Sudden cardiac death in young children with neurofibromatosis type 1

Patients with neurofibromatosis type 1 (NF1) can manifest a characteristic vasculopathy that in adults is rarely associated with fatal coronary artery occlusion. We describe the clinical and pathological findings from 2 unrelated young children with NF1, a similar vasculopathy affecting their coronary arteries, and sudden cardiac death.     

New drugs vs. old concepts: a fresh look at antiarrhythmics

Common arrhythmias, particularly atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are a major public health concern. Classic antiarrhythmic (AA) drugs for AF are of limited effectiveness, and pose the risk of life-threatening VT/VF. For VT/VF, implantable cardiac defibrillators appear to be the unique, yet unsatisfactory, solution. Very few AA drugs have been successful in the last few decades, due to safety concerns or limited benefits in comparison to existing therapy. The Vaughan-Williams classification (one drug for one molecular target) appears too restrictive in light of current knowledge of molecular and cellular mechanisms. New AA drugs such as atrial-specific and/or multichannel blockers, upstream therapy and anti-remodeling drugs, are emerging. We focus on the cellular mechanisms related to abnormal Na⁺ and Ca²⁺ handling in AF, heart failure, and inherited arrhythmias, and on novel strategies aimed at normalizing ionic homeostasis. Drugs that prevent excessive Na⁺ entry (ranolazine) and aberrant diastolic Ca²⁺ release via the ryanodine receptor RyR2 (rycals, dantrolene, and flecainide) exhibit very interesting antiarrhythmic properties. These drugs act by normalizing, rather than blocking, channel activity. Ranolazine preferentially blocks abnormal persistent (vs. normal peak) Na⁺ currents, with minimal effects on normal channel function (cell excitability, and conduction). A similar “normalization” concept also applies to RyR2 stabilizers, which only prevent aberrant opening and diastolic Ca²⁺ leakage in diseased tissues, with no effect on normal function during systole. The different mechanisms of action of AA drugs may increase the therapeutic options available for the safe treatment of arrhythmias in a wide variety of pathophysiological situations.     

Challenges to normal neural functioning provide insights into separability of motion processing mechanisms

There is a long history of attempts to disentangle different visual processing mechanisms for physically different motion cues. However, underlying neural correlates and separability of networks are still under debate. We aimed to refine the current understanding by studying differential vulnerabilities when normal neural functioning is challenged. We investigated effects of ageing and extrastriate brain lesions on detection thresholds for motion defined by either luminance- or contrast modulations, known as first- and second-order motion. Both approaches focus on extrastriate processing changes and combine distributed as well as more focal constraints. Our ageing sample comprised 102 subjects covering an age range from 20 to 82 years. Threshold signal-to-noise ratios for detection approximately doubled across the age range for both motion types. Results suggest that ageing affects perception of both motion types to an equivalent degree and thus support overlapping processing resources. Underlying neural substrates were further qualified by testing perceptual performance of 18 patients with focal cortical brain lesions. We determined selective first-order motion deficits in three patients, selective second-order motion deficits in only one patient, and deficits for both motion types in three patients. Lesion analysis yielded support for common functional substrates in higher cortical regions. Functionally specific substrates remained ambiguous, but tended to cover earlier visual areas. We conclude that observed vulnerabilities of first- and second-order motion perception provide limited evidence for functional specialization at early extrastriate stages, but emphasize shared processing pathways at higher cortical levels.     

自动体外除颤器与人工除颤器对幼猪室颤模型的除颤效果☆

背景：目前对8岁以下儿童电除颤的有效剂量及安全范围尚无统一的规定。 目的：使用自动体外除颤器及人工除颤器与儿童用电极对幼猪室颤模型除颤,进行有效性及安全性评价。 设计、时间及地点：实验猪电除颤体外实验,于2006-10/2007-05在苏州大学实验动物中心动物手术室完成。 材料：2月龄太湖猪30只,体质量7.0~25.0 kg,由常熟畜禽良种有限公司提供。 方法：30只幼年太湖猪,按体质量随机分为自动体外除颤器组和人工除颤组,每组15只。诱发室颤2 min后分别以自动体外除颤器及人工除颤器50 J除颤,一次电击后立即进行心肺复苏,不复律的动物以70 J电击后联用心肺复苏。除颤后不同时间做血气分析、电解质及心肌酶谱检查、超声波心功能测定和神经学打分,72 h后处死作大体解剖。 主要观察指标：动态监测整个实验过程动物心电图、血压、呼吸、体温等,检查除颤前后动物的超声心动图、血气、电解质、神经行为学打分以及大体解剖。 结果：两组动物50 J一次电击后立即给与心肺复苏,复苏成功率达86.7%;部分猪放电除颤后心电图ST段压低或抬高,并在几分钟内回到基线;两组动物除颤成功后心脏射血分数、左心室面积变化分数3.0~4.0 h内均显著降低(P < 0.05),72 h恢复正常;血液分析各项指标与试验前差别无统计学意义(P > 0.05);复苏后神经行为和大体解剖未见异常。 结论：应用成人双相波自动体外除颤器联用具备能量衰减配件的儿童专用电极,对7~25 kg的幼猪室颤模型取得了较满意的复苏效果。     

Mapping of ventricular arrhythmias using a novel noninvasive epicardial and endocardial electrophysiology system

Introduction

The aim of this study was to assess the use of a novel noninvasive epicardial and endocardial electrophysiology system (NEEES) for mapping of ventricular arrhythmias.

Cardiorespiratory Fitness and the Risk of Serious Ventricular Arrhythmias: A Prospective Cohort Study

Cardiorespiratory fitness (CRF) is an established risk factor for cardiovascular disease outcomes. However, the relationship of CRF with risk of ventricular arrhythmias (VAs) is unknown. We aimed to assess the prospective association of CRF with the risk of serious VAs. Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed using a respiratory gas exchange analyzer in 2299 middle-aged men in the Kuopio Ischemic Heart Disease prospective cohort. We corrected for within-person variability in CRF levels using data from repeated measurements 11 years apart. During median follow-up of 25.3 years (interquartile range, 18.7-27.2 years), 73 serious VAs were recorded. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI, 0.53-0.64). In analysis adjusted for age, the hazard ratio (HR) for serious VAs per 1-SD increase in CRF was 0.64 (95% CI, 0.49-0.84). The association persisted on additional adjustment for body mass index, systolic blood pressure, history of hypertension, prevalent coronary heart disease, smoking, history of diabetes, cholesterol level, alcohol consumption, and physical activity (HR, 0.67; 95% CI, 0.51-0.88). The corresponding adjusted HRs (95% CIs) were 0.29 (0.14-0.59) and 0.32 (0.15-0.65), respectively, comparing the top vs bottom tertiles. The associations were stronger on correction for regression dilution bias, remained consistent on exclusion of men with a history of coronary heart disease, and did not vary importantly in several relevant clinical subgroups. Cardiorespiratory fitness is inversely associated with future risk of serious VAs, independently of several cardiovascular disease risk factors. Further research is needed to assess the causal relevance of these findings.