Ex Vivo Assessment of Contractility,Fatigability and Alternans in Isolated Skeletal Muscles

Described here is a method to measure contractility of isolated skeletal muscles. Parameters such as muscle force, muscle power, contractile kinetics, fatigability, and recovery after fatigue can be obtained to assess specific aspects of the excitation-contraction coupling (ECC) process such as excitability, contractile machinery and Ca²⁺ handling ability. This method removes the nerve and blood supply and focuses on the isolated skeletal muscle itself. We routinely use this method to identify genetic components that alter the contractile property of skeletal muscle though modulating Ca²⁺ signaling pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e., mechanic alternans, as an example of the various and rich information that can be obtained using the in vitro muscle contractility assay. Combination of this assay with single cell assays, genetic approaches and biochemistry assays can provide important insights into the mechanisms of ECC in skeletal muscle.     

利用Poincare 散点图法检测t 波交替的指标研究

目的:利用Poincare散点图进行t波交替检测,不仅从形态上找到检测标准,进一步研究散点中有效的定量指标。方法:以European ST-T Database标准心电数据库和MIT-BIH心律失常数据库的心电信号作为检测对象,以128个连续心拍的t波中的7个点为检测数据,相邻心拍t波差分后组成新序列,并由差分序列作出散点图,观察散点形态。根据形态区别和t波交替的幅值变化特点,利用个散点到x+y=0直线的距离均值作为定量检测指标D0,为避免不同心电信号幅值影响,D0除以RQ峰值差为最终指标D,找出合适阈值判定是否存在t波交替,并与谱分析法的检测结果比较分析。结果:①从Poincare散点图形态上,存在t波交替的散点图与正常t波存在明显区别,存在t波交替则散点集中在以x+y=0为轴线的附近,形成类似椭圆的狭长形状;而正常t波形成的散点会以原点为中心均匀分布,散点形态为圆形。②由t波交替的特点和散点图形态可知,定量检测指标D越小,就越有可能存在t波交替。经过大量仿真测试和谱分析法的比较,规定检测标准为,当D<=35uv时,存在t波交替;指标D与谱分析法的结论相吻合,并且两种方法的判定结果由kappa一致性检验,一致性程度好,进一步说明D指标具有优越的敏感性,是t波交替检测的有效指标。结论:Poincare散点图的散点分布形态和散点到x+y=0轴线的距离均值分别是是t波交替有效的定性和定量检测指标。     

微伏T波电交替对STEMI患者PCI术后室性心律失常的预测价值*

摘要目的：探讨微伏T 波电交替增高与STEMI患者PCI术后室性心律失常的发生关系。方法：选择我院2011 年4 月～2013 年 4月收治的68 例STEMI患者,所有患者均成功进行了直接PCI,且阻塞远端血流均达到TIMI 3级。所有患者于手术后进行了24 小时动态心电图检查,并测定微伏T 波电交替值。结果：36 例发生NSVT患者较未发生32 例患者最大微伏T 波电交替明显升 高,（68.1± 6.4 vs 31.9± 3.8 μV, P< 0.05)。最大T 波电交替值大于45 μV 预测非持续性室速发生的敏感性为75%,特异性为72%; 阳性预测值为70%,阴性预测值77%(AUC = 0.84)。经过进一步比较分析发现,ST 段抬高的程度与非持续室速的发生无关(AUC =0.61)。结论：微伏T 波电交替可预测STEMI患者PCI术后室性心律失常的发生。     

Alterations in the rat electrocardiogram induced by stationary magnetic fields

A field strength dependent increase in the amplitude of the T-wave signal in the rat electrocardiogram (ECG) was observed during exposure to homogeneous, stationary magnetic fields. For 24 adult Sprague-Dawley and Buffalo rats of both sexes, the T-wave amplitude was found to increase by an average of 408% in a 2.0 Tesla (1 Tesla = 10⁴ Gauss) field. No significant magnetically induced changes were observed in other components of the ECG record, including the P wave and the QRS complex. The minimum field level at which augmentation of the T wave could be detected was 0.3 Tesla. The magnetically induced increase in T-wave amplitude occurred instantaneously, and was immediately reversible after exposure to fields as high as 2.0 Tesla. No abnormalities in any component of the ECG record, including the T wave, were noted during a period of 3 weeks following cessation of a continuous 5-h exposure of rats to a 1.5-Tesla field. The heart rate and breathing rate of adult rats were not altered during, or subsequent to, application of fields up to 2.0 Tesla. The effect of animal orientation within the field was tested using juvenile rats 3–14 days old. The maximum increase in T-wave amplitude was observed when subjects were placed with the long axis of the body perpendicular to the lines of magnetic induction. These experimental observations, as well as theoretical considerations, suggest that augmentation of the signal amplitude in the T-wave segment of the ECG may result from a superimposed electrical potential generated by aortic blood flow in the presence of a stationary magnetic field.     

Feedback-control induced pattern formation in cardiac myocytes: A mathematical modeling study

Cardiac alternans is a dangerous rhythm disturbance of the heart, in which rapid stimulation elicits a beat-to-beat alternation in the action potential duration (APD) and calcium (Ca) transient amplitude of individual myocytes. Recently, “subcellular alternans”, in which the Ca transients of adjacent regions within individual myocytes alternate out-of-phase, has been observed. A previous theoretical study suggested that subcellular alternans may result during static pacing from a Turing-type symmetry breaking instability, but this was only predicted in a subset of cardiac myocytes (with negative Ca to voltage (Ca→V_m) coupling) and has never been directly verified experimentally. A recent experimental study, however, showed that subcellular alternans is dynamically induced in the remaining subset of myocytes during pacing with a simple feedback control algorithm (“alternans control”). Here we show that alternans control pacing changes the effective coupling between the APD and the Ca transient (V_m→Ca coupling), such that subcellular alternans is predicted to occur by a Turing instability in cells with positive Ca→V_m coupling. In addition to strengthening the understanding of the proposed mechanism for subcellular alternans formation, this work (in concert with previous theoretical and experimental results) illuminates subcellular alternans as a striking example of a biological Turing instability in which the diffusing morphogens can be clearly identified.     

Quantitative characterization of repolarization alternans in terms of amplitude and location: What information from different methods?

The qualitative definition of repolarization alternans (RA) as an every-other-beat alternation of the repolarization amplitude allows several possible quantitative characterizations of RA. In the absence of a standardization, any correct comparison among quantitative outputs by different automatic methods requires knowledge of the differences in the RA parameterization at the basis of their algorithms. Thus, aim of the present study was to investigate the kind of information provided by five methods, namely the fast Fourier spectral method (FFTSM), the complex demodulation method (CDM), the modified moving average method (MMAM), the Laplacian likelihood ratio method (LLRM) and the heart-rate adaptive match filter method (AMFM) when characterizing RA in terms of its amplitude and location. Eight synthetic ECG recordings affected by stationary RA with uniform and triangular profiles localized along the ST segment, over the T wave, at the end of the T wave and all along the JT segment, respectively, were considered. Results indicate that quantitative RA characterization is method dependent. More specifically, the FFTSM and the LLRM provide a measure that matches the root mean square of the RA profile over the JT segment. Instead, the CDM and the AMFM compute RA amplitude as the mean value of the RA profile over the JT segment. Eventually, the MMAM provides the maximum amplitude difference between consecutive beats along repolarization. RA location is homogeneously among methods, since they all provide the time instant in correspondence of which the center of mass of the alternation occurs.     

QRS alternans during right ventricular pacing while ablating a concealed left sided accessory pathway

A 16-year-old boy was referred for an electrophysiological study for documented regular narrow complex tachycardia. A diagnosis of a concealed left lateral accessory pathway was made with an eccentric atrial activation sequence both during tachycardia and right ventricular (RV) pacing. The pathway was mapped at the left posterior mitral vestibule during RV pacing, performed through the distal tip of the His bundle catheter pushed into right ventricular outflow tract. An unusual response to ventricular stimulation with alternation of QRS complex width and morphology was noted. The possible mechanisms are hereby discussed.