Carperitide (synthetic atrial natriuretic peptide) is a newly developed drug for the treatment of heart failure. Although this drug has been used for various types of heart failure, it remains unknown whether it has additive effects on hemodynamic parameters or renal excretory function during intensive treatment for acute refractory heart failure. We have examined the cardiorenal and hormonal effects of carperitide (0.05-0.10 μg / min / kg) in 9 patients (mean age: 67±8 years) with severe heart failure complicated with acute myocardial infarction, in which a range of intensive treatments have already been started. Hemodynamic parameters were determined before and 4, 24 and 48 hours after initiation of carperitide. Pulmonary capillary wedge pressure (mean±SD) had decreased dramatically from 21±6 to 11±5 mmHg (p<0.01) 4 hours after the treatment without significant renal effects. Heart rate and systemic blood pressure were not significantly changed. These beneficial effects were maintained for at least 24 hours. Plasma aldosterone levels fell significantly in response to the drug (from 148±68 to 56±29 pg / ml; p<0.05). However, mean hourly urine output remained unchanged after carperitide. In conclusion, intravenous infusion of carperitide promptly and persistently reduces left ventricular filling pressure without diuresis, hypotension, reflex tachycardia, or neurohormonal activation in patients with refractory heart failure due to severe acute myocardial infarction.

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We studied the effects of external copper exposure on plasma copper, serum lipids, lipoproteins and apolipoproteins in workers who have excessive contact with copper. Fifty-eight healthy Turkish males who were working in the copper processing industry and 33 control subjects were examined. Copper concentration was measured by flame atomic absorption spectrometry, lipid and lipoprotein levels were detected by spectro- photometry and apolipoproteins were measured with a nephelometer.
There was no significant difference in plasma copper between the workers and the controls. However, in the worker group, the mean levels of TC, LDL-C, apoAI, apoB and Lp (a) were significantly higher while the mean level of HDL-C was significantly lower than that of the controls. In addition, there was a significant positive correlation between plasma copper and LDL-C only in the workers group.
Our findings suggest that excessive contact with copper may contribute to coronary risk factors.

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Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown etiology that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. We investigated the relationship between the electrocardiogram (ECG) appearances and signal-averaged ECG (SAECG) in 7 cases with ARVD, and evaluated the usefulness of SAECG as a screening test to detect patients with ARVD. Compared with the conventional 12-lead ECG, the SAECG detects abnormalities at a higher rate in ARVD patients (57% versus 86%). SAECG was more sensitive as a screening test to detect patients with ARVD than 12-lead ECG.

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Normal P wave signal-averaged electrocardiogram (SAE) values were determined in 120 healthy Japanese adults (56 men, 64 women), aged 44.5±10.2 years (mean±SD). The P wave trigger method was used with a Fukuda FDX6500 recorder. We used bipolar Frank leads (X,Y,Z), and recordings were made with forward and backward digital Butterworth filters [40 Hz (18 dB / oct) -300 Hz (12 dB / oct)]. The recordings were taken for the following five parameters: forward and backward filtered P wave duration [fPd (F); fPd (B)]; bidirectionally corrected fPd [fPd (C)]; and 20 ms of the terminal portions of voltage at forward and backward filtering (RMS₂₀). Overall, fPd (F) was 117.8-136.4 ms, fPd (B) 116.4-134.4 ms, fPd (C) 97.4-115.2 ms, RMS₂₀ (F) 1.6-3.6 μV, and RMS₂₀ (B) was 2.2-5.4 μV. Between the sexes, there were significant differences in fPd (F) (p<0.001) and fPd (B) (p<0.01) and in RMS₂₀ (F) (p<0.05) and RMS₂₀ (B) (p<0.05). Weak positive correlations were observed between fPd (F) and body surface area, fPd (F) and age, fPd (B) and body surface area, fPd (B) and age, fPd (C) and body surface area, and fPd (C) and age. There was no evident correlation, however, between either forward or backward RMS₂₀ and body surface area or between forward or backward RMS₂₀ and age. Differences in the normal P wave values between the sexes and age groups were evaluated in this study.

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Previous studies have shown that acute administration of estrogen improves endothelial function in postmenopausal women, but there has been little investigation of the chronic effects of transdermal estrogen replacement therapy. The present study assessed the effect of transdermal estrogen replacement therapy (0.025 mg / day for 4 weeks, the normally applied dosage in Japan) on flow-mediated endothelium-dependent vasodilation of the brachial artery (B-mode ultrasound) and forearm cutaneous blood flow (laser Doppler flowmetry), and plasma hormonal and lipid levels in 12 normolipidemic postmenopausal women. Neither resting vascular diameter, flow-mediated vasodilation, nor time to peak vasodilation, showed significant changes after the estrogen therapy. In contrast, resting forearm cutaneous blood flow decreased significantly after the estrogen therapy. The time to the peak reactive hyperemia in the forearm skin was slightly shortened, and the % change in reactive hyperemia decreased slightly after the therapy. These findings seemed to reflect the inhibition of hot-flush symptoms associated with vasomotor abnormalities in cutaneous tissue. The lack of improvement in flow-mediated vasodilation of the brachial artery despite the inhibitory effect on cutaneous vasomotor abnormalities may be related to the low plasma estradiol concentration obtained with the present transdermal therapy (42.4±15.2 pg / ml), a finding which supports the estrogen threshold hypothesis in hormone replacement therapy.

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Endothelium-dependent vasodilation is impaired in atherosclerosis. Oxidized low density lipoprotein (ox-LDL) plays an important role, possibly through alterations in G-protein activation. We examined the effect of acute exposure to ox-LDL on the dilator responses of isolated rabbit aorta segments. We sought also to evaluate the specificity of this dysfunction for dilator stimuli that traditionally operate through a G_i-protein mechanism. Aortic segments were prepared for measurement of isometric tension. After contraction with prostaglandin F_2α, relaxation to thrombin, adenosine diphosphate (ADP), or the endothelium-independent agonists, sodium nitroprusside (SNP) or papaverine was examined. Maximal relaxation to thrombin was impaired in the presence of ox-LDL (17.7±3.7% p<0.05) compared to control (no LDL) (52.6±4.0%). Ox-LDL did not affect maximal relaxation to ADP or SNP. However, in the presence of charybdotoxin (CHTX: calcium-activated potassium channel inhibitor) ox-LDL impaired relaxation to ADP (17.4±3.2%). CHTX did not affect control (no LDL) responses to ADP (69.6±5.0%) or relaxation to thrombin or papaverine. In conclusion, ox-LDL impairs relaxation to thrombin, but in the case of ADP, calcium-activated potassium channels compensate to maintain this relaxation.

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The influence of coenzyme Q₁₀ (CoQ₁₀) in cold stress test (-15°C for 4 hours) cardiac functional impairment was studied in isolated isovolumic heart of control rats (C; n=12) and of placebo (P; n=11) and treated rats (CoQ₁₀; n=10). In addition, electron microscopic evaluation of left ventricular (LV) slices (n=3 in each group) allowed us to analyze the myocardial ultrastructure. Maximal values of developed pressure (DP_max) were similarly decreased in cold stressed animals (C=129±3.9 mmHg; P=106±6.7 mmHg; CoQ₁₀=91± 3.9 mmHg); however, volume-induced enhancement of pressure generation (slope of DP / volume relations: C=0.248±0.0203 mmHg / μl; P=0.2831±0.0187 mmHg / μl; CoQ₁₀=0.2387 (0.0225 mmHg / μl; p > 0.05), and the duration of systole (C=80±1.6 ms; P=78±1.3 ms; CoQ₁₀=80±2.7 ms) were not altered. Myocardial relaxation, evaluated by the relaxation constant (C=39±1.9 ms; P=42±3.4 ms; CoQ₁₀=51±6.0 ms), as well as resting stress / strain relations were unaffected by cold stress. Myocardial samples showed that pretreatment with CoQ₁₀ attenuates myofibrillar and mitochondrial lesions, and prevents mitochondrial fractional area increase (P: 53.11%>CoQ₁₀: 38.78%=C: 33.87%; p< 0.005) indicating that the exogenous administration of CoQ₁₀ can reduce cold stress myocardial injury.

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The purpose of this study was to clarify whether physiological concentrations of bile acids could affect endothelial nitric oxide production. We investigated the relationships between clinical concentrations of individual bile acids observed in patients with hepatobiliary diseases and endothelial nitric oxide production induced by each bile acid.
Fifteen serum bile acids were measured using high-performance liquid chromato-graphy combined with enzymatic fluorometry in 8 patients with liver cirrhosis, obstructive jaundice, and 8 healthy subjects. The effects of individual bile acids on nitric oxide production were examined in human umbilical endothelial cells by measuring the concentration of NO₂⁻ in the cultured medium. NO release in the blood was also determined by measuring the NO₂⁻ / NO₃⁻ concentration in these patients.
In patients with hepatobiliary diseases, the plasma concentrations of chenodeoxycholic acid, ursodeoxycholic acid and cholic acid (free acid, taurine and glycine conjugates) were markedly elevated. Incubation of cells with chenodeoxycholic acid and deoxycholic acid (free acid, taurine and glycine conjugates) enhanced NO₂⁻ production in a concentration-dependent manner, while cholic acid (free and its conjugates) did not. The effects of individual bile acids on nitric oxide production were additive. Patients with liver cirrhosis and obstructive jaundice had higher plasma levels of NO₂ ⁻ / NO₃⁻ levels than the control subjects.
These results suggest that increased plasma concentrations of chenodeoxycholic acid (free, taurine and glycine conjugates) in patients with hepatobiliary diseases may induce endothelial nitric oxide production. Thus, nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in patients with liver diseases.

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Reversible left ventricular wall motion abnormalities mimicking myocardial infarction have been reported in patients with a noncardiac illness. Their coronary angiograms do not demonstrate organic stenosis or epicardial coronary vasospasm. In this article, two cases of reversible left ventricular contraction abnormality are presented. Electrocardiography showed deep inverted T waves in precordial leads, and the echocardiography revealed diffuse akinesis of the apical region in the acute phase. Coronary angiography showed no significant stenosis or occlusion in either patient. Thallium scintigraphy showed no defect, while the metaiodobenzylguanidine scintigraphy demonstrated significant defects in the apex. The relative coronary flow reserve ratio, measured with an intracoronary Doppler flow wire, was significantly reduced in both patients. Myocardial contrast echocardiography revealed a reversible perfusion defect in the apex in the acute phase in case 2. Transiently impaired coronary microcirculation was thought to be involved in the pathogenesis of the reversible left ventricular dysfunction observed in these patients.

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A 33-year-old Japanese man had an attack of chest pain associated with ST-segment elevation in the inferolateral leads on his electrocardiogram. Emergency coronary angio-graphy showed total obstruction in the mid right coronary artery (RCA) and a movable thrombus in the proximal left anterior descending artery (LAD). We performed emergency percutaneous transluminal coronary angioplasty (PTCA) for the RCA lesion. The operation was successful and we then conducted intracoronary thrombolysis (ICT) with tisokinase 6,400,000 IU for the LAD thrombus. Its size was reduced by ICT. He had an uneventful hospital course. After 1 month, repeat coronary angiography showed no significant stenosis in the RCA nor thrombus in the LAD. A coronary spasm provocation test was performed using acetylcholine. Coronary spasm in the LAD was induced by an intracoronary injection of 100 μg acetylcholine. In this case, we observed a unique condition suggesting simultaneous double coronary artery occlusion.

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A 27-year-old woman with atrial septal defect (ASD) and a sensation of squeezing in the anterior chest by effort was admitted to our hospital. In addition to the ASD, the coronary angiogram showed an abnormal anomalous position of the right coronary artery. Exercise thallium (Tl)-201 cardiac scintigram with an electrocardiogram clearly detected myocardial ischemia in the inferior area. In the operative findings, the orifice of the right coronary artery was positioned high above the commissure between the right and left sinuses of Valsalva, and it ran between the aorta and pulmonary trunk. Considering myocardial ischemia possibly caused by the anomalous origin of the right coronary artery, a coronary artery bypass graft (CABG) was simultaneously performed to the right coronary artery with direct closure of ASD. The myocardial ischemic finding in the inferior area disappeared after the operation, and she was also relieved from the chest pain. In view of these findings, we suggest that an active combination treatment such as CABG and ASD closure is highly successful in a patient with a threatening coronary anomaly and congenital heart disease.

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Primary leiomyosarcomas of the heart, particularly those affecting the right ventricle, are uncommon. We report the case of a 70-year-old Belgian woman presenting with the symptoms of progressive exertional dyspnea and left-sided pleuritic pain. A leiomyosarcoma which originated from the right lateral ventricle wall, causing pulmonary outflow obstruction. was diagnosed. Pathology revealed a neoplasm with a myxoid stroma, high mitotic activity and nuclei expressing atypia. Immunohistochemical staining was positive for vimentine and desmin. Seven months after complete surgical resection the tumor relapsed.
This case demonstrates the poor outcome, the high relapse rate and inefficiency of treatment associated with primary cardiac leiomyosarcomas. The current literature regarding the incidence, diagnostic techniques, treatment strategies and survival rates of this rare but terminal disease is reviewed.

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A metastatic synovial sarcoma of the left ventricle is described. A 26-year-old Japanese woman underwent resection of a synovial sarcoma of the right thigh 8 years prior to admission, which was followed by multiple surgical procedures for pulmonary metastasectomy. Echocardiography demonstrated obstruction of the outflow tract of the left ventricle caused by a metastatic tumor, which was surgically resected on the day of admission. The histologic characteristics of the cardiac tumor were identical to those of the pulmonary metastases. Additional cardiac metastasectomy was performed 9 months later. She complained of dyspnea on exertion 8 months after the second cardiac metastasectomy due to recurrence in the heart. Radiotherapy with LINAC (a total dose: 50 Gy) diminished the size of the tumor temporarily. The patient died 20 months after the initial cardiac metastasectomy.

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