Background-Mutations in the cardiac Na ϩ channel gene (SCN5A) can adversely affect electric function in the heart, but effects can be age dependent. We explored the interacting effects of Scn5a disruption and aging on the pathogenesis of sinus node dysfunction in a heterozygous Scn5a knockout (Scn5a ϩ/Ϫ ) mouse model. Methods and Results-We compared functional, histological, and molecular features in young (3 to 4 month) and old (1 year) wild type and Scn5a ϩ/Ϫ mice. Both Scn5a disruption and aging were associated with decreased heart rate variability, reduced sinoatrial node automaticity, and slowed sinoatrial conduction. They also led to increased collagen and fibroblast levels and upregulated transforming growth factor-␤ 1 (TGF-␤ 1 ) and vimentin transcripts, providing measures of fibrosis and reduced Nav1.5 expression. All these effects were most noticeable in old Scn5a ϩ/Ϫ mice. Na ϩ channel inhibition by Nav1.5-E3 antibody directly increased TGF-␤ 1 production in both cultured human cardiac myocytes and fibroblasts. Finally, aging was associated with downregulation of a wide range of ion channel and related transcripts and, again, was greatest in old Scn5a ϩ/Ϫ mice. The quantitative results from these studies permitted computer simulations that successfully replicated the observed sinoatrial node phenotypes shown by the different experimental groups. Conclusions-These results implicate a tissue degeneration triggered by Nav1.5 deficiency manifesting as a TGF-␤ 1 -mediated fibrosis accompanied by electric remodeling in the sinus node dysfunction associated with Scn5a disruption or aging. The latter effects interact to produce the most severe phenotype in old Scn5a ϩ/Ϫ mice. In demonstrating this, our findings suggest a novel regulatory role for Nav1.5 in cellular biological processes in addition to its electrophysiologic function. (Circ Arrhythm Electrophysiol. 2011;4:397-406.) Key Words: sinoatrial node Ⅲ aging Ⅲ remodeling Ⅲ ion channels Ⅲ Nav1.5 protein S inus node dysfunction (SND) is associated with abnormal impulse formation and propagation in the sinoatrial node (SAN). It presents clinically as sinus bradycardia, sinus pause or arrest, atrial chronotropic incompetence, and SAN exit block. 1 It affects Ϸ1 in 600 cardiac patients aged Ͼ65 years and is responsible for Ϸ50% of the 1 million permanent pacemaker implants per year worldwide. 2,3 Although SND occurs most commonly in elderly patients in the absence of clinically apparent accompanying cardiac disease, 2 its pathogenesis is unclear. Nevertheless, experimental animal models do show structural, electrophysiological, and ion channel remodeling with age. 2,4 -7 Furthermore, genetic defects in ion channels that include those involving human Nav1.5 have been associated with familial sick sinus syndrome, a rare congenital form of SND. 8 -10 Finally, genetic defects in SCN5A also are associated with progressive (ie, agedependent) cardiac conduction disease (PCCD), which often is accompanied by SND. 10,11 Clinical Perspective on p 406The clinical s...

The present study provides new insights into the dermoscopic variability of DLE located on the face, trunk and extremities.

BackgroundReduction in visual acuity combined with blurred vision is rarely the first sign of lung cancer and very few cases have been announced globally.Case presentationA case of a 46-year-old man who admitted with blurred vision is presented. His medical history, apart from a mild gastritis under treatment was negative. Ocular examination revealed a decrease in visual acuity due to a choroidal tumor. Further image body scans demonstrated a right lung lesion with dissemination to other organs. Diagnosis of a non-small cell lung cancer established after a VATS biopsy carried out.ConclusionBlurred vision due to choroidal metastasis as the primary symptom of lung cancer is very uncommon. A great index of suspicion is essential when a choroidal lesion appears.

Mediastinum is a common site where benign tumors, like teratomas, can develop. Usually, these lesions do not cause any symptoms and the diagnosis is reached accidentally. As they enlarge they may cause symptoms by compressing the nearby structures of the thorax, mostly the trachea and the bronchi. Extrinsic compression of the heart or the great vessels appears to be a very rare occurrence. Atrial fibrillation as the first clinical presentation of left atrial compression by a giant mediastinal teratoma is extremely uncommon and very few cases have been described in the English literature.

BackgroundLeiomyomas of esophagus, although rare, are the most frequent benign tumors of esophagus. Aim of this study is the presentation of 7 patients with esophageal leiomyomas who underwent surgical treatment during a 9-year period.MethodsEpidemiological data (sex, age), the presenting symptoms, diagnostic examinations, tumor location, histopathological findings and the safety and efficacy of surgical resection are analyzed and assessed.Results5 men and 2 women with mean age of 56.9 years were operated. In 3 cases the tumor was located at the lower esophagus, while in the other 4 cases, the leiomyoma was found at the median third of esophagus. 4 patients had severe symptoms related to the leiomyoma, such as dysphagia and epigastric pain. All patients underwent a right postolateral thoracotomy with enucleation of the lesion. None of them received resection of part of the esophagus. The mean diameter of the resected tumors was 4.3 cm. The dimensions of leiomyomas were immediately associated with the symptoms. In no case was detected malignancy or recurrence. All patients were relieved from their symptoms, while postoperative morbidity and mortality did not occur.ConclusionsEsophageal leiomyoma is a benign tumor, which causes symptoms only if its size becomes large. Surgical enucleation is considered to be safe and effective, without complications.

Digoxin is one of the oldest compounds used in cardiovascular medicine. Nevertheless, its mechanism of action and most importantly its clinical utility have been the subject of an endless dispute. Positive inotropic and neurohormonal modulation properties are attributed to digoxin, and it was the mainstay of heart failure therapeutics for decades. However, since the institution of β-blockers and aldosterone antagonists as part of modern heart failure medical therapy, digoxin prescription rates have been in free fall. The fact that digoxin is still listed as a valid therapeutic option in both American and European heart failure guidelines has not altered clinicians' attitude towards the drug. Since the publication of original Digitalis Investigation Group trial data, a series of reports based predominately on observational studies and post hoc analyses have raised concerns about the clinical efficacy and long-term safety of digoxin. In the present review, we will attempt a critical appraisal of the available clinical evidence regarding the efficacy and safety of digoxin in heart failure patients with a reduced ejection fraction. The methodological issues, strengths, and limitations of individual studies will be highlighted.

No abstract

Minimal invasive extracorporeal circulation (MiECC) has initiated important new efforts within science and technology towards a more physiologic perfusion. In this study, we aim to investigate the learning curve of our center regarding MiECC. We studied a series of 150 consecutive patients who underwent elective coronary artery bypass grafting by the same surgical team during the initial phase of MiECC application. Patients were randomly assigned into two groups. Group A (n = 75) included patients operated on MiECC, while group B (n = 75) included patients operated with conventional cardiopulmonary bypass (cCPB). The primary end-point of the study was to identify whether there is a learning curve when operating on MiECC. The following parameters were unrelated with increasing experience, even though the results favored MiECC use: reduced CPB duration (102.9 ± 25 vs. 122.2 ± 33 min, P <0.001), peak troponin release (0.07 ± 0.02 vs. 0.1 ± 0.04 ng/mL, P < 0.01), peak creatinine levels (0.97 ± 0.24 vs. 1.2 ± 0.3 mg/dL, P < 0.001), duration of mechanical ventilation (14.1 ± 7.2 vs. 36.9 ± 59.8 h, P < 0.01) and ICU stay (2.1 ± 0.7 vs. 4.4 ± 6.4 days, P < 0.01). However, need for intraoperative blood transfusion showed a trend towards a gradual decrease as experience with MiECC system was accumulating (R = 0.094, P = 0.007). Subsequently, operational learning applied to postoperative hematocrit and hemoglobin levels (R = 0.098, P = 0.006). We identified that advantages of MiECC technology in terms of reduced hemodilution and improved end-organ protection and clinical outcome are evident from the first patient. Optimal results are obtained with 50 cases; this refers mainly to significant reduction in the need for intraoperative blood transfusion. Teamwork from surgeons, anesthesiologists, and perfusionists is of paramount importance in order to maximize the clinical benefits from this technology.