[Association between function of selenium and heart disease].

An excessive oxidative stress is considered to be responsible for the development and progression of heart disease. Deficiency of trace elements with antioxidative activities is present in patients with heart disease. Selenium (Se) is an integral part of the enzyme glutathione peroxidase(GPx), one of the central players of the heart's antioxidant system, and it's deficiency is implicated in certain types of heart disease. Our study suggests that myocardial oxidative stress in chronic heart failure may be augmented at least in part by concomitant GPx deficiency, and that the administration of Se could rescue the exhaustion of this selenoprotein, resulting in improved left ventricular function.

Impact of linked color imaging and blue laser imaging on the diagnosis of esophageal squamous cell carcinoma in iodine unstained areas.

The pink color sign in iodine unstained areas is useful to differentiate esophageal squamous cell carcinoma (ESCC) from other lesions. However, some ESCCs have obscure color findings which affect the ability of endoscopists to differentiate these lesions and determine the resection line. Using white light imaging (WLI), linked color imaging (LCI) and blue laser imaging (BLI), 40 early ESCCs were retrospectively evaluated using images before and after iodine staining. Visibility scores for ESCC by expert and non-expert endoscopists were compared using these three modalities and color differences measured for malignant lesions and surrounding mucosa. BLI had the highest score and color difference without iodine staining. Each determination with iodine was much higher than without iodine regardless of the modality. With iodine, ESCC mainly appeared pink, purple and green using WLI, LCI and BLI, respectively and visibility scores determined by non-experts and experts were significantly higher for LCI (both p < 0.001) and BLI (p = 0.018 and p < 0.001) than for WLI. The score with LCI was significantly higher than with BLI among non-experts (p = 0.035). With iodine, the color difference using LCI was twice that with WLI and one with BLI was significantly larger than with WLI (p < 0.001). These greater tendencies were found regardless of location, depth of cancer or intensity of pink color using WLI. In conclusion, areas of ESCC unstained by iodine were easily recognized using LCI and BLI. Visibility of these lesions is excellent even by non-expert endoscopists, suggesting that this method is useful to diagnose ESCC and determine the resection line.

Low-field magnetoelectric effect at room temperature.

The discoveries of gigantic ferroelectric polarization in BiFeO(3) (ref. 1) and ferroelectricity accompanied by a magnetic order in TbMnO(3) (ref. 2) have renewed interest in research on magnetoelectric multiferroics, materials in which magnetic and ferroelectric orders coexist, from both fundamental and technological points of view. Among several different types of magnetoelectric multiferroic, magnetically induced ferroelectrics in which ferroelectricity is induced by complex magnetic orders, such as spiral orders, exhibit giant magnetoelectric effects, remarkable changes in electric polarization in response to a magnetic field. Many magnetically induced ferroelectrics showing the magnetoelectric effects have been found in the past several years. From a practical point of view, however, their magnetoelectric effects are useless because they operate only far below room temperature (for example, 28 K in TbMnO(3) (ref. 2) and 230 K in CuO (ref. 11)). Furthermore, in most of them, the operating magnetic field is an order of tesla that is too high for practical applications. Here we report materials, Z-type hexaferrites, overcoming these problems on magnetically induced ferroelectrics. The best magnetoelectric properties were obtained for Sr(3)Co(2)Fe(24)O(41) ceramics sintered in oxygen, which exhibit a low-field magnetoelectric effect at room temperature. Our result represents an important step towards practical device applications using the magnetoelectric effects.

Appropriate Color Enhancement Settings for Blue Laser Imaging Facilitates the Diagnosis of Early Gastric Cancer with High Color Contrast.

PURPOSE: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. MATERIALS AND METHODS: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. RESULTS: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. CONCLUSIONS: Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.

Late gadolinium-enhanced cardiovascular MRI at end-systole: feasibility study.

OBJECTIVE: The purpose of this article is to evaluate the image quality and infarct size of segmented late gadolinium-enhanced cardiovascular MRI at end-systole, compared with middiastole, in patients with sinus rhythm (SR) and to compare the image quality of end-systole images in patients with atrial fibrillation (AFib) to that of end-systole and middiastole images in patients with SR. SUBJECTS AND METHODS: Study patients (n = 121) were distributed according to heart rate and rhythm: SR with low heart rate (≤ 65 beats/minute), SR with intermediate heart rate (66-75 beats/minute), SR with high heart rate (≥ 76 beats/minute), and AFib. Image quality was graded on a 5-point scale, where 4 equals optimal and 0 equals not assessable. Global infarct size (percentage of left ventricle [LV] myocardium) in patients with SR with myocardial infarction was quantified using a visual quantitative approach with a 5-point scale and a semiautomatic method. RESULTS: End-systole imaging had higher image quality than did middiastole imaging for patients with SR with high heart rate, whereas middiastole imaging had higher image quality than did end-systole imaging for patients with SR with low heart rate (p < 0.05 for patients with SR with low heart rate, p = 0.60 for patients with SR with intermediate heart rate, and p = 0.001 for patients with SR with high heart rate). The quality of end-systole imaging in patients with AFib was not significantly different from that in patients with SR (p = 0.40 vs SR middiastole imaging and p = 0.38 vs SR end-systole imaging). The average difference of global infarct size was -0.3% and 0.2% of LV myocardium, and the limits of agreement were ± 2.4% and ± 3.3% of LV myocardium, for visual assessment and semiautomatic assessment, respectively. CONCLUSION: End-systole imaging can provide accurate diagnosis of myocardial infarction, comparable to middiastole imaging. The image quality of end-systole imaging is less susceptible to heart rate and rhythm compared with middiastole imaging.

Recurrent intestinal inflammation with a perianal abscess is not always Crohn's disease: a patient with a complex Meckel's diverticulum diagnosed by double-balloon endoscopy.

Recurrent intestinal inflammation and refractory perianal abscesses are typical manifestations of Crohn's disease. However, these conditions are not always due to Crohn's disease. A 25-year-old male with recurrent perianal abscesses for 1 year, suspected to be due to Crohn's disease, was referred for further evaluation. Computed tomography scan showed a perianal abscess abutting the small intestine. A complicated Meckel's diverticulum was suspected based on these findings. Meckel's diverticulum scintigraphy was negative. Bidirectional double-balloon endoscopy (DBE) identified a long diverticulum in the ileum. In this long diverticulum, a tight stricture was seen 5 cm distal to the diverticular opening. A selective contrast study showed a 10 cm diverticulum distal to the stricture, with three strictures in the long diverticulum. Inflammation of the Meckel's diverticulum due to bacterial overgrowth was suspected as a cause of the refractory perianal abscesses. Laparoscopic diverticulectomy was performed, and the specimen showed a 10 cm diverticulum containing post-inflammatory changes with scar formation. The perianal abscess was confirmed to be caused by an inflamed Meckel's diverticulum. The patient has been asymptomatic for 6 years after resection. DBE before exploratory laparotomy should be considered to investigate the cause of an abscess that could be secondary to small intestinal pathology.

ECG-edited middiastolic phase reconstruction improves image quality at 64-MDCT coronary angiography of patients with atrial fibrillation.

OBJECTIVE: The aims of this study were to evaluate image quality at the absolute middiastolic and absolute end-systolic phases of 64-MDCT coronary angiography of patients with atrial fibrillation and to compare the findings with those among patients in sinus rhythm. SUBJECTS AND METHODS: Nineteen consecutively registered patients with atrial fibrillation and 19 patients in sinus rhythm taking heart-rate-lowering agents as needed underwent MDCT. Images were reconstructed with a half-scan reconstruction algorithm after ECG editing (deletion of short R-R intervals, insertion of additional temporal windows into the middiastolic phase of long R-R intervals, and shift of R points). We used a 5-point scale (4, no motion artifacts; 0, unevaluable) to evaluate motion artifacts and coronary artery image discontinuities greater than 1 mm on the curved multiplanar reconstruction images. Each coronary artery image with a motion score of 2 or greater for all segments and with 2 or fewer discontinuities was considered acceptable for diagnosis. RESULTS: Middiastolic images of patients with atrial fibrillation showed fewer motion artifacts and image discontinuities than did end-systolic images of patients with atrial fibrillation. Despite greater heart rate variability under the condition of similar mean heart rates in patients with atrial fibrillation, motion artifacts and image discontinuities on middiastolic images were not significantly different from those on sinus rhythm images. Acceptable quality was achieved on 91% of middiastolic atrial fibrillation images and 93% of sinus rhythm images. CONCLUSION: ECG-edited middiastolic atrial fibrillation images with aggressive heart rate control were of better quality than end-systolic images in patients with atrial fibrillation. The diagnostic image quality of the middiastolic images was comparable with that of sinus rhythm images.

An in vivo model of autoimmune post-coxsackievirus B3 myocarditis in severe combined immunodeficiency mouse.

OBJECTIVE: Severe combined immunodeficiency (SCID) mice possess neither T nor B lymphocytes and are thus suitable recipients for adoptively transferred lymphocytes. Because autoimmune mechanisms may be involved in the pathogenesis of coxsackievirus B3 (CB3) myocarditis, we attempted to assess the in vitro cellular damage caused by antigen-sensitized lymphocytes and to determine whether splenic lymphocytes from BALB/c mice with chronic CB3 myocarditis could cause myocarditis into SCID mice. METHODS AND RESULTS: Cytotoxic cellular damage against non-myocytes and myocytes was demonstrated using 51Cr-release assay by lymphocytes cultured from myocarditis specimens or splenocytes from mice with chronic CB3 myocarditis. Severe T lymphocyte infiltration with myocardial necrosis was found in adoptively splenocyte-transferred SCID mice, but myocardial necrosis was not defected in wild-type mice by the same procedure. CONCLUSIONS: Autoimmune mechanisms might operate in mice with post-CB3 myocarditis and could be transferred in to SCID mice by the antigen-sensitized lymphocytes. An in vivo model of autoimmune post-viral myocarditis in SCID mouse was demonstrated.

Oral L-arginine prevents murine coxsackievirus B3 myocarditis.

We have previously demonstrated that administration of nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), aggravated murine coxsackievirus B3 myocarditis. In the present study, we evaluated the effects of L-arginine, a precursor of NO, upon acute and chronic myocarditis. Dietary L-arginine and L-arginine plus L-NAME (L-arginine+L-NAME group) were administered to coxsackievirus B3 (CB3)-infected C(3)H/He mice for 2 weeks (experiment I), and to CB3-infected mice from the second week until the fourth week after virus inoculation (experiment II). Infected control was prepared in each experiment. In experiment I, survival was higher in the L-arginine group compared with the other two groups, and cardiac damage was less. In addition, plasma concentrations of L-arginine and NO were elevated in the L-arginine group. In experiment II, cardiomyopathic lesion in the L-arginine group was less prominent associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. Thus, L-arginine treatment may be effective not only in preventing the development of acute CB3 myocarditis but in ameliorating cardiac dysfunction in chronic myocarditis.

Amyocarditic coxsackievirus B3 causes myocarditis in immunocompromised mice.

In the present study, we investigated the role of the immune status of the host in the pathogenesis and development of coxsackievirus B3 myocarditis. We compared the disease expression in myocarditic coxsackievirus B3 (CB3M)-infected BALB/c wild-type mice and severe combined immunodeficient (SCID) mice and in amyocarditic coxsackievirus B3 (CB3O)-infected BALB/c wild-type mice untreated or treated with immunosuppressive agents and SCID mice. There were no differences in viral growth in vitro between CB3M and CB3O. Severe myocarditis developed in CB3M-infected wild-type and SCID mice, CB3O-infected SCID mice and CB3O-infected wild-type mice with total immunosuppression. However, myocarditis was not induced in CB3O-infected wild-type mice untreated and treated with partial immunosuppression. There were no changes in myocardial virus titres among these groups of mice. In addition, myocarditis was induced in CB3O-infected wild-type mice treated with Thy 1.2 (pan T) or Lyt 2 (CD8) antibody but not in those mice treated with L3T4 (CD4) antibody. Thus, the CB3O variant did not induce myocarditis in wild-type mice associated with the induction of the CD8(+) lymphocyte subset but was shown to have the genetic capability to induce myocarditis if the host was in an almost total immunosuppressive or CD8-depleted state. The results suggest that induction of myocarditis by the amyocarditic strain of coxsackievirus B3 may occur and partially depends on the immune status of the host, and that myocarditis is due in part to an immunopathogenic mechanism.

Peri-infarct zone on early contrast-enhanced CMR imaging in patients with acute myocardial infarction.

OBJECTIVES: The aims of this study were to evaluate hyperenhanced regions on contrast-enhanced cardiovascular magnetic resonance (CE-CMR) imaging in patients with acute myocardial infarction (AMI) between early contrast-enhanced cardiovascular magnetic resonance (ECE) (2 min) and late contrast-enhanced cardiovascular magnetic resonance (LCE) (10 to 15 min) after gadolinium administration, and to compare the CE-CMR images with area at risk (AAR) derived from T2-weighted (T2W) CMR. BACKGROUND: Although CE-CMR imaging can demarcate the infarcted myocardium, the value of hyperenhancement in AMI is still in dispute. The size of hyperenhanced regions may vary with time, and overestimation can be often observed with early acquisition. METHODS: Thirty-four patients with successfully reperfused AMI underwent CMR within 4 days after the event. Myocardial regions as percentage of left ventricular (LV) myocardium were quantified on CE and T2W images. Relative peri-infarct zone was calculated as the difference in hyperenhanced regions between ECE and LCE, normalized to the individual infarct size. RESULTS: Both ECE and LCE images revealed hyperenhancement in the territory of the infarct-related artery in all patients. The hyperenhanced region on ECE extended transmurally and was consistently larger than that on LCE (39 ± 12% vs. 27 ± 12% of LV myocardium, p<0.001). The relative peri-infarct zone was inversely correlated with the transmurality of infarction (r=-0.59, p<0.001) and the time from symptom to reperfusion (r=-0.46, p<0.01). The hyperenhanced region on ECE was correlated with the T2W CMR-derived AAR (r=0.86, p<0.001) with the average difference of -0.8% and the limits of agreement of ±11.9%. CONCLUSIONS: ECE depicts ischemically injured but salvaged myocardium, as well as infarcted myocardium in patients with AMI. The myocardium at risk and infarcted myocardium after reperfusion can be retrospectively assessed by the combination of ECE and LCE.

Comparative effects of amlodipine monotherapy and combination therapy with betaxolol on cardiac autonomic nervous activity and health-related quality of life in patients with poorly controlled hypertension.

BACKGROUND: The aim of the study was to evaluate whether the combined treatment of calcium channel blocker, amlodipine and beta-blocker, betaxolol, favorably affects cardiac autonomic nervous activity (CANA) and health-related quality of life (HRQL). METHODS AND RESULTS: A total of 65 patients with a poor blood pressure (BP) control with a low dose amlodipine therapy were randomly assigned to the amlodipine dose-up group (n=21) and betaxolol adding group (n=44). Before and after a 6-month treatment, BP, heart rate variability (HRV), HRQL and blood chemistries were evaluated. Low frequency (LF) spectra/high frequency (HF) spectra and HF/total power spectra (TP) were calculated as indexes of CANA, and HRQL was assessed by the questionnaire sheets. BP was well controlled in all patients of the present study. In the betaxolol adding group, LF/HF decreased (2.1+/-1.9 to 1.3+/-0.9, p<0.05) and HF/TP reciprocally increased (0.41+/-0.17 to 0.52+/-0.18, p<0.05), whereas the amlodipine dose-up group showed no significant changes in the HRV. HRQL was significantly improved in the betaxolol adding group, whereas it remained unchanged in the amlodipine dose-up group. Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group (36+/-47 to 62+/-62 pg/ml, p<0.05). CONCLUSIONS: Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy, because combined treatment improves CANA and HRQL.

Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction.

We previously reported that continuous intravenous (IV) administration of nicorandil (NIC) inhibits QT dispersion (QTd). However, no prior study has evaluated the efficacy of NIC when administered orally to acute myocardial infarction (AMI) patients following continuous IV administration. Thirty patients with anteroseptal infarction in whom revascularization was performed successfully within 6 hours of AMI onset were included in the study and assigned to one of 3 groups: group A (continuous IV administration of NIC), group B (continuous IV and oral administration of NIC), and group C (no treatment with NIC). After 24 hours, QTd in groups A and B was significantly decreased compared to QTd in group C (P < 0.01) (group A, 58.1; group B, 58.2; and group C, 81.3). The QTd obtained 3 months later was significantly shorter in group B subjects who were orally administered NIC, and QTd before percutaneous coronary intervention (PCI) was restored in group A, in which no NIC had been administered orally [group A, 66.7; group B, 54.1; and group C, 73.9; P < 0.05 (group A versus group B) and P < 0.01 (group B versus group C)]. The effects were evaluated by comparing different routes of administration. Continuous IV and subsequent oral administration of NIC inhibited prolongation of QTd, suggesting that these effects may prevent the occurrence of cardiac events during both the acute and chronic phases of AMI.

[Effects of immunoglobulin on murine myocarditis caused by influenza A virus: experimental study].

OBJECTIVES: Influenza A viruses play the largest role in the worldwide epidemiology of infectious diseases. We examined the effects of intact type and F(ab')2 type of immunoglobulin preparations on murine influenza A virus myocarditis in mice. METHODS AND RESULTS: In vitro study showed that intact type and F(ab')2 type of immunoglobulin preparations had antiviral activities against many substrains of influenza A virus and other cardiotropic viruses, and that dose-dependent suppression of an influenza A virus (NWS type) was demonstrated by the treatment of both intact immunoglobulin and F(ab')2 fragments of immunoglobulin. The dose inhibiting 50% of plaques was same between intact type and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2 fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2 (MIP-2) production in influenza A virus infected macrophages in vitro, which is a murine counterpart of interleukin-8. This suppression of MIP-2 production by intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma III/II receptor) antibody pretreatment. Intact immunoglobulin (1 g/kg/day) or F(ab')2 fragments of immunoglobulin (1 g/kg/day) were administered to the virus-inoculated A/J mice intraperitoneally daily, starting simultaneously with virus inoculation (Experiment I ) and 2 days after the virus inoculation (Experiment II ), until 10th days after virus inoculation. In Experiment I, survival was higher in treated [intact (100%, 20/20), and F(ab')2 (100%, 20/20)] than in control (25%, 5/20) mice; intact type and F(ab')2 type immunoglobulin administration completely suppressed the development of myocarditis. In Experiment II, survival rate was significantly higher (75%, 15/20) and myocarditis was less severe in intact immunoglobulin treated mice, but not in F(ab')2 fragment treated mice (60%, 12/20), than in untreated mice (35%, 7/20). Serum neutralizing antibody titers in treated mice were significantly higher compared with untreated mice in Experiments I and II. In addition, serum MIP-2 concentrations in intact immunoglobulin treated mice, but not in F(ab')2 fragments treated mice, were lower compared with untreated mice in Experiment II. Immunoglobulin therapy suppresses influenza A virus myocarditis by increasing neutralizing antibody titers and the suppression of myocardial virus activities. From the stand-point of suppression of MIP-2 concentrations, intact type is superior to F(ab')2 type. CONCLUSIONS: Immunoglobulin treatment may be promising for the prevention of influenza A virus myocarditis.

Effects of immunoglobulin upon murine myocarditis caused by influenza A virus: superiority of intact type to F(ab')2 type.

Influenza viruses play the largest role in the worldwide epidemiology of infectious diseases. Management of some inflammatory disease (eg, Kawasaki disease) with immunoglobulin has been demonstrated to be effective. We examined the effects of intact type and F(ab')2 type of immunoglobulin preparations upon murine influenza A virus myocarditis in mice. In vitro study showed that intact type and F(ab')2 type of immunoglobulin preparations exhibit antiviral activities against many substrains of influenza virus and other cardiotropic viruses. Dose-dependent suppression of an influenza A virus (NWS) was demonstrated by management with both intact immunoglobulin and F(ab')2 fragments of immunoglobulin. The dose inhibiting 50% of plaques was the same between intact type and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2 fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2 (MIP-2) productions in influenza A virus-infected macrophages in vitro, which is a murine counterpart of interleukin-8. This suppression of MIP-2 production by intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma III/II receptor) antibody pretreatment. Intact immunoglobulin or F(ab')2 fragments of immunoglobulin were administered to virus-inoculated A/J mice intraperitoneally daily, starting simultaneously with virus inoculation (Experiment I) and 2 days after the virus inoculation (Experiment II), until 10 days after virus inoculation. In Experiment I, survival was higher in treated than in control mice; intact type and F(ab')2 type immunoglobulins administration completely suppressed the development of myocarditis. In Experiment II, survival rate was significantly higher and myocarditis was less severe in intact immunoglobulin-treated mice, but not in F(ab')2 fragments-treated mice compared with untreated mice. Serum neutralizing antibody titers in treated mice were significantly higher compared with untreated mice in Experiments I and II. In addition, serum MIP-2 concentrations in intact immunoglobulin-treated mice, but not in F(ab')2 fragments-treated mice, were lower compared with untreated mice in Experiment II. Immunoglobulin therapy suppresses influenza A virus myocarditis by increasing neutralizing antibody titers and the suppression of myocardial virus activities. From the standpoint of suppression of MIP-2 concentrations, intact type is superior to F(ab')2 type. Thus, immunoglobulin treatment may be promising for prevention of influenza virus myocarditis.

Oral administration of L-arginine prevents congestive heart failure in murine viral myocarditis.

It was previously demonstrated that administration of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) aggravated viral myocarditis in mice. In the current study, the effects of l-arginine, a precursor of nitric oxide, on congestive heart failure (CHF) in myocarditis were evaluated. Dietary l-arginine and l-arginine plus l-NAME (l-arginine + l-NAME group) were administered to encephalomyocarditis virus-infected BALB/c mice over 4 weeks (experiment I) and to encephalomyocarditis virus-infected DBA/2 mice from the 4th through 12th weeks after the virus inoculation (experiment II). An infected control was prepared in each experiment. In experiment I, survival was higher in the l-arginine group compared with the other two groups, and cardiac damage was less, as was incidence of CHF. In addition, extravasated fibrin was less prominent in the l-arginine group. Plasma concentrations of l-arginine and nitric oxide were elevated in the l-arginine group. In experiment II, plasma cardiomyopathic lesions in the l-arginine group were less prominent and were associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. l-arginine treatment may be effective in preventing the development of CHF in viral myocarditis by modifying postmyocarditic architectural remodeling.