A 50% Reduction of Excitability but Not of Intercellular Coupling Affects Conduction Velocity Restitution and Activation Delay in the Mouse Heart

Computer simulations suggest that intercellular coupling is more robust than membrane excitability with regard to changes in and safety of conduction. Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by approximately 50%. In this retrospective study we assessed the effect of reduced membrane excitability or intercellular coupling on conduction in mouse models of reduced excitability or intercellular coupling. Epicardial activation mapping of LV and RV was performed on Langendorff-perfused mouse hearts having the following: 1) Reduced excitability: Scn5a haploinsufficient mice; and 2) reduced intercellular coupling: Cx43(CreER(T)/fl) mice, uninduced (50% Cx43) or induced (10% Cx43) with Tamoxifen. Wild type (WT) littermates were used as control. Conduction velocity (CV) restitution and activation delay were determined longitudinal and transversal to fiber direction during S(1)S(1) pacing and S(1)S(2) premature stimulation until the effective refractory period. In both animal models, CV restitution and activation delay in LV were not changed compared to WT. In contrast, CV restitution decreased and activation delay increased in RV during conduction longitudinal but not transverse to fiber direction in Scn5a heterozygous animals compared to WT. In contrast, a 50% reduction of intercellular coupling did not affect either CV restitution or activation delay. A decrease of 90% Cx43, however, resulted in decreased CV restitution and increased activation delay in RV, but not LV. Reducing excitability but not intercellular coupling by 50% affects CV restitution and activation delay in RV, indicating a higher safety factor for intercellular coupling than excitability in R

Electrocardiographic manifestation of anatomical substrates underlying post-myocardial infarction tachycardias

There are great differences in the type of fibrosis that composes an infarcted area. The type of fibrosis will affect the characteristics of recorded extracellular electrograms. Patchy fibrosis, which is often present in the infarcted zone, gives rise to fractionated electrograms. The amount of fractionation has been shown to increase with infarct aging. In addition, the recording mode being unipolar or bipolar is of importance for interpretation of the electrograms, and it will be shown that the 2 modes are, in fact, complimentary. Surviving myocardial fibers in the infarcted area give rise to conducting tracts that may set up a reentry circuit. Activation in these tracts may be detected during tachycardia as diastolic and during sinus rhythm as late potentials. However, not all sites that generate diastolic potentials during tachycardia will reflect late potentials during sinus rhythm. For ablation of infarct-related tachycardias, the distance between surviving bundles and the recording site is of importance, and this item will be addressed. (c) 2007 Elsevier lnc. All rights reserve

Continuous and discontinuous propagation in heart muscle

Although cardiac muscle has been considered as an electrical syncytium for a long time, several aspects of conduction of the electrical impulse in the heart could not be explained by a continuous approach. Even the simple anisotropic nature of cardiac muscle gives rise to a number of conduction characteristics that contradicts with results from continuous models. It is, however, evident that cardiac conduction must be discontinuous in nature owing to recurrent resistive discontinuities caused by the cellular interconnections. In this review, the role of discontinuities at the cellular and macroscopic level on cardiac propagation will be discusse

Validity, acceptability, and procedural issues of selection methods for graduate study admissions in the fields of science, technology, engineering, and mathematics: a mapping review

Abstract This review presents the first comprehensive synthesis of available research on selection methods for STEM graduate study admissions. Ten categories of graduate selection methods emerged. Each category was critically appraised against the following evaluative quality principles: predictive validity and reliability, acceptability, procedural issues, and cost-effectiveness. The findings advance the field of graduate selective admissions by (a) detecting selection methods and study success dimensions that are specific for STEM admissions, (b) including research evidence both on cognitive and noncognitive selection methods, and (c) showing the importance of accounting for all four evaluative quality principles in practice. Overall, this synthesis allows admissions committees to choose which selection methods to use and which essential aspects of their implementation to account for

Peer-instructed seminar attendance is associated with improved preparation, deeper learning and higher exam scores : A survey study

Background: Active engagement in education improves learning outcomes. To enhance active participation in seminars, a student-centered course design was implemented and evaluated in terms of self-reported preparation, student motivation and exam scores. We hypothesized that small group learning with intensive peer interaction, using buzz-groups followed by plenary discussion, would motivate students to prepare seminar assignments at home and to actively engage in the seminars. Active engagement involved discussion of the preparatory assignments until consensus was reached. Methods: In total seven seminars were scheduled in a 10-week physiology course of an undergraduate Biomedical Sciences program. After each seminar, students were asked to fill out their perceptions of preparation and quality of the seminar (deepening of knowledge and confidence in answers) on a five-point scale using electronic questionnaires. Student motives were first collected using open questions. In the final questionnaire students were asked to indicate on a five-point scale how each motive was perceived. Students overall explanations why they had learned from seminars were collected via open questions in the final questionnaire. One hundred and twenty-four students of the cohort from November 2012 to February 2013 (82.6 %) voluntarily participated. Students' motives to prepare and attend seminars were analyzed by inspection of descriptive statistics. Linear regression analysis was conducted to relate student preparation to the quality of seminars, seminar attendance to exam scores, and exam scores to the quality of seminars. Answers to open questions were deductively clustered. Results: Studying the material, training for exams and comparing answers with peers motivated students to prepare the seminars. Students were motivated to participate actively because they wanted to keep track of correct answers themselves, to better understand the content and to be able to present their findings in plenary discussions. Perceived preparation of peers was positively associated with the perceived quality of seminars. Also, seminar attendance was positively associated with exam scores. Students' overall explanations suggest that discussing with peers and applying knowledge in pathophysiology cases underlies this association. Conclusion: Discussion with well-prepared peers during seminars improves student perceptions of deeper learning and peer-instructed seminar attendance was associated with higher exam scores

Cardiac connexins and impulse propagation

Gap junctions form the intercellular pathway for cell-to-cell transmission of the cardiac impulse from its site of origin, the sinoatrial node, along the atria, the atrioventricular conduction system to the ventricular myocardium. The component parts of gap junctions are proteins called connexins (Cx), of which three main isoforms are found in the conductive and working myocardial cells: Cx40, Cx43, and Cx45. These isoforms are regionally expressed in the heart, which suggests a specific role or function of a specific connexin in a certain part of the heart. Using genetically modified mice, the function of these connexins in the different parts of the heart have been assessed in the past years. This review will follow the cardiac impulse on its path through the heart and recapitulate the role of the different connexins in the different cardiac compartments. (C) 2009 Elsevier Inc All rights reserve

Fibrosis and Cardiac Arrhythmias

In this review article about fibrosis and arrhythmias, we show that the amount of collagen, a normal element of the heart muscle, increases with age and in heart disease. The relation between fibrosis and electrophysiological parameters such as conduction, fractionation of electrograms, abnormal impulse initiation as well as arrhythmogenicity is discussed. Next to the amount of fibrosis, we offer data suggesting that collagen texture too plays a role in conduction slowing and arrhythmia vulnerability. Data are shown revealing that fibrosis can also be induced by reduced sodium channel and connexin43 expression. Finally contrast-enhanced magnetic resonance to detect fibrosis and ventricular tachycardia vulnerability in a noninvasive way as well as a reduction of fibrosis and arrhythmogenicity by inhibition of the renin-angiotensin-aldosterone system is discussed