageal echocardiography (TEE). We performed TEE in 60 patients (47 men and 13 women; age range 37-78, mean 53.5 ± 9.9) who underwent coronary angiography, to assess whether artherosclerosis in the thoracic aorta correlates with coronary artery disease (CAD) or may be a marker for it. Significant CAD was defined as either > 50% reduction of internal diameter of the left main coronary artery or > 70% reduction of the internal diameter in the anterior descending, right coronary or circumflex artery. The number of diseased vessels was based on the Coronary Artery Surgery Study criteria. A grading system was used to detect AA. The thoracic aorta was considered to be normal and classified as grade I when the internal surface was smooth and without lumen irregularities or increased echo-intensity. Grade II changes consisted of increased echodensity of the intima without lumen irregularity or thickening. Grade III changes consisted of increased echodensity of intima with well defined atheroma extending < 3 mm in the aorta. Grade IV and V changes consisted of atheroma > 3 mm and protruding mobile plaques, respectively. Grades III-V were considered as AA. Twenty two of the 29 patients (75.9%) with CAD and 10 of the 31 patients (32.3%) without CAD had AA detected by TEE. There was a significant relationship between CAD and AA (r=0.44, p < 0.001). The sensitivity and specificity of AA in detecting CAD were 75.9% and 67.7%, respectively. Our data suggest that AA is common in patients with significant CAD. Detection of AA by TEE may be a marker for CAD and early detection of aortic atherosclerosis may contribute to diagnostic and therapeutic interventions and thereby improve the prognosis.

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It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Timevelocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId+TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (γ=0.57) between the endo/epi aratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.

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Thromboxane A2 (TXA2) after vascular injury plays an important role in the process of restenosis. S-1452, a potent and selective TXA2 receptor antagonist, blocks the receptors of vascular smooth muscle cells (VSMC) as well as platelets. The purpose of this study was to determine whether S-1452 could reduce platelet deposition and intimal hyperplasia in vascular injury models. New Zealand White Rabbits (n = 41) were fed a 0.5% cholesterol diet. For the short-term study, eighteen rabbits after balloon injury of iliac artery were assigned to 3 groups; systemic administration of S-1452, single local administration of S-1452 using a local delivery balloon, and single local administration of saline solution. Platelet deposition in injured artery using ¹¹¹In-labeled platelets was reduced by 50% in systemic administration and by 60% in local administration compared to saline infusion. For the long-term study, balloon injury of the iliac artery was performed 4 weeks after starting the 0.5% cholesterol diet. Twenty-three rabbits were classified into 4 groups; systemic administration of S-1452, oral placebo administration, single local administration of S-1452, and local administration of saline solution (control group). The platelet aggregation induced by U-46619 was significantly lower in the S-1452 group than in the control group. Systemic administration of S-1452 significantly reduced the intimal area (152 ± 33 vs 735 ± 135 μm², p < 0.001) and number of cells in the intima (513 ± 57 vs 993 ± 57, p < 0.01) compared to controls. In contrast, a single local administration failed to reduce neointimal thickness. Systemic administration of S-1452 reduced intimal hyperplasia as well as platelet deposition in a rabbit injury model, but its single local administration inhibited only platelet deposition.

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Left ventricular hypertrophy (LVH) is a secondary adaptation to increased external load. Various qualitative and quantitative changes in myocytes and extracellular components occur during the development of LVH. It has recently been demonstrated that α-smooth muscle actin (α-SMA)-expressing myofibroblasts appear in the interstitium of the heart subjected to increased workload suggesting that cardiac fibroblasts as well as myocytes alter their phenotype in response to pressure overload. In the present study, to explore the load-induced response and phenotypic modulation of cardiac fibroblasts, the localization of embryonic smooth muscle myosin heavy chain (SMemb) and α-SMA in thoracic aorta-constricted rat hearts was investigated by immunohistochemistry, and the morphology of the SMemb-expressing cells was examined by electron microscopy. In addition, to clarify the mechanisms by which SMemb is induced in pressure-overloaded hearts, mRNA expression of SMemb in aorta-constricted rat hearts and in transforming growth factor-β1 (TGF-β1)-treated or mechanically-stretched cultured cardiac fibroblasts was investigated. Enhanced staining of SMemb and α-SMA was detected in the interstitial spindle-shaped cells in the fibrotic lesions of the pressure-overloaded left ventricles by immunohistochemistry. These cells were demonstrated by electron microscopy to have features specific for activated fibroblasts such as serrated nuclei or prominent rough endoplasmic reticulum. These cells also had characteristic features of myofibroblasts, i.e. irregularly arranged actin filaments and scattered dense bodies. Northern blot analysis revealed increased mRNA levels of SMemb both in aorta-constricted rat hearts and in cultured cardiac fibroblasts stimulated by TGF-β1 or by mechanical stretch. These results suggest that SMemb may be a molecular marker both for the detection of activated cardiac fibroblasts that may play important roles in the remodeling of pressure-overloaded cardiac interstitium, and for the identification of the regulatory mechanisms that control the phenotypic modulation of cardiac fibroblasts in response to pressure overload.

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Hypertrophic cardiomyopathy (HCM) was simulated with a computer heart model having a realistic shape and rotating fiber orientation in order to elucidate possible mechanisms for abnormal ECG findings. The disarray of myocardial muscle in HCM was simulated by assigning random fiber direction and isotropic electrophysiologic properties to abnormal hypertrophic regions, in contrast to the anisotropic modeling for normal myocardium. With these models, main ECG features including abnormal Q wave and QS pattern were reproduced and were comparable with clinical findings. This study suggests that the change in anisotropy in the hypertrophic myocardium is likely to be the main factor responsible to the ECG features of HCM.

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A 55-year-old Japanese man was hospitalized for palpitations and severe chest oppression one hour after he ingested about 1500 ml of beer and sildenafil (Viagra) 50 mg. At 43 years of age, he had been diagnosed with intermittent WPW syndrome following a paroxysmal supraventricular tachycardia (PSVT) attack. He took a 1 mg tablet of doxazosin daily for mild hypertension. On admission, his blood pressure was 90/54 mmHg and his heart beat was weak and irregular with a rate of about 220/min. Since atrial fibrillation (Af) was diagnosed on an electrocardiogram (minimum RR interval; 0.22 seconds), direct current shock was performed with 100 joules and 150 joules but conversion to sinus rhythm failed. Sinus rhythm returned spontaneously from Af four hours after taking sildenafil. Since blood pressure was 50/17 mmHg despite the return to sinus rhythm, blood pressure was maintained by dopamine for twelve hours after sinus rhythm returned. The patient underwent catheter ablation for curative therapy and thereafter has not had any further episodes of tachycardia.

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Symmetric left ventricular hypertrophy or asymmetric septal hypertrophy associated with pheochromocytoma simulating hypertrophic obstructive cardiomyopathy have been rarely reported. In this report, we present a case with pheochromocytoma that had dynamic left ventricular outflow tract obstruction without asymmetric septal hypertrophy. A surface echo revealed resolution of the sytolic anterior motion of the mitral valve and all Doppler evidence of left ventricular outflow tract obstruction following removal of the tumor. Dynamic left ventricular outflow tract obstruction seen in this patient was probably due to excessive secretion of cathecolamines by the tumor.

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