Sudden cardiac death (SCD), presumably because of ventricular tachyarrhythmias, remains one of the major challenges of contemporary cardiology. Major randomized controlled trials conducted in patients with coronary artery disease (CAD) with the aim of primary prevention of SCD are providing insights. Several large-scale studies have demonstrated that treatment with β-blockers, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and statins results not only in a reduction in all-cause mortality but specifically also in SCD. On top of this optimized pharmacological therapy, implantable cardioverter-defibrillators (ICD) further decrease the risk of overall and SCD mortality in carefully selected patient groups. The sum of these trials indicates, however, that the benefit associated with ICD therapy is most prominent in patients with chronic stable CAD. In contrast, patients early after myocardial infarction derive less benefit from ICD treatment, presumably because of a high competing risk of non-arrhythmic cardiovascular death. Optimized pharmacological therapy, together with the ICD, can substantially improve the prognosis of high-risk CAD patients. (Circ J 2005; 69: 625 - 629)

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Background Preinfarction angina improves survival after acute myocardial infarction (AMI) in nonelderly but not elderly patients in the thrombolytic era. However, it remains unclear whether preinfarction angina has a beneficial effect on clinical outcome in elderly patients undergoing percutaneous coronary intervention (PCI). Methods and Results The study group comprised 484 anterior AMI patients who were admitted within 24 h of onset and underwent emergency PCI. Patients were divided into 2 groups: those aged <70 years (nonelderly patients, n=290) and those aged ≥70 years (elderly patients, n=194). Angina within 24 h before AMI was present in 42% of nonelderly patients and in 37% of elderly patients. In nonelderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (1% vs 7%, p=0.02). Similarly, in elderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (6% vs 16%, p=0.03). Multivariate analysis showed that the absence of preinfarction angina was an independent predictor of in-hospital mortality in both nonelderly (odds ratio 4.20; 95% confidence interval (CI) 1.20-10.6; p=0.04) and elderly patients (odds ratio 3.04; 95%CI 1.06-18.1; p=0.04). Conclusions Angina within the 24 h before AMI is associated with better in-hospital outcomes in elderly and nonelderly patients. (Circ J 2005; 69: 630 - 635)

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Background Although the anti-atherosclerotic effects of HMG-CoA reductase inhibitors are well known, their specific effect on saphenous vein grafts after coronary artery bypass graft (CABG) operation is not well documented and has not been studied in Japan, so the aim of the present prospective randomized controlled study involving 27 Japanese institutions was to investigate the effects of pravastatin on the progression of atherosclerosis in such grafts and native coronary arteries after CABG. Methods and Results A total of 303 patients who had undergone CABG were randomly assigned to either the pravastatin group (n=168) or the control group (n=167). Paired coronary angiograms were obtained at baseline and at the end of 5-year follow-up in 182 (60%) patients. The low-density lipoprotein cholesterol concentration significantly decreased in the pravastatin group from 141.4 mg/dl to 113.7 mg/dl (-19.6%), compared with 141.1 mg/dl to 133.7 mg/dl (-5.2%) in the control group (p<0.001). Although there was no significant difference in the quantitative coronary angiography measurements between the 2 groups, the global change score indicated a significant pravastatin-mediated reduction in plaque progression (p<0.01). Conclusions Pravastatin can potentially reduce atherosclerotic progression in both the bypass graft and native coronary arteries of patients after CABG. (Circ J 2005; 69: 636 - 643)

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Background The plasma concentration of lipoprotein (a) [Lp(a)] is associated with atherosclerotic and thrombotic vascular diseases. The aim of the present study was to evaluate the association between plasma Lp(a) concentration and in-stent restenosis. Methods and Results One hundred and 9 patients with successful elective coronary stent implantation underwent follow-up angiography at 24±6 weeks. Restenosis after stent implantation occurred in 38 patients. Univariate analysis showed that the reference diameter of the lesion was smaller in the restenosis group (2.93±0.29 mm) than in the no-restenosis group (3.21±0.43 mm) (p<0.05). The lesion was longer in the restenosis group (14.2±5.3 mm) than in the no-restenosis group (11.6±4.9 mm) (p<0.05). Plasma Lp(a) concentrations in the restenosis group (30.5±23.9 mg/dl) were higher than in the no-restenosis group (16.9±11.1 mg/dl) (p<0.01). Other lipid concentrations were similar in both groups. Among the plasma Lp(a) concentrations, the rate of restenosis (71.4%) in the high Lp(a) group (>40 mg/dl) (n=14) was greater compared with the other groups: 33.3% in the intermediate Lp(a) group (10-40 mg/dl) (n=54), and 24.4% in the low Lp(a) group (<10 mg/dl) (n=41) (p<0.01). The late loss (0.57±0.53 mm) in the low Lp(a) group was significantly less than the other groups: 0.88±0.47 mm in the intermediate Lp(a) group, and 1.08±0.56 mm in the high Lp(a) group (p<0.05). In a multivariate regression model, plasma Lp(a) concentration remained significant as an independent predictor of restenosis in patients undergoing stent implantation (p=0.020 odds ratio (OR) 1.37 95%conficence interval (CI) 1.050-1.793), although the reference diameter (p=0.025 OR 0.23 95%CI 0.061-0.830) and lesion length (p=0.021 OR 1.12 95%CI 1.017-1.232) were related to stent restenosis. Conclusions Plasma Lp(a) concentration is an independent predictor of stent restenosis. (Circ J 2005; 69: 644 - 649)

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Background Although it has been reported that the glycoprotein IIb/IIIa inhibitor, tirofiban, is beneficial in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI), there is little data concerning the risks and complications of tirofiban therapy in Korean patients. Methods and Results The present study reviewed 261 patients who underwent tirofiban administration for ACS between May 2002 and August 2003. The rates of bleeding, transfusion, and thrombocytopenia were analyzed and the rates of complications by age, gender, and PCI vs medical treatment werecompared. The rate of minor bleeding was 8.1% (21 patients), major bleeding was 2.3% (6 patients), transfusion was 4.6% (12 patients), and thrombocytopenia was 1.2% (3 patients). Minor bleeding showed a similar rate in both sexes (8% in males vs 8.1% in females) but was higher with older age (12.5% ≥65 vs 2.6% <65 years old, p=0.093). Major bleeding occurred more in older females (5.4% vs 0%, 4.2% vs 0%, p=0.25, 0.093, respectively). The rates of thrombocytopenia and transfusion were higher in old age (2.1% vs 0% by gender, 8.3% vs 0% by age, p=0.052, 0.087 respectively). The rates of complications were similar for groups compared with PCI or medical treatment, and vascular access route. Conclusions The results suggest that tirofiban is a safe and tolerable therapy for Korean patients with ACS. (Circ J 2005; 69: 650 - 653)

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Background The aim of the present study was to investigate the relationship between plasma concentrations of endothelin (ET)-1 and clinical outcome (including mortality) and left ventricular (LV) systolic function in acute myocardial infarction (AMI). Methods and Results The study group comprised 110 consecutive first-AMI patients who were successfully reperfused by primary coronary intervention. Plasma ET-1 concentrations were evaluated 24 h from onset and the patients were divided into 2 groups according to the median value, either a high group (H group: ≥2.90 pg/ml plasma ET-1; n=55) or low group (L group: <2.90 pg/ml plasma ET-1; n=55). Major complications and LV systolic function were monitored in the 2 groups. Both highly sensitive C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP) showed a significant positive correlation with ET-1 (BNP: r=048, p<0.0001, hs-CRP: r=0.43, p<0.001). Chronic stage left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI) were significantly poorer in the H group (LVEF: 51±15% vs 60±13%, p=0.003, LVEDVI: 74±19 ml/m² vs 66±14 ml/m², p<0.05). There were significantly more major complications in the H group than in the L group (cardiogenic shock: 18% vs 5%, p=0.04; cardiac death: 13% vs 0%, p<0.01). Conclusions In the setting of AMI, plasma ET-1 concentrations may be closely related to LV systolic dysfunction and poor patient outcome, including mortality. (Circ J 2005; 69: 654 - 658)

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Background Whether or not patients with coronary artery disease (CAD) could be easily detected at the bedside using dipyridamole stress was investigated using a portable type signal-averaged electrocardiography (portable SAECG). Methods and Results The standard 12-lead QRS wave SAECG was performed at the bedside before and after dipyridamole stress in 30 patients with angiographically significant stenotic lesions, who had positive myocardial ischemia in the dipyridamole-thallium myocardial perfusion imaging (CAD group), and 33 patients with no significant stenotic lesions, who had negative imaging (control group). The filtered QRS duration (fQRSd) before and after dipyridamole stress was determined by the vector magnitude method and the difference (ΔfQRSd) was obtained. Furthermore, the ΔfQRSd was obtained using the multiphasic oscillation method, as well at the same standard 12-lead, and the maximal value of changes in fQRSd (MAX ΔfQRSd) between the 12 leads was determined. The ΔfQRSd was similar between 2 groups (p=0.11). The MAX ΔfQRSd associated was significantly greater in the CAD group (p<0.0001). When a cut-off value of MAX ΔfQRSd ≥ 5 ms was used for the detection of CAD, the sensitivity and specificity were 97 and 94%, respectively. Conclusion The portable dipyridamole-stress SAECG easily detect CAD and myocardial ischemia at the bedside. (Circ J 2005; 69: 659 - 665)

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Background T-wave morphology analysis (TMA) quantifies irregularities of ventricular repolarization based on singular value decomposition of the 12-lead electrocardiogram (ECG). Furthermore, TMA is useful for risk stratification of patients with myocardial infarction (MI), although gender differences in TMA and the relationship between TMA and heart diseases are unknown. The aim of this study was to evaluate the significance of TMA in healthy individuals and patients with heart diseases. Methods and Results Patients with heart disease and either with or without an implanted cardioverter defibrillator (ICD, n=33, 57±16 years; non-ICD, n=50, 67±10 years) were studied. Normal control ECGs (n=114) were selected from Marquette's database (NC, 33±13 years) and the TMA descriptors, including T-wave morphology dispersion (TMD) and percentage of the loop area (PL), were calculated. TMD was significantly lower in group NC males than in the group NC females (11±5.9 vs 22±16, p<0.0001). PL was significantly higher in group NC than in the ICD and non-ICD groups (0.63±0.12 vs 0.53±0.15, p<0.0001). TMD of group NC was significantly lower than that of the ICD and non-ICD groups (14±11 vs 47±27, p<0.0001). Conclusion There are gender differences in TMD. Abnormal values for TMA could reflect abnormalities of ventricular repolarization. (Circ J 2005; 69: 666 - 670)

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Background Atrial fibrillation is a progressive disease, which in the paroxysmal form (PAF) becomes more frequent and finally becomes chronic (CAF). A retrospective analysis of patients with PAF was conducted to examine the hypothesis that angiotensin-converting enzyme inhibitors (ACEI) will prevent the progression to CAF. Methods and Results On the basis of their treatment, 95 patients with PAF were divided into 2 groups: 42 patients treated with ACEI for hypertension throughout the period of treatment and follow-up (ACEI group) and 53 patients not given ACEI (non-ACEI group). Cardiac rhythms were assessed either from the medical records or the electrocardiograms recorded every 2-4 weeks at follow-up visits. The mean follow-up time was 8.3±3.5 years. There was no significant difference in the use of antiarrhythmic drugs, left atrial diameter or left ventricular ejection fraction between the 2 groups. The Kaplan-Meier curve for the time to occurrence of CAF showed a lower incidence of CAF in the ACEI group and demonstrated that the 5-year probability for persistence of PAF without progression to CAF was 88.3%, but 47.5% in the non-ACEI group. Conclusions These results indicate that ACEI will prevent progression from PAF to CAF. (Circ J 2005; 69: 671 - 676)

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Background It is important to rapidly distinguish patients with acute aortic dissection of the ascending aorta (AADa) from those with acute myocardial infarction (AMI), because minimizing the time to initiation of reperfusion therapy leads to maximum benefits for AMI and erroneous reperfusion therapy for AADa can produce harmful outcomes. The aim of this study was to find a simple test to distinguish such patients. Methods and Results Data were collected from 29 consecutive patients with AADa and 49 consecutive patients with AMI who were admitted within 4 h of the onset of symptoms. The D-dimer concentration and the ratio of the maximum upper mediastinal diameter to the maximum thoracic diameter on plain chest radiograph (M-ratio) in the emergency room were studied retrospectively. Setting the cutoff values of the D-dimer concentration and the M-ratio to 0.8 or 0.9 μg/ml and 0.309, respectively, gave a sensitivity of 93.1% and 93.1% for AADa, respectively, and a sensitivity of 91.8% and 85.7% for AMI, respectively. Conclusions The D-dimer value and the M-ratio, with appropriate cutoff values, have potential as tests that can be routinely used to exclude AADa patients from patients diagnosed with AMI prior to reperfusion therapy. (Circ J 2005; 69: 677 - 682)

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Background The magnitudes of the first (WI₁) and the second wave-intensity peak (WI₂) during the ejection period can be used as indices of left ventricular (LV) contractility and relaxation, respectively. However, use of WI to characterize LV dp/dt and the end-diastolic volume (V_ed) relationship may be more problematic, as WI may be affected by changes in preload. Methods and Results The LV pressure-volume data sets, consisting of 23 recordings obtained by the conductance method from 12 heart disease patients, were studied. End-systolic elastance (E_es) and volume-axis-intercept (V₀) were calculated with varying preload. Time constant of LV relaxation (τ), V_ed, and WI were calculated from steady-state averaged data. The E_es showed a weak correlation with WI₁ (r=0.46, p<0.05) but a better correlation with preload-adjusted WI₁ [WI₁/V _ed; r=0.86, WI₁/V_ed²; r=0.92, WI₁/(V_ed - V₀)²; r=0.89, all p<0.01]. Similarly, τ did not correlate with WI₂ but did correlate with preload-adjusted WI₂ [WI ₂/V_ed; r=-0.73, WI₂/V_ed ²; r=-0.63, WI₂/(V_ed - V₀) ²; r=-0.78, all p<0.01]. Conclusions These data demonstrate the importance of preload-adjustment when using the WI index for simultaneous assessment of LV contractility and relaxation. (Circ J 2005; 69: 683 - 687)

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Background To explore an alternative to the systemic vascular resistance index (SVRI) for monitoring peripheral circulation in patients in the intensive care unit (ICU), the resistive index (RI) in the upper extremity arteries was measured by using surface Doppler ultrasound. Methods and Results The correlation between RI and vascular resistance was assessed in vitro using a vessel phantom in a Donovan-type mock circulation system. In addition, 15 ICU patients who had undergone open-heart surgery were studied. Mean arterial pressure, central venous pressure and cardiac output were measured 30 times at 10 min intervals after patients returned to the ICU following surgery, and the SVRI was calculated from these parameters. At the same time points, 3 parts of the upper extremity arteries (brachial artery in the cubital fossa (BA), radial artery at the wrist (RA), and radial artery at the anatomical snuffbox (SB)) were scanned by Doppler ultrasound, and the resistance index (RI) for each artery region was calculated. In vitro, RI increased with higher vascular resistance, exhibiting a significant correlation (r=0.982, p<0.0001). In vivo, the average incidence angles at the BA and RA were larger than 60°, while that at the SB was only 11.5±10.8°. The overall correlation between SVRI and RI for all patients was not significant for the BA or RA, but was significant for the SB (p<0.0001). In individual patients, the correlation of SVRI with RI at the BA or RA was significant in 3 patients only, whereas significant correlation for the SB was observed in all patients. Doppler waveform analysis at the SB revealed diastolic flow reversal with increased SVRI. Conclusions Measurement at the SB provides an ideal ultrasound incidence angle for the measurement of blood flow velocity. Hence, RI measured in this way may serve as an indicator of peripheral vascular resistance, and may be effective for the evaluation of peripheral circulatory disturbance. (Circ J 2005; 69: 688 - 694)

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Background Sleep apnea syndrome (SAS) and exercise hyperpnea are common in patients with chronic heart failure (CHF), and although it is not known whether they are both regulated by the same mechanisms, the hypothesis of the present study was that they are related to augmented central chemosensitivity. Methods and Results The oxygen desaturation index (ODI) was evaluated in 29 patients and those with ODI >5 times/h underwent polysomnography. Patients with an apnea - hypopnea index (AHI) >15 /h without evidence of obstructive apnea were defined as central SAS (CSAS). Cardiopulmonary exercise testing was performed to determine peak oxygen uptake and the VE - VCO₂ slope. A hypercapnic gas mixture (7% CO₂/93% O₂) was used to activate the central chemoreflex. Nine patients had central SAS (CHF-CSAS) and 20 did not have apnea (CHF-nonSAS). Patients with CHF-CSAS had a lower peak oxygen uptake than the CHF-nonSAS group (13.0±2.4 vs 16.9±4.3 ml · kg^-1 · min^-1, p<0.05). There was a significant correlation between central chemosensitivity and the AHI (r=0.63, p<0.05), between central chemosensitivity and the VE - VCO₂ slope (r=0.50, p<0.01), whereas the VE - VCO₂ slope showed an insignificant tendency to correlate with AHI (r=0.44, p=0.07). Conclusion CHF-CSAS is associated with impaired exercise tolerance and elevated central chemosensitivity is the responsible mechanism for CSAS and exercise hyperpnea. (Circ J 2005; 69: 695 - 699)

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Background Left internal thoracic artery (LITA) grafts have superior patency to saphenous vein grafts (SVG). Because shear stress augments the release of nitric oxide throughout the LITA endothelium, shear stress and shear rate in coronary artery bypass grafts (CABG) may play an important role in the higher patency, so the aim of the present study was to evaluate and compare the rheologic parameters in CABG using LITA and SVG. Methods and Results Rheologic examinations were done in 197 patients using a vacuum-suction glass tube viscometer after CABG surgery was completed. Shear stress and shear rate were calculated from the geometry of the graft, blood flow in the graft and blood viscosity. Of 197 patients, 177 underwent LITA grafting to the left anterior descending artery (LAD) and 160 had SVG anastomosis to coronary arteries. Mean wall shear stress in the LITA grafts to the LAD (13.8±1.0 dyne/cm²) was nearly 4-6-fold larger than that in the SVG grafts. Mean shear rate (559.1±57.0 s^-1) of LITA-LAD grafts was approximately 2-3-fold higher than that of SVG. Conclusion These results suggest that high wall shear stress and shear rate play an important role in the higher patency rate of LITA grafts. (Circ J 2005; 69: 700 - 706)

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Background Essential hyperhidrosis, a disorder of the eccrine sweat glands, is associated with sympathetic overactivity and the aim of the present study was to determine endothelium-dependent vasodilator function in patients with this condition. Methods and Results Using high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, %FMD endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (%NTG endothelium-independent vasodilatation) was measured in 18 subjects (mean age 27±5 years) with essential hyperhidrosis and 24 healthy control subjects (mean age 29±5 years). Baseline brachial artery diameter and FMD were comparable in both groups (BAD: 4.1±0.7 mm vs 4.3±0.5 mm (control), p=0.8; FMD: 5.6±1.9% vs 6.7±2.2%, p=0.1). The time-averaged flow velocity during peak reactive hyperemia was similar in the 2 groups (75±11 cm/s vs 72±10 cm/s, p=0.5), nor did NTG-induced dilatation in the patients with essential hyperhidrosis differ significantly from that in healthy control subjects (12.8±2.7% vs 14.0±3.6%, p=0.3). Conclusion These findings suggest that endothelium-dependent dilatation of large conduit arteries is preserved in essential hyperhidrosis and it seems to be a localized disorder of the eccrine sweat glands rather than a generalized disorder involving vascular endothelium. (Circ J 2005; 69: 707 - 710)

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Background Previous ³¹P magnetic resonance spectroscopy (MRS) studies demonstrated that the myocardial phosphocreatine-to-ATP ratio offered important information concerning the degree of dysfunction and prognosis in patients with cardiomyopathy. In the present study, we investigated total creatine (CR) levels in various diseased hearts using ¹H MRS. Methods and Results Fourteeen patients with the following conditions were examined: cardiac amyloidosis (n=2); hypertensive heart disease (4); valvular disease (2); hypertrophic cardiomyopathy (2); dilated cardiomyopathy (2); restrictive cardiomyopathy (1); and post-operative atrial septal defect (1). Myocardial CR was measured using ¹H MRS with point-resolved spectroscopy localization. Overall, myocardial CR levels in diseased hearts were significantly lower than those in the control group [16.5±6.0 (n=14) vs 27.1±3.2 μmol/g (n=10), p<0.001]. There was a positive correlation between myocardial CR and left ventricular ejection fraction (42.9±13.8%, range 19.5-69.1%) despite the different mechanisms of cardiac dysfunction (r=0.60, p<0.05). Myocardial CR levels in patients who were hospitalized due to heart failure within 1 year were significantly lower than those in other patients [11.3±1.0 (n=4) vs 18.6±5.9 μmol/g (n=10), p<0.05]. Conclusions Noninvasive measurement of myocardial CR using ¹H MRS may be valuable in the assessment of disease severity and prediction of clinical course in various forms of heart disease. (Circ J 2005; 69: 711 - 716)

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Background In some stroke patients blood pressure (BP) fluctuates extensively during medical rehabilitation, so the present study investigated the influence of autonomic nervous dysfunction on the change in BP during exercise. Methods and Results The subjects consisted of 55 stroke inpatients (males, 29; mean age, 58.8 years old; ischemic/hemorrhagic etiology, 30/25) who were admitted to the Stroke Center within 2 weeks of their first stroke. The control group consisted of 15 age-matched healthy volunteers. The 24-h heart rate (HR) variability (HRV) and BP variability (BPV) were examined, and then the increase and recovery of BP and HR were measured during bicycle ergometer exercise at 4 METs. Components of 24-h HRV (low-frequency power (LF), high-frequency power (HF), LF/HF, and asleep - awake ratio of LF/HF (LF/HF_d-n)) were lower (p<0.01) and BPV was greater in the stroke group (p<0.05) than in the control group. There was a negative correlation between BP change during exercise and LF/HF or LF/HF_d-n (r=-0.43 or r=-0.58, p<0.01), and a greater increase in systolic BP (102 ±9.8 mmHg, n=7) during exercise was observed in stroke patients with lower LF/HF_d-n (≤1.0). Conclusions Lower HRV in stroke patients may relate to an increase in BP during exercise. HRV is useful for estimating the risk during medical rehabilitation. (Circ J 2005; 69: 717 - 721)

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Background Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. Methods and Results Normal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39°C followed by 20 min at 30°C. This procedure raised the rectal temperatures by about 1°C. Arterial endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein expressions were examined, and serum concentrations of nitrate were measured. The expression of eNOS mRNA in the aortas of normal controls did not change, whereas those of the TO-2 hamsters decreased with age. Four weeks of sauna therapy significantly increased eNOS mRNA expression in the aortas of TO-2 hamsters compared with those that did not undergo sauna therapy. Sauna therapy also upregulated aortic eNOS protein expression. Serum nitrate concentrations of the TO-2 hamsters were increased by 4 weeks of sauna therapy compared with those that did not undergo sauna. Conclusion Repeated sauna therapy increases eNOS expression and NO production in cardiomyopathic hamsters with heart failure. (Circ J 2005; 69: 722 - 729)

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Background Dysfunction of endothelial cells (EC) to produce endothelial nitric oxide synthase (eNOS) by tumor necrosis factor-α (TNF-α) causes critical features of vascular inflammation associated with several disease states (eg, atherosclerosis including increased platelet aggregation and adhesion on EC, elevated adhesion molecules and enhanced inflammatory cells binding to EC). 17-β estradiol (E₂) can stimulate eNOS production and improve the critical features of atherosclerosis. Using TNF-α and E₂, we attempted to develop an in vitro vascular model for studying atherosclerosis. Methods and Results Human umbilical vein endothelial cells (HUVEC) grown in transwells were cocultured with smooth muscle cells in a 24-well plate to mimic the major components of the vascular wall. The model was incubated with TNF-α (10 ng/ml) for 12 h, prior exposed to E₂ (100 pg/ml) for 6-12 h, then investigated by transmission and scanning electron microscopes. The result indicated recovered morphology with good tight junction, and decreased platelet adhesion was noted in defective HUVEC after E₂ treatment. Conclusion 17-β estradiol was represented as an antiatherosclerogenic agent to demonstrate feasibility of the model. Although our finding focused only on the endothelium, this would be the basis for our future studies to develop ex vivo continuous perfusion of human vessel segments for a further atherosclerosis study. (Circ J 2005; 69: 730 - 738)

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Background Nifekalant, a class III anti-arrhythmic agent, has been used clinically at serum concentrations of 1-10 μmol/L in patients with ventricular arrhythmias. However, the effect of nifekalant on triggered arrhythmias has not yet been established. Methods and Results Trabeculae were dissected from the right ventricles of 16 rat hearts. The force was measured using a silicon strain gauge, the membrane potential using ultra-compliant microelectrodes, and the regional intracellular Ca²⁺ ([Ca²⁺]_i) using electrophoretically microinjected fura-2 and an image intensified CCD camera at a sarcomere length of 2.1 μm. Rapid cooling contractures (RCCs) were measured to estimate the Ca²⁺ content in the sarcoplasmic reticulum. Ca²⁺ waves and aftercontractions were measured after the induction of reproducible Ca²⁺ waves. Nifekalant at 1, 10 and 250 μmol/L increased significantly the action potential duration, the peak [Ca²⁺]_i, the developed force and the amplitude of RCCs in a concentration-dependent manner (stimulus interval =2 s, [Ca²⁺]_o =0.7 mmol/L, 26.0±0.2°C). Nifekalant at 10 and 250 μmol/L increased significantly the velocity of Ca²⁺ waves with an enhancement of the aftercontractions (stimulus interval =0.5 s for 7.5 s, [Ca²⁺] _o =1.8±0.1 mmol/L, 22.3±0.5 °C). Conclusions Nifekalant, even at a therapeutic concentration, can increase muscle contraction, but may worsen triggered arrhythmias because of the acceleration of Ca²⁺ waves under Ca²⁺-overloaded conditions. (Circ J 2005; 69: 739 - 745)

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A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas. She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-β-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions. (Circ J 2005; 69: 746 - 751)

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A 53-year-old woman with Takayasu arteritis was admitted to hospital because of worsening exertional angina. Coronary angiography revealed 90% ostial stenosis in the left main coronary artery (LMCA), which also involved the bifurcation of the relatively short LMCA. Because the patient refused coronary bypass surgery, she underwent percutaneous coronary intervention (PCI) and the stenosis was successfully dilated. However, the exertional angina recurred a few months later and again after the second PCI. Finally, a sirolimus-eluting stent was deployed in the in-stent restenotic lesion. The patient has been free from angina pectoris for 6 months after the last PCI and follow-up coronary angiography indicated no restenosis in the LMCA. (Circ J 2005; 69: 752 - 755)

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A patient presented with paroxysmal atrial fibrillation (AF) caused by focal rapid discharges arising from the ostium of the inferior vena cava (IVC). Surface ECG showed typical features of AF and flutter when rapid activation at the IVC ostium was conducted to the right atrium in a 1-to-1 and 2-to-1 fashion, respectively. Discrete radiofrequency energy applications at the medial ostium of the IVC completely eliminated the atrial tachyarrhythmias. (Circ J 2005; 69: 756 - 759)

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A 66-year old man, who had been diagnosed with dilated cardiomyopathy and felt a progressive shortness of breath and fatigability, was admitted to hospital. Computed tomography showed a thickening of the aortic wall from the aortic arch to the aortic bifurcation, as well as mild pleural and pericardial effusion. Intravenous pyelography showed severe ureteral stenosis, along with hydronephrosis, of the left side. There was a marked increase in C-reactive protein and the erythrocyte sedimentation rate, but the serology for connective tissue disease and perinuclear antineutrophil cytoplasmic antibodies was negative. Retroperitoneal fibrosis (RPF) with intrathoracic extension was diagnosed. After confirming the absence of malignant disease, an oral predonisolone treatment of 30 mg/day was started, and this ameliorated the ureteral obstruction, aortic wall thickening and pericardial effusion. The patient had been taking 300 mg of loxoprofen sodium for headaches every day for 16 years. The relationship between loxoprofen, cardiomyopathy and RPF remains unclear. There is a possibility of RPF in the patients with a thickening of thoracic aortic wall, as in this case. (Circ J 2005; 69: 760 - 762)

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Background Myelosuppressives such as cyclophosphamide (Cy) and 5-fluorouracil (5FU), which can increase circulating CD34⁺ cells, may have a beneficial effect in the post-infarct heart. Methods and Results Twenty-four hours after 30-min ischemia - reperfusion, rabbits were intravenously treated with Cy (20 mg/kg), 5FU (15 mg/kg) or saline (S). Cy significantly improved cardiac function and remodeling and decreased the old infarct area 1 month after infarction, compared with those given S. The number of circulating CD34⁺ cells was higher and neovascularization and matrix metalloproteinase-1 was induced in the Cy group. Conclusion Cy has potential for post-infarct treatment. (Circ J 2005; 69: 763 - 765)

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