Background Recent large-scale genome-wide association studies have identified several loci associated with the risk of coronary artery disease (CAD). The aim of the present study was to examine whether the previously reported CAD-associated single-nucleotide polymorphisms (SNPs) confer susceptibility to myocardial infarction (MI) in a study population of 2,475 controls and 589 cases of MI. The effect of the CAD-associated SNPs on cardiovascular risk factors in the control group was also investigated. Methods and Results Significant associations were observed between 2 SNPs, rs1333049 on chromosome 9p21 and rs17465637 on chromosome 1q41, and MI, with odds ratios adjusted for age, sex, diabetes, hypertension and smoking habit of 1.47 (95% confidence interval (CI), 1.15-1.89; corrected p=0.006) and 1.45 (95%CI, 1.15-1.83; corrected p=0.006) for rs1333049 and rs17465637, respectively. None of the genotypes was associated with body mass index, plasma lipid profile, blood pressure, glucose, or hemoglobin A_1c. The genotypes also had no effect on the marker of inflammation (C-reactive protein) or atherosclerosis (mean and maximum carotid intima - media thickness). Conclusions Although the underlying mechanisms are not clearly understood, the previously reported association between the 2 SNPs (rs1333049 and rs17465637) and MI was reproduced in this Japanese sample. (Circ J 2008; 72: 1213 -1217)

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Background Because many Japanese patients with hypercholesterolemia have received statin therapy for nearly a decade, there was a need to investigate the benefit of long-term treatment. The Japan Lipid Intervention Trial (J-LIT) Extension 10 study was planned to continue the original J-LIT study for a total of 10 years. Methods and Results All 51,321 patients (including 19,905 who agreed to continue the study) were analyzed. Low-dose treatment with simvastatin (mainly 5 mg/day) was continued throughout the study period and serum lipid levels were well controlled over 10 years. Incidence of adverse drug reactions during the 4-year extension period was lower than previously. Serum total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels showed a positive correlation with the risk of coronary events, whereas high-density lipoprotein-cholesterol showed an inverse correlation. Patients with an LDL-C level ≥140 mg/dl had a far higher risk of coronary events than those with a level <100 mg/dl. Conclusions Long-term, low-dose simvastatin therapy was safe and effective in Japanese patients with hypercholesterolemia. Serum LDL-C levels should be <140 mg/dl to decrease coronary risk and a low cholesterol level should be maintained for as long as possible. (Circ J 2008; 72: 1218 - 1224)

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Background Recurrent acute myocardial infarction (AMI) is a deteriorated condition with high in-hospital morbidity and mortality, but the predictors of in-hospital outcome after primary percutaneous coronary intervention (PCI) for repeat AMI remain unclear. Methods and Results Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings, results of primary PCI, and in-hospital prognosis were retrospectively compared between primary PCI-treated AMI patients with previous myocardial infarction (MI) (repeat-MI patients, n=235) and those without previous MI (first-MI patients, n=1,550). The repeat-MI patients had higher prevalence of Killip class ≥3 at admission, larger number of diseased vessels, and a significantly higher in-hospital mortality rate than the first-MI patients. On multivariate analysis, number of diseased vessels ≥2 or diseased left main trunk (LMT) on initial coronary angiography was the independent positive predictor of in-hospital mortality in the repeat-MI patients, not in the first-MI patients, whereas acquisition of Thrombolysis In Myocardial Infarction 3 flow in the infarct-related artery immediately after primary PCI and elapsed time <24 h were the negative predictors in the first-MI patients, not in the repeat-MI patients. Conclusions Number of diseased vessels ≥2 or diseased LMT on initial coronary angiography is an independent risk factor of in-hospital death in recurrent-AMI patients undergoing primary PCI. (Circ J 2008; 72: 1225 - 1229)

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Background Limited data are available regarding the effects of phase III cardiac rehabilitation on the physical status and risk factors in elderly patients with coronary artery disease (CAD). Methods and Results Thirty-four male CAD patients (>65 years old) were randomly assigned to an intervention group (n=18) or a control group (n=16). The intervention group participated in a phase III cardiac rehabilitation program consisting of exercise training, diet therapy, and weekly counseling for 6 months. In the control group, usual outpatient care was provided. In the intervention group, body mass index, waist size and fat weight significantly decreased; peak VO₂ and anaerobic threshold VO₂ were maintained; isokinetic peak torques of knee extensor and flexor muscles significantly increased; anterior trunk flexibility was significantly improved. In the control group, all parameters were unchanged except for peak VO₂, which significantly decreased. In the intervention group, serum total cholesterol levels significantly decreased after cardiac rehabilitation. However, high-density lipoprotein-cholesterol and apoA-I levels also decreased. In the control group, no significant change in lipid profile was observed. Conclusions The results suggest that phase III cardiac rehabilitation could be beneficial for elderly patients with CAD. (Circ J 2008; 72: 1230 - 1234)

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Background The difference in the culprit plaque composition of acute coronary syndrome (ACS) patients with and without the no-reflow phenomenon has not been fully evaluated. Methods and Results Intravascular ultrasound radiofrequency data of culprit plaques were obtained and analyzed in 49 ACS patients. The no-reflow phenomenon was defined as a decrease of at least 1 grade in `Thrombolysis In Myocardial Infarction' flow immediately after mechanical dilatation compared with before mechanical dilatation, with no evidence of thrombus, spasm, or dissection. The no-reflow phenomenon was observed in 9 individuals. Culprit plaques with the no-reflow phenomenon contained a higher percentage of necrotic core component and a smaller percentage of fibrous component than plaques in the patients without the no-reflow phenomenon (necrotic core component, 22.1±9.3% vs 11.7±7.9%, p=0.0011; fibrous component, 59.6±11.2% vs 68.3±10.2%, p=0.027). Multivariate analysis identified the percentage of necrotic core component as an independent predictor of the no-reflow phenomenon after adjustment for plaque geometry and procedural factors (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.5; p=0.015). Conclusion Culprit plaques of patients with the no-reflow phenomenon differ from those in patients without the no-reflow phenomenon. (Circ J 2008; 72: 1235 - 1241)

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Background Coronary artery fistula (CAF) is an anomaly resulting in the steal phenomenon of coronary blood flow, which may cause morbidity or mortality. CAFs in Chinese patients after long-term follow-up of 15 years were retrospectively analyzed. Methods and Results From September, 1992 to August, 2007, 152 CAFs were detected in 28,210 coronary angiograms from 125 patients. Clinical and angiographic data of all patients were analyzed retrospectively. Two types of CAFs were characterized: type I in 99 patients with 124 solitary coronary to cardiac chamber or great vessel fistula; type II: 26 patients with 28 coronary artery - left ventricular multiple microfistulas. Single-, double-, and triple-CAFs were detected in 79%, 20%, and 1% of patients, respectively. Coexistent coronary lesions were noted in 41% of patients. Fistula-related symptoms included stable angina in 55, myocardial infarction in 2, heart failure in 2, sudden death with ventricular fibrillation in 1, and syncope in 1. Twenty-four patients had coexistent congenital anomalies. Only 9 patients underwent coronary intervention or/and surgery for CAFs. Conclusions CAFs may cause trivial or lethal cardiac events, and may coexist with coronary lesion or congenital anomaly. Coronary to cardiac chamber or great vessel fistula and coronary-left ventricular multiple microfistulas have different morphologic and pathological phenomena. (Circ J 2008; 72: 1242 -1248)

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Background Resistin, a novel adipocytokine, has been suggested as representing a link between metabolic signals, inflammation and atherosclerosis. The aim of the present study was to investigate the alteration in level of plasma resistin in patients with acute coronary syndrome (ACS) to uncover the role of resistin. Methods and Results The 39 patients with ACS and 26 age-matched healthy subjects in this cross-sectional study were investigated. Plasma resistin levels were measured using radioimmunoassay. Plasma resistin levels were significantly increased in patients with ACS at 24 h after symptoms onset and remained at a high level for 1 week, and were significantly higher in patients with acute myocardial infarction than in those with unstable angina. In addition, plasma resistin level was correlated positively with peak plasma creatine kinase (CK), the MB isoform of CK and troponin I, and was correlated negatively with left ventricular ejection fraction. No correlation was found beween plasma resistin level with level of metabolic parameters or inflammatory markers. Conclusions Plasma resistin levels in patients with ACS are elevated significantly within the first week after symptoms onset. Increased resistin levels may be a marker of myocardial ischemia and injury in ACS. (Circ J 2008; 72: 1249 - 1253)

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Background Isolated single coronary artery (SCA) is an extremely rare congenital coronary anomaly. Some subgroups of SCA can lead to angina pectoris, acute myocardial infarction or even sudden death in the absence of atherosclerosis. Young patients, especially, have the risk of serious clinical events, but middle-aged-to elderly patients have a variable clinical course. Methods and Results The aim of this study was to present the clinical and angiographic properties, relatively long-term follow-up (54±14 months) and management of adult patients (mean age 57±12 years) with SCA. The records of 70,850 patients undergoing coronary angiography between 1999 and 2005 were reviewed. Ten patients (0.024%) were found to have SCA, originating from the left sinus of Valsalva in 3 (30%) patients and from the right sinus of Valsalva in 7 patients (70%). No atherosclerotic involvement was seen in 7 (70%) patients. One patient was also treated by stent implantation to the SCA. Other patients were followed medically. All patients have been followed uneventfully. Conclusion Medical treatment is usually adequate for middle-aged to elderly patients with SCA in the absence of ischemia and/or acute coronary syndrome. (Circ J 2008; 72: 1254 - 1258)

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Background Diabetes mellitus (DM) is associated with the impairment of cerebral oxygenation during cardiac surgery. The aim of the present study was to investigate the effects of DM on cerebral oxygenation assessed by jugular bulb oxygen saturation (SjvO₂) in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB) in a prospective controlled trial. Methods and Results Twenty-three diabetic patients with glycosylated hemoglobin above 7.0% (DM group) and 23 non-diabetic patients (control group) undergoing OPCAB with no-touch aortic technique were included. A fiberoptic oximetry catheter was inserted into the jugular bulb. The lowest SjvO₂ and the number of patients with cerebral desaturation, defined as SjvO₂ less than 50% over 5 min, were recorded during coronary grafting. Three neurocognitive tests were done before surgery and at postoperative day 2 and 7. There were no differences in SjvO₂ between the groups. Furthermore, the number of patients with cerebral desaturation and all neurocognitive test scores were similar between the 2 groups. None of the patients developed neurocognitive dysfunction. Conclusions Cerebral oxygenation in diabetic patients was similar to that of non-diabetic patients and well maintained above the critical level without resulting in clinically significant postoperative neurocognitive dysfunction during OPCAB with no-touch aortic technique. (Circ J 2008; 72: 1259 - 1264)

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Background The Doppler-derived energy loss coefficient (ELCo), which can take into account the pressure recovery phenomenon and reconcile discrepancies between the aortic valve effective orifice area (EOA) obtained by the Gorlin formula using a catheter (EOA_cath) and the EOA obtained by the Doppler continuity equation (EOA_Dop), is proposed as an equivalent index to represent EOA_cath. Therefore, the purpose of this study was to evaluate the clinical impact of ELCo in patients with severe aortic stenosis (AS). Methods and Results Thirty-three patients with severe AS were assessed by Doppler examination [EOA obtained by the continuity equation (EOA_Dop) ≤1.0 cm²], and referred to the cardiac catheterization laboratory for evaluation of EOA obtained by the Gorlin formula (EOA_cath). Patients with ELCo ≤1.0 cm² (n=26) had significantly lower incidence of symptoms related to AS compared with those having ELCo >1.0 cm² (n=7) (p=0.002). Superior concordance in severity of AS was demonstrated between EOA_cath and ELCo compared with EOA_cath and EOA_Dop (κ=0.52, and κ=0.32, respectively). Conclusions In 21% of patients with "severe" AS diagnosed by Doppler echocardiography, the ELCo value indicated moderate rather than severe AS. These patients had significantly lower incidence of symptoms compared with patients who had ELCo ≤1.0 cm². (Circ J 2008; 72: 1265 - 1269)

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Background The aim of this study was to assess the age-related differences in intravascular ultrasound (IVUS) findings of target lesions in patients with coronary artery disease. Methods and Results The 1,009 patients who underwent IVUS imaging were grouped according to an increase of 10 years of age: Group I [<50 years (n=144)]; Group II [51-60 years (n=259)]; Group III [61-70 years (n=249)]; Group IV [71-80 years (n=264)]; and Group V [>80 years, (n=93)]. Calcified plaque (18%, 25%, 33%, 38%, and 46%, p<0.001) and negative remodeling (29%, 48%, 44%, 44%, and 66%, p<0.001) were most common, and reference segment plaque burden (35±11%, 35±10%, 39±10%, 38±10%, and 40±11%, p<0.001) was greatest in Group V. Plaque rupture (52%, 31%, 42%, 38%, and 20%, p=0.009) and thrombus (38%, 30%, 31%, 24%, and 11%, p=0.026) were most common in Group I. In the multiple logistic regression analysis, patient age was an independent predictor of calcified plaque (odds ratio (OR)=1.03, p=0.001), negative remodeling (OR=1.04, p=0.001), and mean reference segment plaque burden >50% (OR=1.03, p=0.006). Conclusion Elderly patients have more severe calcifications with negative remodeling and diffuse atherosclerosis, whereas younger patients have more unstable plaque morphology. (Circ J 2008; 72: 1270 - 1275)

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Background Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). Multidetector computed tomography (MDCT) allows the non-invasive assessment of coronary artery stenosis and plaque properties. In this study, we investigated whether 64-slice MDCT could non-invasively detect a plaque rupture in patients with de novo angina. Methods and Results The study population comprised 67 patients with de novo angina. All patients underwent contrast-enhanced 64-slice MDCT and intravascular ultrasound (IVUS). Patients were divided into a plaque rupture group (n=27) and a non-rupture group (n=40) based on the IVUS. The 64-slice MDCT revealed that the prevalence of an ulcer-like enhancement space (37% vs 5%, p<0.01), a ring-like sign (41% vs 18%, p=0.04), in the plaque rupture group was higher than those in the non-rupture group. Maximum plaque thickness (2.1±0.9 mm vs 1.6±1.0 mm, p=0.04), outer vessel area (17.6±4.9 mm² vs 13.4±5.0 mm², p<0.01), percentage plaque area (82.3±9.1% vs 73.4±15.7%, p=0.01), and remodeling index (1.11±0.18 vs 1.01±0.15, p=0.04) of the plaque rupture group were all significantly larger than those of the non-rupture group. Conclusions The 64-slice MDCT can identify differences in lesion morphologies between ruptured plaques and non-ruptured plaques. From our results, the 64-slice MDCT might provide a useful tool for the non-invasive detection of plaque rupture. (Circ J 2008; 72: 1276 - 1281)

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Background The loading dose of ticlopidine is 500 mg in both the US and Europe and 200 mg in Japan. A lower loading dose of clopidogrel might achieve adequate platelet inhibition in Japanese patients. Methods and Results Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 150-mg (n=20) and 300-mg (n=20) clopidogrel loading. Platelets were stimulated with 5 and 20 μmol/L adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Pretreatment ADP-induced platelet aggregation in the 150-mg clopidogrel group did not differ from that of the 300-mg group. The administration of 300-mg clopidogrel loading dose resulted in lower platelet aggregation 2 h after the administration (5 μmol/L ADP: 53±9% vs 61±12%, p<0.05 and 20 μmol/L ADP: 61±10% vs 68±9%, p<0.05). A lower platelet aggregation induced with 20 μmol/L ADP was still observed 4 h after the 300-mg clopidogrel loading (58±10% vs 65±9%, p<0.05). Conclusions The 150-mg clopidogrel loading does not achieve rapid platelet inhibition. The 300-mg loading dose should be used to suppress platelet function rapidly even in Japanese patients undergoing coronary stent placement. (Circ J 2008; 72: 1282 - 1284)

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Background Although the common trunk of left pulmonary veins (PVs) has been reported as a relatively popular anatomical variation of PVs, little is known about the coalescence of contralateral PVs. The present study was conducted to reveal the prevalence and electrophysiologic characteristics of the confluent inferior common PVs. Methods and Results Anatomical variation in the PV drainage to the left atrium (LA) was assessed using the multidetector computed tomography scan in 326 patients with atrial fibrillation (AF) who underwent the PV isolation procedure. Coalescence of inferior PVs was observed in 5 cases (1.5%). Both inferior PVs conjoined prior to the junction with the LA in 3 cases, while they coalesced at the LA junction in the other 2 cases. The arrhythmogenic activities of the confluent inferior PVs were generally low in all cases without any ectopic firings triggering the observed AF. All inferior PVs, as well as the superior PVs, were successfully isolated either en bloc at the common trunk or individually at the orifice of each PV. Conclusions Confluent inferior PVs were present in 1.5% of cases in patients with AF who underwent the PV isolation procedure. Preoperative recognition of this venous anomaly by 3-dimensional imaging is important for smooth and safe ablation. (Circ J 2008; 72: 1285 - 1290)

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Background After the arterial switch procedure, decreased distensibility of the aortic root has been reported, which means impaired aortic reservoir function of the coronary circulation, but there have been no reports regarding the relationship of this issue to myocardial perfusion. Therefore, in the present study the aortic reservoir function and coronary supply-demand balance were examined in patients after undergoing the arterial switch operation (ASO) around the time of entering elementary school. Methods and Results Diastolic runoff (DR), which is the percentage of diastolic blood flow to total cardiac output, was measured as the index of aortic reservoir function. The subendocardial viability ratio was investigated as the index of coronary supply - demand balance. In the patient group, the aortic root was dilated (p<0.0001) and distensibility was impaired (p<0.0001) in comparison with an age-matched control group. However, there was no difference between the 2 groups in DR or subendocardial viability ratio. Conclusions Coronary supply - demand balance was preserved in the pediatric ASO patients, despite the aortic root dysfunction. The preserved DR suggests that dilatation of the aorta compensates for aortic reservoir function. Because large artery dysfunction predicts future cardiovascular diseases, careful follow-up is crucial. (Circ J 2008; 72: 1291 - 1295)

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This article was retracted. See the Notification.

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Background Various cytokines are involved in the pathogenesis of sarcoidosis, but their expression in the myocardium has not been documented for cardiac sarcoidosis. Methods and Results Myocardial tissue was obtained from 12 patients with cardiac sarcoidosis at the time of left ventriculoplasty, biopsy or autopsy. mRNA expression of various inflammatory cytokines was analyzed using quantitative real-time polymerase chain reaction, as well as by immunohistochemistry. Ten patients with dilated cardiomyopathy (DCM) served as controls. Enhanced expression of interleukin (IL)-1α, IL-2, IL-12 p40 and interferon (IFN)-γ mRNA was limited to the myocardium of cardiac sarcoidosis patients. Expression of IL-1β, IL-8, IL-10, IL-15 and TNF-αoccurred in both cardiac sarcoidosis and DCM patients, but IL-4 and IL-5 were not detected in either disease. Immunohistochemistry of the myocardial tissue of sarcoidosis revealed positive staining for IL-12 and IFN-γ. IL-12 was localized in multinucleated giant cells and macrophages of the sarcoid granulomas, whereas IFN-γwas detected in lymphocytes and vascular endothelial cells. Conclusions Type 1 helper T-cell cytokines may be involved in the pathogenesis of cardiac sarcoidosis. (Circ J 2008; 72: 1303 -1307)

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Background In clinical practice, using the patient's waist circumference (WC) to evaluate visceral obesity may underestimate disorders with a metabolic origin. This study examined whether or not the WC derived from the cut-off point of the visceral fat area (VFA) can reflect the features of metabolic syndrome (MetS) in premenopausal women. Methods and Results Computed tomography-scanned VFA, MetS components and the concentrations of high-sensitivity C-reactive protein (CRP) and adiponectin were measured in a total of 349 premenopausal women. The VFA at the L1 and the L4 sites was a significant index (p<0.001) of incremental MetS risk. Receiver-operating characteristic curve analysis showed that 75 cm² of VFA at L4 and 87.5 cm² at L1 were the optimal thresholds for discrimination of MetS risk. Significant differences in all MetS components, as well as CRP (p<0.05) and adiponectin levels (p<0.005), were observed when subjects were subdivided by the L4 VFA cut-off point (<75/≥75 cm²), whereas there was a significant difference only in the triglycerides level in the groups divided by WC (WC <88/≥88 cm). Moreover, subjects with a lower WC - higher VFA showed a similar pattern in MetS components and lower adiponectin than those with a higher WC - higher VFA. Conclusions This study clarified that VFA rather than WC is a major determinant of MetS risk in premenopausal women. (Circ J 2008; 72: 1308 - 1315)

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Background This study was designed to evaluate the joint effects of plasma C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) vs coronary angiographic severity on cardiovascular risk stratification. Methods and Results A total of 345 patients with stable coronary artery disease (CAD) were recruited after successful percutaneous coronary intervention (PCI). Endpoints were major adverse cardiovascular events (MACE) and cumulative clinical restenosis rate after 18-36-month follow-up. Plasma NT-proBNP and CRP levels were among the strongest predictors of MACE. Adjusted hazard ratios of MACE according to combined biomarkers were 2.4 (p=0.05) for elevated CRP only, 5.22 (p<0.001) for elevated NT-proBNP only, and 7.04 (p<0.001) for elevation of both. The differential capacity using both plasma CRP and NT-proBNP in a receiver-operating-characteristics curve analysis (area under curve, AUC: 0.82) was significantly higher than using either biomarker alone or conventional risk factors (AUC: 0.67). Significant predictors of clinical restenosis were plasma NT-proBNP and the Gensini score. The combination of NT-proBNP and the Gensini score was the strongest predictor (AUC: 0.77) for clinical restenosis. Conclusions Plasma NT-proBNP, CRP, and the Gensini score are complementary in risk stratification. Combined use of these biomarkers has provided substantial extra information to conventional risk factors in stable CAD patients. (Circ J 2008; 72: 1316 - 1323)

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Background The relationship between C-reactive protein (CRP) concentration and hypertension and interactions between CRP and other risk factors on hypertension have not been studied in Mongolian people of Inner Mongolia, China. Methods and Results A total of 767 hypertensives and 762 non-hypertensives people aged 30 or more were selected as participants for the case-control study. Lifestyle risk factors and family history of hypertension were investigated, body weight measured, fasting plasma glucose, blood lipids, insulin and CRP examined for all participants. After adjustment for covariates, high level of CRP (≥2.54) were associated with hypertension and the odds ratio (OR) was 1.337. The participants were also divided into even quartiles of CRP, compared to the lowest quartile, multivariate adjusted OR were 1.144, 1.330, 1.556 for the second, third and fourth quartiles of CRP, respectively. There were significant interactions between increased CRP and cigarette smoking, and insulin resistance on hypertension, corresponding relative excess risk due to interactions were 0.799 and 0.651, respectively. Conclusion Increased CRP was associated with hypertension, there were interactions between increased CRP and cigarette smoking, and insulin resistance on hypertension in Mongolian people. (Circ J 2008; 72: 1324 - 1328)

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Background The aim of the present study was to measure peripheral blood flow (BF) with a new finger-occlusion plethysmograph (FOP) and to compare this to BF measured with a laser Doppler flowmeter (LDF). An additional objective was to investigate the relationship between hypertension-related clinical parameters and peripheral vascular resistance (PVR) estimated from BF and mean blood pressure (BP) (PVR = mean BP/BF) in young subjects. Methods and Results The present study employed 101 young volunteers (61 males, 40 females, mean age 23.2±2.5 years). The FOP was attached to the third finger and an LDF to the fourth fingertip of each subject. BF was measured simultaneously by the 2 devices. A multi-biomedical recorder (TM2425) measured 24-h BP. A high correlation was observed between BF measured by the FOP and LDF (r=0.79, p<0.001). In multiple linear regression analysis, PVR was independently correlated with a family history of hypertension (p<0.01) and with base diastolic BP during sleep (p<0.01), which is a sensitive predictor of severity of hypertension. Conclusions Our newly developed FOP can estimate peripheral absolute BF easily. Furthermore, BF determined by the FOP can be used to calculate PVR, and an elevated PVR may be a useful predictor of hypertension. (Circ J 2008; 72: 1329 - 1335)

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Background We examined the effects of bone marrow-derived mononuclear cells (BMDMNCs) on preventing viable myocardium damage from myocardial infarction (MI) in a rat MI model. Methods and Results Saline (group 1) or BMDMNCs (group 2) were implanted into the infarct area (IA) of 1-week-old anterior wall MI Sprague - Dawley (SD) rats. Twenty SD rats without MI served as the controls (group 3). The results demonstrated that in remote viable myocardium, the integrated area (μm²) of connexin43 spots was lower, whereas the number of apoptotic nuclei were higher in group 1 than in groups 2 and 3 on day 90 following BMDMNC implantation (all p<0.001). Additionally, the number of vessels and survival myocardium in the IA was lower in group 1 than in groups 2 and 3 (all p<0.005). Furthermore, the mRNA expressions of nitric oxide synthase, interleukin-8/Gro-α, interleukin-10 and matrix metalloproteinase-9 were higher in group 2 than in groups 1 and 3 in peri-IA (all p<0.05). On days 42 and 90, the left ventricular (LV) function was lower in group 1 than in groups 2 and 3 (p<0.001). Conclusions Autologous BMDMNC therapy improves LV function, and mitigates molecular and cellular perturbation following MI. (Circ J 2008; 72: 1336 - 1345)

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Background A previous report showed that aldosterone upregulates angiotensin converting enzyme (ACE) gene expression levels in cultured neonatal rat cardiocytes. ACE2 is a novel homologue of ACE, which exists in the human heart, and ACE2 converts angiotensin I to angiotensin 1-9 and angiotensin II to angiotensin 1-7, thereby decreasing angiotensin II levels. In the present study, an investigation took place to see whether aldosterone regulates the expression of ACE2 as well as that of ACE in cultured neonatal rat cardiomyocytes. Methods and Results Primary neonatal rat cardiomyocytes were cultured with aldosterone. Total RNA was extracted from these cardiomyocytes and quantified the mRNA levels of ACE2, ACE and GAPDH by using real-time reverse transcription polymerase chain reaction analysis. Aldosterone significantly decreased ACE2 mRNA levels and increased ACE mRNA levels at 12 h. Angiotensin II, however, had no effect on either ACE2 mRNA levels or ACE mRNA levels. Eplerenone, a mineralocorticoid receptor antagonist, completely blocked the increase in ACE mRNA levels and the reduction in ACE2 mRNA levels due to aldosterone. Conclusion Aldosterone, but not angiotensin II, reduced ACE2 mRNA levels and increased ACE mRNA levels in rat cardiomyocytes via mineralocorticoid receptor. Aldosterone might play an important role in cardiac remodeling by upregulating ACE and downregulating ACE2 levels. (Circ J 2008; 72: 1346 - 1350)

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Background Hereditary disordered cardiac muscle could be replaced with intact cardiomyocytes derived from genetically intact bone marrow (BM)-derived stem cells. Methods and Results Cardiomyopathic mice with targeted mutation of δ-sarcoglycan gene underwent intra-BM-BM transplantation (IBM-BMT) from transgenic mice expressing green fluorescence protein. The host BM and the peripheral blood were completely reconstituted by donor-derived hematopoietic cells by IBM-BMT. Treatment with granulocyte-colony stimulating factor (G-CSF) markedly increased donor-derived mesenchymal stem cells (MSC) in the BM and their mobilization into the peripheral blood after IBM-BMT. Treatment with isoproterenol (iso) for 7 days caused myocardial damage and left ventricular (LV) dysfunction in the cardiomyopathic mice. Co-treatment with iso and G-CSF increased donor BM cell recruitment to the heart and temporarily improved LV function in the cardiomyopathic mice with or without IBM-BMT. However, the cardiac muscle was not replaced with donor BM-derived cardiomyocytes in the cardiomyopathic mice with or without IBM-BMT, and this was associated with no improvement of LV function of mice aged 20 weeks. Conclusions These results suggest that G-CSF enhances engraftment of donor MSC in the BM and their mobilization into the peripheral circulation after IBM-BMT but MSC recruited to the heart do not differentiate into cardiomyocytes and do not repair the dystrophic heart. (Circ J 2008; 72: 1351 - 1358)

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Background The effects of chronic hypoxia on cardiac membrane fatty acids and on lipid peroxidation were examined, as well as the effect of l-carnitine (LCAR), which suppresses lipid peroxidation, on this process. Methods and Results Four-week-old Sprague-Dawley rats were exposed to 10% oxygen for 14 days ("Hypoxia"), and then to 100% oxygen for 12 h (O₂). LCAR (200 mg/kg) was administered by intraperitoneal injection daily for 2 weeks. Fatty acid composition, malondialdehyde (MDA) as a lipid peroxidation product, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase and catalase) were measured. The concentration of linoleic acid was lower, and that of docosahexaenoic acid, which has more double bonds than linoleic acid, was increased in hypoxic hearts. SOD activity decreased in hypoxia, whereas MDA was unchanged, but significantly increased in "Hypoxia"+O₂. LCAR reduced the increase in MDA, and had no effect on SOD activity or fatty acid composition. The administration of LCAR caused an increase in the ventricular levels of acetylcarnitine. Conclusions These results suggest that chronic hypoxia changes the cardiac fatty acid composition of juvenile rats to fatty acids that contain more double-bonds and reduce SOD activity, and that lipid peroxidation was augmented by exposure to oxygen. (Circ J 2008; 72: 1359 - 1366)

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Background In Japan, there is a symptom commonly referred to as "Hie-sho", which is a feeling of coldness or chill in a particular part of the body, and it can sometimes be unendurable. This phenomenon is known to occur more frequently in women. The present study used synchrotron radiation micro-angiography (SRMA) to examine the hypothesis that this feeling is derived from a sex difference in the vascular response to coldness. Methods and Results The hind limb of male (Group M) and female (Group F) Wistar rats was exposed to cold and the tissue temperature was recorded. SRMA with a spatial resolution of 26 μm was used to measure arterial diameter. The reduction in temperature brought on by cold exposure was significantly larger in Group F than in Group M (p<0.05). SRMA showed that the arteries were dilated by cold exposure in both groups; however, the percentage dilatation in response was statistically small in Group F (69±40%) compared with Group M (118±73%) (p<0.05). Conclusion Arteries in the limbs of female rats did not expand as much as those of the males in response to cold exposure, which may explain why women feel the cold more than men. (Circ J 2008; 72: 1367 - 1372)

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Reentrant bidirectional ventricular tachycardia (VT) with left bundle branch block (LBBB) configuration was diagnosed in a 54-year-old woman who showed 2 types of VT: QRS morphologies of LBBB with inferior axis and LBBB with superior axis. The development of VT with a superior axis was preceded by VT with inferior axis and/or both configurations of VT in alternate beats exhibiting bidirectional VT. The electrophysiological study demonstrated reproducible induction of both types of VT by programmed ventricular stimulation and both types of VT were entrained. Using conventional pace mapping and electro-anatomical mapping methods, radiofrequency energy applications at the 2 exit sites of the reentry path successfully terminated both types of VT and the patient was free from VT attacks for more than 15 months. (Circ J 2008; 72: 1373 - 1377)

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Two cases of catheter entrapment in the mitral valve, which is a rare complication of pulmonary vein isolation, were successfully treated via robot-assisted minimally invasive surgery. (Circ J 2008; 72: 1378 - 1380)

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A 57-year-old man with atrial tachycardia (AT) after cavo-tricuspid isthmus ablation underwent electrophysiological testing. Mapping revealed atrial activation with a cycle length exactly twice that of the P-P interval on electrocardiogram. Electroanatomic mapping revealed an AT focus near the left superior pulmonary vein, with inter-atrial conduction occurring in the lower septum and cavo-tricuspid isthmus conduction block. A propagation map demonstrated activation going down the left atrial posterior wall and right atrial free wall, generating different positive P waves in the inferior leads. The focal AT with inter- and intra-atrial conduction block exhibited widely-split P waves misinterpreted as a distinct AT. (Circ J 2008; 72: 1381 - 1384)

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Patients demonstrating critical limb ischemia with a long-distance occlusion of the major arteries are sometimes poor candidates for bypass surgery, because tandem occlusion complicates distal anastomoses and poor run-off causes early occlusion of bypass grafts. In order to resolve these problems, angiogenesis therapy was attempted by subcutaneous injection of granulocyte colony-stimulating factor either before or after peripheral bypass surgery in 2 cases. (Circ J 2008; 72: 1385 - 1387)

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