Background Limited information exists regarding the impact of gender on in-hospital outcome after primary stenting for acute myocardial infarction (AMI). Methods and Results A total of 2,981 patients (790 women and 2,191 men) participated in the study who were admitted within 24 h after symptom onset and underwent emergency primary stenting for AMI. Compared with men, women were significantly older; had higher incidences of hypertension, diabetes mellitus, hyperlipidemia, Killip class ≥2, and cardiogenic shock; had a higher blood glucose level and a lower serum creatinine level on admission. Other baseline characteristics, including the incidences of ST-segment elevation AMI, anterior infarction, 3-vessel disease, initial or final Thrombolysis in Myocardial Infarction (TIMI) flow grade did not significantly differ between the sexes. The in-hospital mortality rate was significantly higher in women than in men (9.4% vs 5.2%, p<0.001). On multivariate analysis, age, Killip class, blood glucose level, serum creatinine level, and final TIMI grade were independent predictors of in-hospital death, but female gender was not (odds ratio 1.01, p=0.69). Conclusions Our findings suggest that in patients undergoing primary stenting for AMI, women have higher in-hospital mortality than men, but female gender itself is not independently associated with increased in-hospital mortality after adjustment for baseline differences. (Circ J 2006; 70: 217 - 221)

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Background Many studies have examined sex-related differences in the clinical features of acute myocardial infarction (AMI). However, prospective studies are scant, and sex-related differences in symptoms of AMI remain unclear. We examined differences between men and women in terms of the clinical features of ST-segment elevation AMI. Methods and Results We studied 457 patients (106 women and 351 men) with ST-segment elevation AMI who were admitted within 24 h after symptom onset. The same cardiologist interviewed all patients within 48 h after admission. Women were older than men (72 vs 62 years, p<0.001) and had higher rates of hypertension (70 vs 56%, p=0.010), diabetes mellitus (36 vs 26%, p=0.047), and hyperlipidemia (51 vs 38%, p=0.019). Women were more likely than men to have non-specific symptoms (45 vs 34%, p=0.033), non-chest pain (pain in the jaw, throat, neck, shoulder, arm, hand, and back), mild pain (20 vs 7%, p<0.001), and nausea (49 vs 36%, p=0.013). On coronary angiography, the severity of coronary-artery lesions was similar in both sexes. In-hospital mortality was significantly higher in women than in men (6.6 vs 1.4%, p=0.003). Conclusions Clinical profiles and presentations differ between women and men with AMI. Women have less typical symptoms of AMI than men. (Circ J 2006; 70: 222 - 226)

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Background It has been well established that dyslipidemia is a significant risk factor for coronary artery disease (CAD), however, the association between fasting triglyceride (TG) and the occurrence of CAD is controversial. The objective of this study was to elucidate the relationship between fasting TG and CAD in middle-aged Japanese men. Methods and Results A cohort study of 6,966 middle-aged Japanese men (mean ± SD: 46.6±5.2 years) with a 10-year follow-up period was conducted to identify risk factors for the occurrence of CAD. One hundred and eleven cases of CAD were identified during the follow up. The Cox proportional hazard model was used to identify the independent risk factors for CAD. Adjustment was made for variables including age, body mass index, smoking habit, alcohol intake, duration of sleeping, systolic blood pressure, uric acid, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and TG. Fasting TG was identified as an independent risk factor for CAD. The adjusted hazard ratio of TG for CAD was 3.07 (95% confidence interval: 1.01-9.35, p<0.05). Additionally, a serum TG concentration level greater than 78 mg/dl was a significant risk for CAD. Conclusions By using the long term follow-up data of the study of middle-aged Japanese men, fasting TG was identified to be a significant risk factor for CAD. (Circ J 2006; 70: 227 - 231)

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Background The presence of intracoronary large thrombus burden (LTB) in the infarct-related artery increases the risk of distal embolization and no-reflow during percutaneous coronary intervention (PCI). Evaluation of whether the distal protection (DP) during primary PCI reduces adverse effects of LTB on myocardial reperfusion and infarct size was investigated. Methods and Results A consecutive series of 88 patients with acute myocardial infarction undergoing primary PCI using DP were compared with 81 consecutive patients treated by primary PCI alone. The DP use showed similar post-procedural myocardial blush grade (MBG)-3 and infarct size, but improved corrected thrombolysis in myocardial infarction frame count (cTFC) (29±11 vs 35±20, p=0.011) and the incidence of ST-segment resolution (80.7% vs 66.7%, p=0.038). In patients with LTB present, however, the DP use reduced occurrences of no-reflow (0% vs 11.8%, p=0.036) and distal embolization (4.8% vs 17.6%, p=0.129), resulting in higher occurrences of MBG-3 (61.9% vs 35.3%, p=0.021) and ST-segment resolution (78.6% vs 50.0%, p=0.009), lower cTFC values (30±8 vs 40±22, p=0.012) and smaller infarct size (12.2±11.2 vs 18.7±11.1, p=0.015). Conclusions With an improved myocardial reperfusion and smaller infarct size in patients with LTB, the DP during primary PCI might be a better strategy in this particular setting compared with conventional strategy. (Circ J 2006; 70: 232 - 238)

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Background Activated factor XIII (FXIII) cross-links between fibrin monomers, thus increasing the clot stability and resistance to fibrinolysis. Congenital FXIII deficiency causes severe bleeding diathesis. Recently, a common polymorphism of the FXIII A subunit (FXIII Val34Leu) has been identified as a protective factor against both arterial and venous thrombosis. The aim of this study was to investigate the role of FXIII Val34Leu polymorphism in coronary artery thrombosis, especially in young patients. Methods and Results One hundred and thirty patients under than 60 years of age with a history of myocardial infarction (%) and 130 healthy control subjects in the same age group were included to our study. Genomic DNA was extracted from venous blood samples and the polymerase chain reaction method was used to genotype FXIII Val34Leu polymorphism. Coronary risk factors such as obesity, diabetes mellitus, hyperlipidemia and smoking were compared between the groups with chi-square test and logistic regression analysis. The Leu allele frequency was significantly lower in patient group compared to control group (7.69% vs 19.23%, p=0.0001, chi-square). This difference was extremely significant in patients younger than 50 years-old (5.26% vs 19.64%, p<0.0001, chi-square). Conclusion Our findings support the hypothesis that Val34Leu polymorphism in FXIII gene has a protective effect against myocardial infarction. (Circ J 2006; 70: 239 - 242)

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Background Myocardial salvage after acute myocardial infarction (AMI) largely depends on the removal of infarct-related thrombus. Although both thrombolysis and thrombectomy are effective strategies to remove thrombus, there is a paucity of reports regarding the benefit of the combination therapy. Therefore, the efficacy of intravenous administration with mutant tissue plasminogen activator (Mt-PA) before thrombectomy and ordinary percutaneous coronary intervention (PCI) was evaluated. Methods and Results Consecutive 44 AMI patients without contraindication of Mt-PA were enrolled in the study and randomly assigned to thrombectomy with Mt-PA pre-administration (group T) or thrombectomy alone (group N). Although Thrombolysis in Myocardial Infarction (TIMI) grade before PCI and TIMI myocardial perfusion grade immediately after PCI were significantly greater in group T (p<0.05), there was no improvement of left ventricular ejection fraction immediately and 6 months after PCI. Conclusions These results suggest that intravenous administration with Mt-PA before thrombectomy had no significant benefit in the salvage of infracted myocardium over thrombectomy alone, despite improvement of coronary microcirculation immediately after PCI. (Circ J 2006; 70: 243 - 247)

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Background The estimation of coronary reperfusion in acute myocardial infarction (AMI) is important. The left ventricular (LV) Tei index is a noninvasive and sensitive parameter expressing overall LV function. We hypothesized that patients without good coronary reperfusion have worse LV function with a higher or worse Tei index compared to those with good reperfusion. Methods and Results In 85 patients with first anteroseptal AMI, without other cardiac lesions such as prior myocardial infarction, LV hypertrophy or valvular disease, the Tei index was measured using Doppler echocardiography immediately after patients' arrival to the hospital, and the Thrombolysis in Myocardial Infarction (TIMI) grade was evaluated through subsequent coronary angiography. The Tei index was significantly greater in patients who did not have TIMI score of 3 compared to those with a TIMI of 3 (0.60±0.13 vs 0.46±0.06, p<0.0001). A Tei index >0.50 as the criteria for the absence of TIMI 3 had the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 75, 86, 94, 54 and 78%, respectively. Conclusion An increased Tei index suggests the absence of adequate coronary reperfusion in patients with first anterior AMI without other lesion. (Circ J 2006; 70: 248 - 253)

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Background Exercise-induced ST-segment elevation is a relatively uncommon problem and occurs more frequently in patients who have had a myocardial infarction. Data is limited on the characteristics of Taiwanese patients without prior myocardial infarction who develop exercise-induced ST-segment elevation. Methods and Results Exercise-induced ST-segment elevation developed in 9 of 6,147 consecutive patients without myocardial infarction who underwent treadmill exercise testing at out institution over a 4-year period. The clinical and angiographic characteristics of these patients were studied. Angiographically normal coronary arteries with coronary vasospasm were found in 5 patients, hemodynamically significant coronary stenosis was found in 3 patients, and coexisting spasm in angiographically normal coronary arteries combined with hemodynamically significant coronary stenosis in the different vessel was found in 1 patient. During a median follow-up of 71 months, 2 patients with coronary vasospasm developed recurrent angina after self-discontinuation of calcium antagonists and 2 patients (1 with coronary vasospasm and 1 with hemodynamically significant coronary stenosis) died of cardiac causes before arrival at the emergency department. Conclusion Coronary vasospasm was a more common underlying pathology of exercise-induced ST-segment elevation in this Taiwanese cohort. Coronary angiography ± intracoronary ergonovine provocation testing is necessary in these patients to identify the underlying pathology and appropriate treatment. (Circ J 2006; 70: 254 - 261)

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Background Low birth weight has been associated with adult hypertension in several Western populations. This association needs to be evaluated in Japanese people. Methods and Results A population-based cross-sectional study of 3,107 subjects (2,303 males and 804 females) aged 35-66 years was conducted. The participants responded to a questionnaire about their birth weights, blood pressure, medical history, parental history, and lifestyle factors. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or under treatment by anti-hypertensives. Multiple logistic regression analysis adjusted for age, sex, body mass index, parental history, and lifestyle revealed the adjusted odds ratios for hypertension were 1.26 (95% confidence interval: 0.88-1.80), 1.00 (reference), 0.89 (0.73-1.08) and 0.70 (0.49-1.00) in subjects in birth weight categories of <2,500 g, 2,500-<3,000 g, 3,000-<3,500 g, 3,500- g, respectively (p-value for trend =0.009). Furthermore, this inverse association was clearly pronounced in normal-weight subjects. Conclusion Low birth weight was independently associated with adult hypertension in the Japanese workplace population. Our results support the inverse association observed previously in Western populations and suggest that intrauterine environmental insults might lead to permanent changes in the metabolism and structure of the fetal organs influencing the regulation of blood pressure. (Circ J 2006; 70: 262 - 267)

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Background Although electrophysiologic study (EPS) is one of the most reliable methods for selecting preventive therapy for patients with sustained ventricular tachycardia (VT), VT may recur during EPS-guided effective therapy; therefore, the importance of implantable cardioverter-defibrillator (ICD) has been emphasized. In this study, the prognoses of VT patients were evaluated to clarify the importance of EPS-guided therapy for the secondary prevention of VT. Methods and Results The study population consisted of 99 consecutive patients with a history of sustained VT, which was inducible in EPS. The VT induction protocol used 1-3 extrastimuli and rapid ventricular pacing at 2 right ventricular sites and included additional isoproterenol infusion. ICD implantation was applied to all patients with an episode of hemodynamically unstable VT, regardless of the result of preventive therapy. For preventive therapy, an antiarrhythmic drug and/or catheter ablation were selected, and they were defined as being effective in the EPS-guided therapy when the induction of VT was completely prevented. When no therapy was effective for prevention, an antiarrhythmic drug was prescribed under ICD implantation. During the follow-up period of 19±20 months, VT recurred in 17 of 32 patients (53%) in the ineffective group and in 10 of 67 patients (15%) in the effective group (p=0.0001). The therapies used in the effective group were class I antiarrhythmic drug in 9, class III in 15, and catheter ablation in 35 patients. Between the patients with and without VT recurrence, there were no significant differences in the left ventricular ejection fraction and the maximum number of repetitive ventricular responses that remained in VT induction in EPS. Conclusions Although VT may recur in up to 15% of patients with EPS-guided effective therapy, the recurrence rate was significantly reduced in comparison to that in the ineffective group. EPS-guided therapy may be useful to reduce the clinical recurrence of VT, as well as the action of ICD. (Circ J 2006; 70: 268 - 272)

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Background As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. Methods and Results The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6±2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. Conclusions Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures. (Circ J 2006; 70: 273 - 277)

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Background There remains to be issues regarding radiofrequency catheter ablation (RFCA) in pediatric patients that are different to those involving adults. This study was performed to determine the efficacy and safety of RFCA in pediatric patients. Methods and Results During the period from 1992 to 2003, 2,734 patients underwent RFCA and 131 pediatric patients who were ≤15 years old (70 males, mean age 12.0±3.1 years) were analyzed, retrospectively. The number of accessory pathways (APs) mediating atrioventricular re-entrant tachycardia was 93 (71.4%) and atrioventricular nodal re-entrant tachycardia (AVNRT) was 27 (20.5%). The most common indications for the RFCA were the `patient's choice' in 94 (71.2%) and `medically refractory tachycardia' in 29 (22.0%). The age-related indication of the `patient's choice' was 80.4% (82 of 102) for those >10 years old and 40.0% (12 of 30) for those ≤10 years old (p=0.01). RFCA was performed without sedation in 87.3% (89 of 102) of the subjects >10 years old as compared to 20.0% (6 of 30) of those ≤10 years old (p=0.01). The success rate was 92.8% (90 of 97 APs) for the ablation of APs, and 96.3% (26 of 27) for that of AVNRT. The overall complication rate was 3.8% (5 of 131). During a mean follow-up duration of 13.1±2.5 months, the freedom of recurrence was 87.8% (79 of 90) for the arrhythmia associated with APs and 92.3% (24 of 26) for AVNRT. Conclusion RFCA in pediatric patients had a good success rate with acceptable recurrence and complication rates when compared to adult patient results. Therefore, RFCA could be considered as the first line of therapy for arrhythmias with concealed and manifested APs and AVNRT in pediatric patients. (Circ J 2006; 70: 278 - 284)

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Background Two-dimensional (D) echocardiography-derived left atrial (LA) volume has been shown to provide a more accurate assessment of LA size than the M-mode LA dimension. Our objective was to provide reference ranges of LA volume in healthy Japanese adults. Methods and Results The study subjects consisted of 105 Japanese adults, with a mean age of 39±13 years (range 20-63 years old). All subjects had normal ejection fraction (>55%), no wall motion abnormalities, normal diastolic function, no valvular disease, and normal sinus rhythm. The maximum LA volume, at left ventricular end-systole just before the opening of the mitral valve, was measured by using the bi-apical (4- and 2-chamber views) Simpson's rule. Both the absolute LA volume and the volume corrected by body surface area (LA volume index) were obtained. The LA volume ranged from 21 to 53 ml (mean 37±8 ml) and the LA volume index ranged from 13 to 30 ml/m² (mean 22±4 ml/m²). The mean LA volume index + 2SDs was 30 ml/m². Conclusions Recognition of the upper limits of LA volume in normal Japanese subjects is of particular clinical relevance because it offers the opportunity of pathological LA remodeling diagnosis. (Circ J 2006; 70: 285 - 288)

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Background The aim of the present study was to assess the accuracy and efficiency of left ventricular ejection fraction (LVEF) analysis by multidetector row computed tomography (CT). Methods and Results The CT data of 21 patients were analyzed by semi-automated software on a workstation. In analysis of LVEF using systolic volumes in the 6 phases (30-55%), systolic images of 10% interval (35, 45, 55%) were underestimated with a mean measurement error of -0.4% and the standard error of the estimate (SEE) of 0.6%, compared with the LVEF using images of 5% interval. In analysis of LVEF using 3-slice thicknesses of axial images (1, 2, and 3 mm), and 3-slice numbers of short-axis sections (10 14, and 30 slices), there was no significant difference between the SEE of the intraobserver reproducibility and that of the analysis with 30 short-axis sections using axial images of 1-, 2- and 3-mm thickness, and that with 14 short-axis sections using axial images of 1- and 2-mm thickness. The mean analysis times were 96.9 s, 119.8 s, and 227.0 s for the analysis with 10, 14, and 30 short-axis sections, respectively. Conclusion The proper selection of the reconstruction interval in the cardiac phase, the slice thickness of the axial images, and the number of short-axis sections reduces the analysis time, maintaining the accuracy of LVEF analysis. This will be acceptable for practical use at present, although more accurate analysis is preferable. (Circ J 2006; 70: 289 - 296)

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Background The predictors and lesion morphology of patients with ischemic heart disease testing false negative results in stress myocardial perfusion single-photon emission computed tomography (SPECT) was investigated. Methods and Results Subjects were 58 consecutive patients who underwent coronary angiography (CAG), even though they showed normal findings in stress myocardial perfusion SPECT. Age, gender, methods of stress, perfusion agent, coronary risk factors, angina symptoms, and electrocardiographic changes were investigated as predictors by multivariate analysis. For lesion morphology, significant stenotic lesions were studied for morphological characteristics and reference diameter (RD), percentage diameter stenosis (%DS), minimum lumen diameter (MLD), and lesion length (LL) were measured. CAG revealed 30 significant stenotic lesions in 18 patients. Logistic regression analysis revealed significant predictors to be age (odds ratio (OR) 1.118, p<0.05), typical anginal pain (OR 21.09, p<0.01), and hypertension (OR 8.336, p<0.05). For lesion morphology, there were only 2 diffuse lesions and the mean RD, %DS, MLD, and LL were 3.03±0.9 mm, 63.1 ±9.3%, 1.13±0.49 mm, and 13.2±7.0 mm, respectively. Conclusion Sufficient caution is believed necessary in the interpretation of normal findings of stress myocardial perfusion SPECT when the patient is elderly, complains of typical anginal pain, or has hypertension. In regard to characteristics of lesion morphology, there were hardly any diffuse lesions. (Circ J 2006; 70: 297 - 303)

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Background Increased arterial stiffness has been shown to be associated with coronary heart disease (CHD). However, it remains unclear as to whether the second derivative of the finger photoplethysmogram (SDPTG), a non-invasive method for the assessment of arterial stiffness, is useful for the estimation of risk of CHD in the general population. Methods and Results The SDPTG in 211 subjects (age: 63±15 years, range: 21-91 years, 93 males) was recorded without apparent atherosclerotic disorders from a community. The relationship between the SDPTG indices (b/a and d/a) and coronary risk factors (n=211) or the Framingham risk score (n=158, age: 60±12 years, range: 30-74 years, 63 males) were analyzed. The SDPTG indices significantly correlated with the Framingham risk score in both genders (b/a; r_male =0.43, r_female =0.54 and d/a; r_male =-0.38, r_female =-0.58), as well as several coronary risk factors. In the receiver operating characteristics curve analyses, the b/a discriminated high-risk subjects for CHD, who were in the highest quintile of the Framingham risk score in each gender, with a sensitivity and specificity of 0.85 and 0.58 in males and 0.83 and 0.72 in females, respectively. Conclusions These results suggest that the SDPTG is useful for the estimation of risk of CHD in the general population. (Circ J 2006; 70: 304 - 310)

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Background The diagnosis of endothelial dysfunction has been gaining clinical importance, but although endothelial function testing is available in the research setting, no technique yet exists that is simple, safe, reproducible and easily performed as a clinical screening method. The aim of this study was to design a new, scintigraphic method of imaging the flow-mediated dilation in the forearm, which represents the functional characteristic of endothelial dysfunction. Methods and Results The study group comprised 118 subjects in whom left forearm ischemia was induced by inflating a sphygmomanometer cuff to supra systolic pressure for 4.5 min. Later, dynamic acquisition (2 s frame/min) was initiated after the injection of technetium-99m methoxy-isobutyl isonitril into the dorsal pedal veins. Equivalent regions of interest were drawn on both arms to detect total activity counts during 1 min and the perfusion ratios (left arm/right arm) were calculated. The left arm counts (22,203.3±12,372.7) were significantly higher than the right arm counts (9,980.9±5,931.9) (p<0.001). A significant decrease in perfusion ratios was noted in the hypertension and hypercholesterolemia groups. An increase in the number of risk factors caused an insignificant decrease in perfusion ratio (p=0.346). Conclusion Non-invasive evaluation of endothelium-dependent vasodilation by semiquantitative scintigraphic method using radioactive perfusion tracer provided promising results. (Circ J 2006; 70: 311 - 315)

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Background Implantable cardioverter-defibrillators (ICDs) are the most effective therapy in reducing the mortality of patients with life-threatening ventricular tachyarrhythmias. However, the ICD cannot prevent the recurrence of tachycarida attacks and that limits the clinical usefulness of them. The Nippon ICD Plus Pharmachologic Option Necessity (NIPPON) trial was designed as the first prospective randomized study to test the hypothesis whether amiodarone could improve the patient's clinical outcome by reducing the amount of ICD therapy in the Japanese patient population. Methods and Results Approximately 400 patients with organic heart disease and spontaneous episode(s) of sustained ventricular tachycardia/fibrillation (VT/VF) will be randomly assigned to one of 2 groups; the amiodarone group and non-amiodarone group. Both groups of patients will be followed at least for 24 months. The end-point committee will adjudicate events in a blinded fashion. The primary end-points of this study are determination of the appropriate therapy from the ICD and alteration of the assigned treatment because of its harmful effects and/or frequent ICD therapies. Conclusion The NIPPON study is expected to confirm our understanding of the prognostic and therapeutic usefulness of adjuvant amiodarone therapy for patients with an ICD and with a history of sustained VT/VF. (Circ J 2006; 70: 316 - 320)

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Background The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca²⁺ overload was investigated. Methods and Results The mitochondrial oxygen consumption (mVO₂) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca²⁺ overload from 10 to 100 μmol/L augmented mVO₂ was from 527±139 to 671 ±138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 μmol/L), but not by metoprolol (100 μmol/L). Ca²⁺ overload augmented the ROS production upon complex I injury (9.7±1.2 to 11.4±1.4 nmol/mg, p<0.05). Carvedilol dose-dependently suppressed this ROS production, whereas metoprolol did not. Conclusions Carvedilol, but not metoprolol, was thus found to inhibit the calcium-dependent augmentation of mVO₂ and ROS production upon complex I injury. This new effect of carvedilol might partly explain the beneficial effect of carvedilol for the treatment of heart failure. (Circ J 2006; 70: 321 - 326)

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Background It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. Methods and Results Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. Conclusions Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to β adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments. (Circ J 2006; 70: 327 - 334)

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Background Stimulation of angiotensin II type 1 (AT₁) receptors has been shown to generate the arrhythmogenic substrate in ventricular hypertrophy. We examined whether candesartan, an AT1 receptor blocker, has antiarrhythmic effects on mouse model of left ventricular hypertrophy created by transverse aorta constriction (TAC). Methods and Results Forty-eight male mice were divided into 3 groups: TAC, candesartan (TAC plus candesartan) and control groups. Echocardiographic examination was performed before the operation and 2 and 4 weeks after the operation. Four weeks after the operation, electrophysiological studies were conducted by inserting a 1.7 F octapolar electrode catheter through the right external jugular vein into the right ventricle. The effective refractory period of the atrioventricular node (AVNERP) in TAC group was significantly prolonged, and short episodes of ventricular tachycardia (VT) and atrial fibrillation (AF) could be induced in 12 of 16 mice (75%) and 8 of 16 (50%), respectively. In contrast, in candesartan group, the incidence of VT was significantly reduced (12.5%) and no AF was induced. Moreover, the drug produced a significant left ventricular hypertrophy regression and restored the AVNERP to normal. Conclusions Candesartan reduced both ventricular and atrial arrhythmias in the TAC mice, presumably by preventing the electrical remodeling by inhibiting the AT₁ receptor. (Circ J 2006; 70: 335 - 341)

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Background Monocyte chemoattractant protein-1 (MCP-1) and its major receptor, CC chemokine receptor 2 (CCR2), have been shown to contribute to left ventricular remodeling after myocardial infarction. However, it is unknown whether CCR2 deficiency protects the myocardium after myocardial ischemia-reperfusion. The purpose of the present study was to investigate the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Methods and Results Experiments were performed in CCR2^-/- and wild-type mice subjected to 45 min of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesions was markedly reduced in CCR2^-/- mice compared with wild-type mice (p<0.01). The infarct size was significantly reduced in CCR2^-/- mice compared with wild-type mice at 3 days after reperfusion (p<0.001). In situ zymography revealed augmented gelatinolytic activity at 3 days after reperfusion in wild-type mice, but significantly less activity in CCR2^-/- mice. NADPH oxidase activity, the intensity of nitrotyrosine staining and expression of inducible nitric oxide synthase and thioredoxin-1 were significantly increased in ischemic myocardium in wild-type mice compared with CCR2^-/- mice, indicating a role for CCR2 in oxidative stress after ischemia-reperfusion. Conclusions Inhibition of the MCP-1/CCR2 pathway may be a useful strategy for attenuating myocardial ischemia-reperfusion injury. (Circ J 2006; 70: 342 - 351)

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Background The incidence of atrial fibrillation (AF) increases with aging, but the aging-associated electrophysiological changes of atrial myocardium are poorly understood. Methods and Results Based on the hypothesis that aging of the atrium enhances AF susceptibility, 30 Wistar rats were divided into 3 age groups: adult, middle-aged, and aged (n=20 per group). Their hearts were isolated and perfused by Langendorff apparatus. Monophasic action potential duration at 90% repolarization (MAPD₉₀) and effective refractory period (ERP) at the basic stimulation cycle length (BCL: 400 ms), and MAPD₉₀ at other different stimulation cycle lengths in each age group were measured. At the BCL, the MAPD ₉₀ of the right atrial myocardium was prolonged from the adult to the aged group, that of the left atrial myocardium was prolonged from the adult to middle-aged group, and the MAPD₉₀ of the left atrial myocardium in the aged group were shorter than that in the adult and middle-aged groups. The ERP of the atrial myocardium showed the same age-associated trend as MAPD₉₀. As the stimulation frequency increased, the MAPD₉₀ of both the left and right atrial myocardium shortened correspondingly in the adult and middle-aged groups, but in the aged group the MAPD₉₀ of the right atrial myocardium shortened markedly more than that of the left atrial myocardium. Conclusions There are different aging-associated electrophysiological changes in the right and left atrium, and the older heart is more vulnerable to developing the substrate for AF. (Circ J 2006; 70: 352 - 357)

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A case of acute pleuropericarditis, which occurred after apparently successful percutaneous coronary intervention (PCI) for chronic total occlusion of the right coronary artery, is reported. The patient underwent coronary stenting without any immediate signs of complications. However, he had an acute onset of chest pain with fever which happened 4 h after PCI. He was diagnosed with acute pleuropericarditis by blood tests, electrocardiogram, chest X-ray, and echocardiogram. He rapidly recovered by intravenous hydrocortisone followed by oral prednisone administrations and percutaneous catheter pericardial drainage. Acute pleuropericarditis relevant to post-cardiac injury syndrome with an atypically early onset might have occurred in this case as a rare complication of PCI. (Circ J 2006; 70: 358 - 361)

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Background There are few biological markers, which strictly show the severity of congestive heart failure (CHF). Methods and Results Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). Conclusions The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients. (Circ J 2006; 70: 362 - 363)

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