Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy.

Numerous studies have implicated Coxsackievirus in acute and chronic heart failure. Although enteroviral nucleic acids have been detected in selected patients with dilated cardiomyopathy, the significance of such persistent nucleic acids is unknown. To investigate the mechanisms by which restricted viral replication with low level expression of Coxsackieviral proteins may be able to induce cardiomyopathy, we generated transgenic mice which express a replication-restricted full-length Coxsackievirus B3 (CVB3) cDNA mutant (CVB3DeltaVP0) in the heart driven by the cardiac myocyte-specific myosin light chain-2v (MLC-2v) promoter. CVB3DeltaVP0 was generated by mutating infectious CVB3 cDNA at the VP4/VP2 autocatalytic cleavage site from Asn-Ser to Lys-Ala. Cardiac-specific expression of this cDNA leads to synthesis of positive- and negative-strand viral RNA in the heart without formation of infectious viral progeny. Histopathologic analysis of transgenic hearts revealed typical morphologic features of myocardial interstitial fibrosis and in some cases degeneration of myocytes, thus resembling dilated cardiomyopathy in humans. There was also an increase in ventricular atrial natriuretic factor mRNA levels, demonstrating activation of the embryonic program of gene expression typical of ventricular hypertrophy and failure. Echocardiographic analysis demonstrated the presence of left ventricular dilation and decreased systolic function in the transgenic mice compared with wild-type littermates, evidenced by increased ventricular end-diastolic and end-systolic dimensions and decreased fractional shortening. Analysis of isolated myocytes from transgenic mice demonstrate that there is defective excitation-contraction coupling and a decrease in the magnitude of isolated cell shortening. These data demonstrate that restricted replication of enteroviral genomes in the heart can induce dilated cardiomyopathy with excitation-contraction coupling abnormalities similar to pressure overload models of dilated cardiomyopathy.     

Focal myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in children and adolescents with dilated cardiomyopathy

Background

Different patterns of late gadolinium enhancement (LGE) including mid-wall fibrosis using cardiovascular magnetic resonance (CMR) have been reported in adult patients presenting with non-ischemic dilated cardiomyopathy (DCM). In these studies, LGE was associated with pronounced LV remodelling and predicted adverse cardiac outcomes. Accordingly, the purpose of our study was to determine the presence and patterns of LGE in children and adolescents with DCM.

Methods

Patients <18 years of age presenting with severe congestive heart failure who were admitted for evaluation of heart transplantation at our centre underwent CMR examination which consisted of ventricular functional analysis and assessment of LGE for detection of myocardial fibrosis. Ischemic DCM was excluded by coronary angiography, and right ventricular endomyocardial biopsies ruled out acute myocarditis.

Results

Thirty-one patients (mean age 2.1 ± 4.2 years) with severe LV dilatation (mean indexed LVEDV 136 ± 48 ml/m²) and LV dysfunction (mean LV-EF 23 ± 8%) were examined. LGE was detected in 5 of the 31 patients (16%) appearing in various patterns characterized as mid-wall (n = 1), focal patchy (n = 1), RV insertion site (n = 1) and transmural (n = 2). Based on histopathological analysis, 4 of the 5 LGE positive patients had lymphocytic myocarditis, whereas one patient was diagnosed with idiopathic DCM.

Conclusions

In children and adolescents with DCM, focal histologically proven myocardial fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely depressed LV function. LGE occurred in various patterns and mostly in patients with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis in childhood DCM reflects different endogenous repair mechanisms that enable favourable reverse remodelling. Larger trials are needed to assess the prognostic implications of LGE in childhood DCM.     

Arrhythmogenic right ventricular dysplasia/cardiomyopathy - diagnosis in childhood

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare, but important cause for sudden death in adolescents and young adults. Part of the patients affected show the pattern of autosomal-dominant inheritance. Two pediatric patients with ARVD/C are presented who may reflect the spectrum of clinical presentation of ARVD/C in childhood resulting in difficulties or even delay to establish the correct diagnosis. One patient with a sporadic form of ARVD/C presented with a syncope and spontaneous as well as inducible ventricular tachycardia. On the ECG, an epsilon wave could be identified. An automatic cardioverter defibrillator was implanted. The second patient had a familiar form of ARVD/C with no symptoms. There was a history of frequent sudden deaths in this family. Biopsies of the right ventricular myocardium showed fibrosis with deposition of fatty tissue. There was clear evidence of ARVD/C in the necropsy of the patient's aunt. Therapy with propanolol was started in this patient.     

应用MIPO技术锁定钢板内固定治疗胫骨粉碎性骨折

目的：观察应用MIPO技术(微创钢板接骨术)锁定钢板内固定治疗胫骨粉碎性骨折的临床效果。方法：使用MIPO技术对20例胫骨干粉碎性骨折进行锁定钢板内固定。术后平均随访8个月。结果：20例骨折均复位良好、顺利愈合,功能恢复良好。结论：运用MIPO技术锁定钢板内固定治疗胫骨干粉碎性骨折具有较高的临床应用价值。     

负压封闭引流术治疗胫腓骨开放性骨折合并严重软组织损伤

目的：探讨应用负压封闭引流技术治疗胫腓骨开放性骨折合并严重软组织损伤的疗效。方法：对14例胫腓骨开放性骨折合并严重软组织损伤患者,进行清创及骨折固定后,应用持续负压封闭引流,6～8 d后拆除敷料。必要时再次行负压封闭引流,二期植皮。结果：14例患者中5例皮肤回植大部分成活,7例患者使用负压封闭引流术治疗后行二期植皮全部...