In order to clarify the time course of left ventricular (LV) wall motion in patients with anterior acute myocardial infarction (AMI) showing terminal QRS distortion on the admission electrocardiogram (ECG), the present study examined 106 patients with their first anterior AMI (≤6 h) who underwent emergency coronary arteriography and cardiac cathetherization at 1 and 6 months after the infarction. The patients were classified into 2 groups according to the presence (group A, n=23) or absence (group B, n=83) of terminal QRS distortion (emergence of the J point at ≥50% of the R-wave amplitude in leads with QR configuration and/or absence of S waves in leads with RS configuration) on the admission ECG. Group A had a lower LV ejection fraction and more reduced regional wall motion (RWM) in the infarct region at both 1 and 6 months after AMI than group B. The degree of improvement in RWM between 1 and 6 months after AMI was less in group A than in group B (−0.1 ±0.5 vs 0.4±0.6 SD/chord, p<0.01). This study indicates that patients with anterior AMI showing terminal QRS distortion on the admission ECG have more severely depressed LV wall motion and less improvement in RWM in the infarct region in the healing stage, suggesting that this sign is an indicator of severe myocardial damage. (Jpn Circ J 2001; 65: 63 - 66)

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The present study investigated the relationship between myocardial damage and C-reactive protein (CRP) levels, with no increase in creatine kinase (CK) activity, immediately after the onset of acute myocardial infarction (AMI) in 85 patients with their first reperfused anterior AMI without CK elevation on admission and no ischemic events during hospitalization. Patients were classified into those with low levels (<0.3 mg/dl) of CRP (Group L; n=67) and those with high levels (≥0.3 mg/dl) of CRP (Group H; n=18). Group H had a higher proportion of patients with a history of preinfarction angina (89 vs 55%, p<0.01), especially unstable angina. ΣST in leads V_1-6 on admission ECG was lower in Group H than in Group L (14±7 vs 21±13 mm, p<0.05). Predischarge left ventriculography showed that the left ventricular global ejection fraction (55±11 vs 48±10%, p<0.01) and SD/chord at the left anterior descending artery lesion (-1.7±0.9 vs -2.3±0.9, p<0.01) were better in Group H. Multivariate analysis demonstrated that both CRP on admission (p=0.011) and preinfarction angina (p=0.002) were independently associated with better regional wall motion (SD/chord >−2.0) before discharge. These results suggest that the clinical situation of elevated CRP immediately after onset is associated with less myocardial damage and better left ventricular function in reperfused anterior AMI. (Jpn Circ J 2001; 65: 67 - 70)

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This study investigated the clinical significance of matrix metalloproteinases (MMPs) in acute myocardial infarction (AMI) and the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of MMPs in AMI. Forty patients with AMI were recruited. Plasma and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. Levels of MMP-1 and MMP-2 were measured by enzyme-linked immunosorbent assay. The MMP-1 level in the culture medium of PBMCs after incubation for 24 h was designated as `PBMC-MMP-1 level.' Plasma MMP-1 did not significantly change during the course of AMI, but the plasma MMP-2 levels increased gradually after the onset of AMI with maximum elevation on day 21 after onset. Plasma MMP-2 activity also became significantly elevated during the course of AMI. PBMC-MMP-1 levels in the patients were significantly higher than those in control subjects over the course of AMI. Significant positive correlations were observed between maximum PBMC-MMP-1 levels and maximum plasma C-reactive protein levels (r=+0.55, p<0.01) and left ventricular end-diastolic volume index (r=+0.63, p<0.001). In conclusion, plasma MMP-2 levels and activity and MMP-1 production by PBMCs are increased in patients with AMI. Inflammation after AMI may enhance production of MMP-1 by PBMCs. These changes may play an important role in the ventricular remodeling that occurs after AMI by promoting the degradation of the extracellular matrix. (Jpn Circ J 2001; 65: 71 - 75)

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Predicting sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM) is difficult, so the present study evaluated the efficacy of microvolt-level T-wave alternans (TWA) and compared it with conventional parameters for prospective risk stratification of SCD in patients with DCM. Eighty-two patients with DCM (53±15 years old, 67 M/15 F) underwent assessment of TWA, left ventricular end-diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), signal-averaged ECG, and analysis of 24-h Holter monitoring and QT dispersion (QTd). The endpoint of the study was defined as either SCD or documented sustained ventricular tachycardia/ventricular fibrillation (SVT/VF) during the follow-up period. During an average follow-up period of 24 months, 1 patient died suddenly and 9 patients had SVT/VF. Kaplan-Meier survival analysis showed that TWA, LVEF (≤35%), nonsustained ventricular tachycardia, and QTd (>90 ms) were significant univariate risk stratifiers (p<0.005, p<0.005, p<0.005, and p<0.05, respectively). Multivariate Cox regression analysis showed that TWA and the LVEF were statistically significant independent risk stratifiers (p<0.05 and p<0.01, respectively). A combination of TWA and LVEF identified high risk DCM patients (p<0.01); TWA for the electrical substrate and the LVEF for the hemodynamic function. (Jpn Circ J 2001; 65: 76 - 80)

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It has been reported that coronary endothelial dysfunction is associated with the pathogenesis of coronary spasm, and that endothelial nitric oxide (NO) mediated vasodilatation was decreased in coronary epicardial arteries in patients with coronary spastic angina (CSA). However, there are few reports about the endothelial function in peripheral resistance vessels of patients with CSA, so the present study investigated the role of NO in forearm resistance vessels in such patients. The responses of forearm blood flow to acetylcholine (ACh; 8-24 μg/min) and sodium nitroprusside (SNP; 0.4-1.2 μg/ml) infusions was examined using plethysmography, and subsequently the responses to ACh after an infusion of NG-monomethyl-L-arginine (L-NMMA; 4 μmol/min, for 5 min) in 17 patients with CSA and 17 age- and sex- matched controls. The vasodilator responses to ACh and SNP were comparable between the 2 groups (p=NS). L-NMMA significantly suppressed the vasodilator responses to ACh in controls (p<0.05), but there was no significant difference in the responses to ACh before and after infusion of L-NMMA in patients with CSA (p=NS). These results indicate that endothelial NO-mediated vasodilatation is decreased in the forearm resistance vessels of patients with CSA. (Jpn Circ J 2001; 65: 81 - 86)

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A new 2-week hospitalized phase II cardiac rehabilitation program has been designed and the present study sought to clarify whether the physical and psychological status of patients with acute myocardial infarction (AMI) improved after participation in the program. Fifty-one patients with AMI were enrolled in the rehabilitation program, which consisted of exercise training, education and counselling, and another 34 patients with AMI who did not participate in the program served as the control group. The physical and psychological status of the patients was evaluated before, at 1-month after the program, and at 6- and 12-months follow-ups. The physical status was assessed by exercise tolerance and serum lipid profiles and the psychological status was assessed by the Spielberger State - Trait anxiety inventory questionnaire (STAI) and self-rating questionnaire for depression. Quality of life (QOL) was assessed using established and validated QOL scales. After participation in the program, the exercise tolerance, serum lipid profiles and STAI anxiety score of the patients were improved significantly and at the 6-month follow-up these parameters remained improved and regular physical activity was maintained. The QOL score also improved significantly. Even at the 12-month follow-up, lipid profiles remained improved and regular physical activity was maintained. The 2-week hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and psychological status in patients with myocardial infarction (MI). It provides beneficial effects on the patient's physical and psychological activities in the recovery phase and may also contribute to the secondary prevention of MI. (Jpn Circ J 2001; 65: 87 - 93)

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Because large thrombus is a limitation for revascularization in acute myocardial infarction (AMI), the present study evaluated the effectiveness of pulse infusion thrombolysis (PIT) in patients with an AMI with a large (>15 mm) coronary thrombus, focusing on the occurrence of the `no flow' phenomenon. The retrospective study compared patients treated before (1988-95; Group A, n=74) and after (1996-99; Group B, n=40) the use of PIT, using the following parameters: lesion success (<50% stenosis during 30-min observation), procedural success (lesion success plus TIMI grade 3 flow), procedural no flow (TIMI grade 0 flow during the procedure with `back and forth movement' of contrast dye after lesion success), persistent no flow (consistent no flow without any flow improvement at the final visualization despite intensive treatment), reocclusion rate and in-hospital death. Group B was significantly better than Group A in procedural success (90% vs 66%; p=0.005), procedural `no flow' (51% vs 15%; p<0.001), and persistent `no flow' (34% vs 10%; p<0.05). Subgroup comparison was performed among the following groups: Direct-BA group (n=44): treated with mechanical angioplasty alone; ICT-BA group (n=40): treated with prior intracoronary thrombolysis and angioplasty; and PIT-BA group (n=30): treated with PIT and angioplasty. There were no differences in thrombus length and lesion success among these 3 groups. Procedural success was best achieved in PIT-BA: 97% vs 52% for Direct-BA (p=0.003) and 68% for ICT-BA (p=0.009). Procedural `no flow' was least in PIT-BA: 50% vs 3.3% for Direct-BA (p=0.003) and 25% vs 3.3% for ICT-BA (p=0.042). Persistent `no flow' was less frequent in PIT-BA than Direct-BA: 32% vs 3.3% (p=0.009). However, the difference between ICT-BA and Direct-BA was insignificant: 13% vs 3.3% (p=0.53). There were no differences in reocclusion rate and in-hospital death among the 3 subgroups. And there were no differences between Direct-BA and ICT-BA in any parameters. PIT was effective in preventing `no flow' in the mechanical revasculalization for AMI especially those cases with a large thrombus. (Jpn Circ J 2001; 65: 94 - 98)

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The pathomorphologic mechanism responsible for abnormal perfusion imaging during thallium-201 myocardial single photon emission computed tomography (²⁰¹Tl-SPECT) in patients with Duchenne's progressive muscular dystrophy (DMD) was investigated. Hearts from 7 patients with DMD were evaluated histopathologically at autopsy and the results correlated with findings on initial and delayed resting ²⁰¹Tl-SPECT images. The location of segments with perfusion defects correlated with the histopathologically abnormal segments in the hearts. Both the extent and degree of myocardial fibrosis were severe, especially in the posterolateral segment of the left ventricle. Severe transmural fibrosis and severe fatty infiltration were common in segments with perfusion defects. In areas of redistribution, the degree of fibrosis appeared to be greater than in areas of normal perfusion; and intermuscular edema was prominent. Thus, the degree and extent of perfusion defects detected by ²⁰¹Tl-SPECT were compatible with the histopathology. The presence of the redistribution phenomenon may indicate ongoing fibrosis. Initial and delayed resting ²⁰¹Tl-SPECT images can predict the site and progress of myocardial degeneration in patients with DMD. (Jpn Circ J 2001; 65: 99 - 105)

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Autoimmne mechanisms have been implicated in the pathogenesis of chronic ongoing mycarditis. An earlier study of murine chronic ongoing myocarditis reported that infiltrating T cells and macrophages were prominent in the normal donor heart, in a heterotopic cardiac transplantation model. It was demonstrated that myocarditis was transferred to a normal heart transplanted into a mouse with chronic myocarditis. The present study investigated an autoimmune link to the pathogenesis of chronic ongoing myocarditis by analyzing the T cell clonalities in the model. To characterize the accumulating T cells in the donor heart, the T cell receptor β genes (TCRBG) were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) from mRNA in the donor hearts and accumulating TCRBG clonotypes were contrasted with those from recipient hearts. Inbred 3-week-old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain), 2×10⁴ PFU, and housed for more than 60 days. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis, as well as into the mice with chronic ongoing myocarditis. Both recipient and donor hearts were evaluated histologically 2 weeks after the transplantation. TCRBG were amplified by RT-PCR from mRNA of recipient and donor hearts and spleens. The specific accumulating TCRBG clonotypes were identified by their single strand conformation polymorphism. Multiple clonotypic accumulations occurred in the donor heart after cardiac transplantation. Distinct oligoclonal accumulation of TCR Vβ1, 10, and 13 T cells was found in both recipient and donor hearts in 3 of 4 mice. Moreover, these clonotypes were not observed in spleen cells of the recipient mice. T specific cells expanding clonotypes of TCRBG are responsible for transferring myocarditis to the donor heart. An autoimmune response may, therefore, play a key role in the progression of chronic ongoing myocarditis. (Jpn Circ J 2001; 65: 106 - 110)

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Atrial fibrillation (AF) is often described as a disorganized phenomenon, but many features that qualitatively suggest an underlying order have recently been reported. The present study aimed to disclose this underlying order of AF in a quantitative manner, using a new method of mutual information (MI), which is a measure for gauging the general correlation between 2 time series. Frequency analysis and the MI method were used to analyze 5 epicardial potentials on both atria during AF induced by vagal stimulation (Vs) in 15 dogs. Unipolar electrodes were placed on the right atrial appendage (Rap), the high right atrium (HRA), and the left atrial appendage (Lap). The other 2 electrodes were placed equidistantly between HRA and Rap (RA1 - RA2). The power spectrum of AF had a discrete peak around 17 Hz during Vs. After Vs was stopped, the discrete peak shifted from 17 Hz to 7 Hz on all epicardial leads. Taking RA2 as a reference, MI was calculated between RA2 and each of the other electrodes. The MI values (0.066±0.005) were greater than 0.047 (the critical value for correlated data) even during Vs. The MI values increased significantly from the highly active process of AF during Vs to the less active one (0.126±0.006) before termination of AF. In addition, the MI values increased more at the electrodes close to RA2 (RA1 and Rap) than at those far from it (HRA and Lap). These findings suggest that multiple wavelets, which are not random, progressively organize into a few major waves toward the termination of AF; therefore, AF is not a random phenomenon in this model. (Jpn Circ J 2001; 65: 111 - 116)

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Both hypercholesterolemia and vascular injury have been reported to induce macrophage infiltration, but their combined effect and the mechanism by which hypercholesterolemia enhances the infiltration remain to be clarified in vivo. To evaluate the effect of hypercholesterolemia on macrophage infiltration after vascular injury, the iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 2 h, 1 day, 3 days, 7 days, and 14 days after balloon injury using immunohistochemical staining for macrophages, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Nuclear factor kappa-B (NF-κB) activation was also evaluated in fresh frozen iliac arteries using the electrophoretic mobility shift assay method. The fundamental difference between HC and NC was the amount of macrophage infiltration seen in HC from 7 days after balloon injury. Two out of 4 HC iliac arteries on the 7th day, and 3 out of 4 HC iliac arteries on the 14th day were positively stained with ICAM-1 in regenerated endothelium and neointima, whereas there were no positively stained NC iliac arteries. Neither HC nor NC tissues showed positive staining with VCAM-1. NF-κB was activated in HC 7 and 14 days after balloon injury, but not in NC. In conclusion, in vivo hypercholesterolemia induces macrophage infiltration after balloon injury and it is mediated by increased NF-κB activation promoting ICAM-1 expression. (Jpn Circ J 2001; 65: 117 - 122)

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While studying flow-dependent coronary dilation using a Doppler flow velocity guidewire, total occlusion of a stenosed segment of the left circumflex artery during the intracoronary infusion of bradykinin was angiographically documented. Total occlusion was not demonstrated during intracoronary infusion of bradykinin after angioplasty. This is angiographic confirmation of the coronary steal phenomenon that has been previously described in the field of stress scintigraphy. (Jpn Circ J 2001; 65: 123 - 125)

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Most patients diagnosed with secondary hemochromatosis have had repeated blood transfusions. Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure. A 23-year-old woman with hemochromatosis had, despite significant left ventricular dysfunction, liver function within the normal range on biochemical evaluation. She was treated for congestive heart failure and given desferoxamine intravenously. She did not have primary hemochromatosis, and had not received multiple blood transfusions or iron supplement. As a child the patient had been diagnosed with congenital non-spherocytic hemolytic anemia not requiring transfusion; thus, this is a unique case of secondary hemochromatosis. (Jpn Circ J 2001; 65: 126 - 128)

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The present case is a 64 year-old man in whom transient but marked ST elevation was confirmed in the contralateral precordial leads (V_1-3) during percutaneous transluminal coronary angioplasty (PTCA) of the proximal right coronary artery, suggesting that the patient had anteroseptal ischemia. The ST elevation persisted even after the balloon was deflated, and no changes in the left coronary artery were detected. In addition, blood flow in the affected area of the right coronary artery was favorable and there was a transient delay only in the right ventricular branch. Once blood flow in the right ventricular branch improved, ST returned to baseline, and when the right ventricular branch was again occluded by the balloon, ST elevation occurred in a reproducible manner. Hence, the electrocardiographic changes in the precordial leads were caused by occlusion of the right ventricular branch. It is rare to observe ST elevation caused by isolated right ventricular branch ischemia. (Jpn Circ J 2001; 65: 129 - 131)

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This report describes an adult patient with Noonan syndrome accompanied by biventricular hypertrophic cardiomyopathy causing isolated right ventricular outflow tract obstruction. Biventricular hypertrophic cardiomyopathy causing right- and/or left-side outflow tract obstruction, as well as valvular pulmonary stenosis, is relatively common in infants with Noonan syndrome. However, this condition without a dysplastic pulmonary valve, or indeed any polyvalvular dysplasia, is rare in adults with Noonan syndrome. Treatment with a β-adrenergic receptor blocking agent improved the patient's symptoms. Because neither the etiologic and prognostic relationship nor the genetic linkage between hypertrophic cardiomyopathy associated with Noonan syndrome and non-syndromic hypertrophic cardiomyopathy is clearly defined, clinicopathological findings and further follow-up may provide important evidence for the pathogenesis of hypertrophic cardiomyopathy. (Jpn Circ J 2001; 65: 132 - 135)

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Immunohistochemical staining of human atherosclerotic plaques revealed expression of the tumor necrosis factor receptor superfamily (TNFRSF) 12 in regions rich in macrophage/foam cells. The role of TNFRSF12 in the functioning of monocytes in relation to atherogenesis was investigated by analysis of cellular events after stimulation of TNFRSF12 in a human macrophage-like cell line, THP-1. Activation of the THP-1 cells on plates coated with monoclonal antibody against TNFRSF12 induced the expression of matrix metalloproteinases (MMPs) -1, -9, and -13. Furthermore, the expression patterns of TNFRSF12 and the MMPs overlapped in atherosclerotic plaques. Signaling of TNFRSF12 may thus contribute to the induction of extracellular matrix degrading enzymes in macrophages. (Jpn Circ J 2001; 65: 136 - 138)

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