Coronary thrombosis has been implicated in the pathogenesis of acute coronary syndromes, and platelet activation plays a pivotal role in the pathogenesis of coronary thrombus. A new platelet aggregometer using a laser-light scattering beam was trialled for assessment of platelet aggregation. Platelet aggregability, especially small-sized platelet aggregates, was investigated on admission using the laser-light scattering method and again after treatment in 23 patients with acute coronary syndromes. The platelet aggregability in 14 patients with stable exertional angina and in 14 control subjects was also examined. On admission, the number of small- and medium-sized platelet aggregates in the acute coronary syndromes group was significantly greater than in the stable exertional angina group or control group. However, the number of large-sized platelet aggregates on admission was not increased in the acute coronary syndromes group. Furthermore, the number of small- and medium-sized platelet aggregates decreased significantly after treatment in the acute coronary syndromes group. The increased number of small-sized platelet aggregates may sensitively reflect attacks of thrombosis in patients suffering acute coronary syndromes.

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In Japan, data on the epidemiological and clinical features of atrial fibrillation (AF) are rather sparse; even less data are available on the risk of thromboembolism in nonvalvular AF. The present study enrolled 19, 825 patients who visited the cardiovascular clinics of the 13 hospitals in Hokkaido, Japan, between March and July 1995. The prevalence of AF, the clinical characteristics of AF patients, and the occurrence of ischemic events were examined during the 2 year follow-up period. The prevalence of AF increased with age, and the overall prevalence was 14%. Antithrombotic therapy was used in 57% of AF patients and the incidence of ischemic events during the follow-up period was 4.6% in all AF patients. Warfarin reduced the risk of ischemic events in both the valvular and nonvalvular AF groups. A history of cerebrovascular accidents, advanced age, and the presence of underlying heart disease were each associated with a significantly increased risk of ischemic events in the nonvalvular AF group. These results show a lower incidence of ischemic events and more frequent use of antiplatelet drugs in the nonvalvular AF group. Further prospective studies are needed to determine the best preventive methods for thromboembolic complications in Japanese patients with nonvalvular AF.

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Few studies have investigated the contractility of myocardium with a reverse flow--metabolism pattern; that is, greater uptake of nitrogen-13-ammonia (NH₃) than fluorine-18-fluorodeoxyglucose (FDG) on positron emission tomography (PET). This study examined the contraction thickening represented by count increase in ECG-gated FDG-PET of myocardium with a reverse flow--metabolism pattern during low-dose dobutamine stress. Fifty-four patients with myocardial infarction were studied. Relative NH₃ and FDG uptake (%NH₃, %FDG) and %count increase were measured in 216 apical and 216 lateral segments on ECG-gated FDG-PET. The %count increase during low-dose dobutamine stress was greater in myocardium with a reverse flow--metabolism mismatch pattern than in myocardium with a flow--metabolism mismatch pattern (35.9±25.7% vs 24.6±15.9%, p=0.0221 in apical segments, and 38.4±22.6% vs 27.6±18.4%, p=0.0040 in lateral segments) despite smaller %FDG. A reverse flow--metabolism mismatch pattern should be noted as a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow--metabolism mismatch pattern.

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The present study evaluated the application of quantitative coronary angiography (edge detection algorithm) for the analysis of coronary dissection lesions after balloon angioplasty. Acute and late results were obtained by the edge detection algorithm in 60 patients with 66 dissected lesions (NHLBI types B--C). The edge detection algorithm delineated the border of the true lumen in 32 lesions (group with automated analysis alone, 48.5%) and included the dissection cap in the analysis in 34 lesions in which manual editing was adjuncted (group with manual editing, 51.5%). In both groups, the minimal lumen diameter after balloon angioplasty obtained by initial automated analysis was correlated to that obtained at the 5.3-month follow-up similarly (r=0.554, p=0.0010 for the group with automated analysis alone and r=0.613, p=0.0001 after automated analysis for the group with manual editing). However, additional manual editing reduced the correlation coefficient (r=0.240, p=0.1707) in the latter group. Thus, in terms of predicting long-term patency, it is reasonable to let the edge detection algorithm decide the measurements in types B and C dissected lesions.

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Optimal Doppler recordings of stenotic aortic flow are not always easy to obtain. Therefore, the present study investigated how useful intravenous Albunex injections were for improving the Doppler assessment of pressure gradients for aortic stenosis in 20 consecutive patients who underwent Doppler and left-heart catheterization studies within a 1-week period. Continuous-wave Doppler echocardiography was performed using both a 2.5 MHz duplex and a 1.9 MHz independent transducer before and after Albunex injections. The maximum and mean pressure gradients were calculated from the highest Doppler velocity tracings using the simplified Bernoulli equation. Pullback catheterization pressure tracings from the left ventricle to the ascending aorta were superimposed for determination of the maximum instantaneous and mean pressure gradients. The Doppler-derived peak and mean pressure gradients showed significant underestimation compared with the catheterization gradients (23±17 mmHg and 11±7 mmHg, respectively). However, this underestimation disappeared with Albunex injection (-2±7 mmHg and -1±4 mmHg, respectively). Although the Doppler-derived instantaneous and mean pressure gradients correlated well with the catheterization gradients (r=0.909 and r=0.879, respectively), they became much closer with Albunex (r=0.987 and r=0.963, respectively). The improvements in the Doppler-derived peak pressure gradients were significant from an apical window (n=12, 84-120 mmHg, p<0.001), but less so from non-apical windows (n=8, 84-91 mmHg, p=0.0146). Accordingly, Albunex is most useful for Doppler recordings of stenotic aortic flow available from the apical window, but not less so from other acoustic windows.

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The present study aimed to clarify whether cardiac sarcoidosis causes changes that mimic hypertrophic cardiomyopathy. Eighty-two consecutive patients (35 men, 47 women), who were referred to the Department of Cardiovascular Medicine, with a diagnosis of pulmonary and/or ocular sarcoidosis (average age, 49.5 years, range 20-74), underwent detailed clinical, electrocardiographic, and echocardiographic evaluations; in some patients, right and left heart catheterization, selective coronary artery cineangiography, and right and left endomyocardial biopsies were performed. Over a 15-month period of observation, 6 of these 82 patients (7.3%) were found to have echocardiographic abnomalities: increased thickness of the interventricular septum was found in 4 patients, asymmetric septal hypertrophy in 2, localized septal hypertrophy in 1 and apical hypertrophy in 1 patient. One patient had an ‘ace-of-spades’ deformity of the left ventricle. Cardiac sardoidosis can mimic, and even present as, hypertrophic cardiomyopathy.

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Apoptosis regulates the remodeling of tissue during embryonic development by eliminating unwanted cells and structures. The present study investigated smooth muscle cell (SMC) proliferation and apoptosis in the neonatal ductus arteriosus (DA) during closure. In the DA of 39 swine neonates and 5 autopsy human neonates, apoptosis was detected using in situ end-labeling and electron microscopy, and proliferation was evaluated using proliferating cell nuclear antigen. In swine, apoptosis of SMC was first observed at 24h after birth. After 48h, both apoptosis and proliferation quickly increased and became most prominent at 3 days, mainly in the intima and inner media. From 5 days, both apoptosis and proliferation quickly disappeared, and were present to a minor extent at the 2 weeks after birth. During these processes, there was no sign of inflammation or necrosis. In humans, apoptosis was found in tissue specimens obtained from 2 term neonates who died at 1 and 5 days after birth. These findings suggest that SMC contribute to the functional closure of the DA by active constriction, and soon after, they switch to proliferation and apoptosis, which may contribute to the anatomical closure of the DA.

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The purpose of this study was to determine the anisotropic effects of sodium channel blockers on wavelength (WL) and proarrhythmia. In 18 anesthetized, open chest dogs, a 64-electrode array was placed on the left ventricle and the ventricle was constantly paced. Disopyramide, lidocaine or flecainide was intracoronarily administered. Conduction velocity (θ) and activation--recovery interval (ARI) were measured in the longitudinal (L) and transverse (T) directions. Flecainide markedly decreased θL, but did not alter θT or ARIs in either direction. As a result, the wavelength was significantly shortened only in the L direction. Disopyramide or lidocaine did not show direction-dependent effects on θ or WL. In 3 of 6 dogs with flecainide exposure, ventricular fibrillation (VF) developed. However, no VF occurred with disopyramide or lidocaine. Accordingly, the WL is dependent on the fiber orientation of myocardium. The anisotropic shortening of the WL may explain the character of the proarrhythmia observed with flecainide.

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Cardiac hypertrophy is characterized by increased cardiomyocyte protein synthesis, increased cell volume, and a shift in cardiac-specific gene expression to fetal isoforms. Using neonatal rat cardiomyocytes stimulated with fetal calf serum (FCS) as a model for cardiac hypertrophy, the present study investigated the role of 2 signal transduction pathways, extracellular signal-regulated kinase (ERK) and p70 S6 kinase (p70S6K), in the attendant phenotype changes. FCS evoked both ERK and p70S6K activity, peaking at 20-40 min, and simultaneously increased cardiac myocyte protein synthesis (evaluated by [³H]leucine incorporation and total cellular protein content), cell size (evaluated by morphometry and fluorescence-activated cell sorter analysis) and expression of a fetal isoform of the muscle specific gene skeletal α-actin (SKA). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. PD98059, which inhibited ERK activity, attenuated cardiac-specific gene expression in a dose-dependent manner, but had no influence on protein synthesis or cell size. These results indicate divergent roles for the ERK and p70S6K pathways in the phenotypic changes associated with cardiac hypertrophy.

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The functional role of coronary vascular ATP-sensitive potassium (K⁺ATP) channels in the regulation of coronary blood flow (CBF) has not been determined in chronic heart failure (CHF). To test the hypothesis that K⁺ATP channels contribute to myocardial perfusion in HF, we examined the effects of intracoronary infusion of glibenclamide, an inhibitor of K⁺ATP channels, on basal CBF in control and CHF dogs. CHF was produced in mongrel dogs by pacing the right ventricle for 4 weeks. Under anesthesia, CBF in the left anterior descending coronary artery, other hemodynamic and metabolic parameters, or regional myocardial blood flow were measured. Basal CBF was less in CHF dogs than in controls. Glibenclamide at the graded doses (5, 15 and 50μg·kg^-1·min^-1) decreased CBF in both control and CHF dogs. The percentage decrease in CBF with glibenclamide at 50μg·kg^-1·min^-1 was greater (p<0.01) in CHF dogs than in controls. The greater decrease in CBF with glibenclamide at 50μg·kg^-1·min^-1 was associated with myocardial ischemia. Glibenclamide decreased myocardial blood flow in each sublayer of the myocardium in the 2 groups. These results suggest that the basal activity of coronary vascular K⁺ATP channels is increased in CHF dogs but not in controls. This may contribute to the maintenance of myocardial perfusion in CHF.

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A successful case of human atrial natriuretic peptide (HANP) infusion therapy for a neonate who developed congestive heart failure (CHF) after total repair of total anomalous pulmonary venous connection was performed on the first day of life. Following 14h of HANP infusion at incremental doses of 0.125-0.25μg·kg^-1·min^-1, urine output and hemodynamics dramatically improved. Urine output increased from 1.1 to 10.6ml/h (p<0.0001) and good urinary output (13.0ml/h) was maintained even after discontinuation of the infusion. During the infusion, the heart rate decreased from 166 to 152 beats/min (p<0.0001), and the systemic systolic blood pressure increased from 82 to 103 mmHg (p<0.0001). Central venous pressure was not significantly affected by HANP infusion. This is the first successful case of HANP infusion therapy as the first treatment of post-operative pulmonary hypertension in this age group. This therapy can be used safely and may be useful in neonates with CHF resulting from other causes, but more investigation is needed.

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The first stage of eosinophilic myocarditis is called the necrotizing phase. This stage of eosinophilic myocarditis of unknown cause is often fulminant and rapidly fatal, occurring predominantly in males. Here, we report a case of eosinophilic myocarditis in the acute necrotizing phase occurred without known cause in a 23-year-old Japanese female. Severe diffuse hypokinesis of the left ventricular wall motion (ejection fraction 19.3%), significant concentric edematous thickening of the left ventricular wall (20.1 mm in diastole) and a moderate amount of pericardial effusion (10 mm wide echo free space posteriorly) were revealed by echocardiography. Eosinophils were observed and degranulated eosinophilic cationic proteins were stained with antibody against eosinophilic cationic proteins (EG2) in the myocardial specimens obtained by myocardial biopsy. In spite of its severity, the disease resolved promptly with steroid therapy.

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During admission for investigation of dysphagia, an 82-year-old woman suddenly complained of dyspnea, which was followed by cardiogenic shock. Her symptoms, electrocardiogram, echocardiogram and laboratory data were compatible with an extensive acute anterior myocardial infarction. Emergency cardiac catheterization showed no atheromatous narrowing in any coronary artery. However, the contractions of the left and right ventricles were diffusely and severely impaired, except for some hyperkinesis of the basal area. The asynergy, as well as the abnormalities on the ECG, improved almost to normal by the 35th hospital day. An endomyocardial biopsy from the right ventricle during the acute phase showed atypical myocardial damage with proliferation of fine collagen fibers and small round-cell infiltration including polymorphologic leukocytes. This type of transient cardiac disorder has recently been described in Japan, and is called ‘Tako-tsubo cardiomyopathy’ because of the characteristic appearance of the left ventricular asynergy. In the present case, ventricular asynergy was not limited to the left ventricle, but was also present in the right ventricle.

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Two women with myotonic dystrophy underwent dipyridamole thallium-201 (²⁰¹Tl) myocardial perfusion imaging, after which one patient developed flat T waves in lead I and aV_L, and inverted T waves in leads V_2-6. The other patient developed a nonspecific intraventricular block that progressed to complete left bundle branch block and was associated with chest discomfort. Reversible scintigraphic defects were observed in both women. Although there was evidence that suggested myocardial ischemia on the ECG changes and ²⁰¹Tl scintigraphic findings, coronary angiography demonstrated no significant stenoses in either patient. These findings suggest that microvascular dysfunction may lead to myocardial ischemia and conduction disturbances in patients with myotonic dystrophy.

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An obese 23-year-old man with sleep-disordered breathing and primary pulmonary hypertension (PPH) had been administered oral beraprost sodium, anticoagulant warfarin, and home oxygen therapy, at another hospital as treatment for the PPH, but he had not experienced any symptomatic improvement. The patient had a body mass index of 32.4 kg/m², and complained of fatigue, shortness of breath on exertion, excessive daytime sleepiness, and snoring. Arterial blood gas analysis showed a PaO₂ and a PaCO₂ of 70.9 and 31.2 mmHg, respectively. A polysomnographic study revealed central sleep apnea with an apnea-hypopnea index (AHI) of 29.7 episodes/h. The patient showed improvement of daytime sleepiness after starting nocturnal nasal bilevel positive airway pressure (BiPAP) therapy for the central sleep apnea, but his pulmonary hypertension, measured in the daytime, worsened. The patient died suddenly while walking to the bathroom in the morning 1 month after initiation of BiPAP therapy. It is necessary to consider the possibility of sudden death when nasal BiPAP therapy is given to a PPH patient with central sleep apnea.

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A 56-year-old man suffered from type B aortic dissection associated with the right aortic arch and right descending aorta. The patient was successfully treated by implantation of 2 stent-grafts (a 40-mm Z-stent covered with a 37.5-mm woven Dacron graft) and ligation of the dissected left subclavian artery. A postoperative computed tomographic scan revealed thrombosis of the false lumen and a reduction in the descending aortic diameter.

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A 25-year-old woman with Marfan syndrome in the 37th week of pregnancy was referred for acute chest pain and dyspnea. An emergency Cesarean section was performed because of fetal distress. Intraoperative echocardiography at the end of the Cesarean section showed dilatation of the aortic root and dissection of the ascending aorta. The patient underwent replacement of the aortic root and the ascending aorta on the following day because of uterine bleeding. The postoperative course was uneventful for the mother and her baby.

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A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of ¹²³I-β-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: ¹⁸F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

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The use of mongrel dogs for experimental purposes was recently restricted and this report presents the experience of creating an aortic dissection model in swine. All the swine in group 1 were anesthetized without pentobarbital and the descending aorta was side-clamped during the creation of the aortic dissection. The false lumen of the completed dissection was patent in the long term despite not having the anchoring suture that the previous canine model required to stabilize the opening of the entry tear. All the swine anesthetized with pentobarbital (ie, group 2) died of heart failure either during cross-clamping of the descending aorta or postoperative aortography. In conclusion, creation of a thoracic aortic dissection is possible in swine, but cross-clamping of the thoracic descending aorta and pentobarbital anesthesia should be avoided.

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