Exploring the Electrophysiologic and Hemodynamic Effects of Cardiac Resynchronization Therapy: From Bench to Bedside and Vice Versa.

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with prolonged QRS duration. In patients with left bundle branch block the altered left ventricular electrical activation results in dyssynchronous, inefficient contraction of the left ventricle. CRT aims to reverse these changes and to improve cardiac function.

Cardiac activation-repolarization patterns and ion channel expression mapping in intact isolated normal human hearts.

Background: The repolarization pattern of the human heart is unknown.

Objective: The purpose of this study was to perform a multisite analysis of the activation-repolarization patterns and mRNA expression patterns of ion channel subunits in isolated human hearts.

Methods: Hearts from 3 donors without reported cardiac disease were Langendorff perfused with the patient's own blood.

Percutaneous microembolization of the left coronary artery to model ischemic heart disease in rats.

Small animal models of myocardial infarction are used for a wide variety of research purposes, but common techniques for generating such models require thoracic surgeries that increase mortality risk and damage important structures, such as the pericardial sac. Here, we describe a technique for modeling myocardial infarction in rats by selective coronary microembolization, which has hitherto been described only in large animals. This technique selectively catheterizes the left coronary artery using a custom-made catheter that is introduced and precisely placed under fluoroscopic guidance.

Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes.

Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes.

Exploring the Electrophysiologic and Hemodynamic Effects of Cardiac Resynchronization Therapy: From Bench to Bedside and Vice Versa.

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with prolonged QRS duration. In patients with left bundle branch block the altered left ventricular electrical activation results in dyssynchronous, inefficient contraction of the left ventricle. CRT aims to reverse these changes and to improve cardiac function.

New electrocardiographic criteria to differentiate acute pericarditis and myocardial infarction.

Objective: Transmural myocardial ischemia induces changes in QRS complex and QT interval duration but, theoretically, these changes might not occur in acute pericarditis provided that the injury is not transmural. This study aims to assess whether QRS and QT duration permit distinguishing acute pericarditis and acute transmural myocardial ischemia.

Methods: Clinical records and 12-lead electrocardiogram (ECG) at ×2 magnification were analyzed in 79 patients with acute pericarditis and in 71 with acute ST-segment elevation myocardial infarction (STEMI).

Electrophysiological changes in heart failure and their implications for arrhythmogenesis.

Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors.

Changes in QRS duration and R-wave amplitude in electrocardiogram leads with ST segment elevation differentiate epicardial and transmural myocardial injury.

Background: Acute transmural ischemia increases QRS duration and R-wave amplitude owing to depressed intramyocardial activation. Theoretically, when myocardial injury is confined to the epicardium, the intramyocardial activation is preserved without affecting QRS duration.

Objective: The purpose of this study was to distinguish epicardial from transmural myocardial injury based on the analysis of the QRS complex in leads with ST segment elevation.

The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure.

Aim: To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF).

Methods And Results: In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.

Force frequency relationship of the human ventricle increases during early postnatal development.

Understanding developmental changes in contractility is critical to improving therapies for young cardiac patients. Isometric developed force was measured in human ventricular muscle strips from two age groups: newborns (<2 wk) and infants (3-14 mo) undergoing repair for congenital heart defects. Muscle strips were paced at several cycle lengths (CLs) to determine the force frequency response (FFR).

Transmural dispersion of refractoriness and conduction velocity is associated with heterogeneously reduced connexin43 in a rabbit model of heart failure.

Background: Heterogeneity of repolarization and conduction is a potential source of arrhythmogenesis. In heart failure (HF), intercellular coupling is reduced and heterogeneities may become evident because of reduced intercellular coupling.

Objective: This study sought to investigate connexin43 (Cx43) expression, conduction velocity (CV), refractoriness and inducibility of arrhythmias at multiple sites of the left ventricle during HF.

Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and beta2 receptors.

Dopamine is used to treat heart failure, particularly after cardiac surgery in infants, but the mechanisms of action are unclear. We investigated differences in the effect of dopamine on L-type calcium current (I(Ca)) between newborn (NB, 1-4 days) and adult (AD, 3-4 mo) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts.

Larger cell size in rabbits with heart failure increases myocardial conduction velocity and QRS duration.

Background: Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations.

Methods And Results: HF was induced by pressure-volume overload.

Conduction slowing by the gap junctional uncoupler carbenoxolone.

Background: Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction.

The OAR/aristaless domain of the homeodomain protein Cart1 has an attenuating role in vivo.

Aristaless-related genes encode a structurally defined group of homeoproteins that share a C-terminal stretch of amino acids known as the OAR- or aristaless domain. Many aristaless-related genes have been linked to major developmental functions, but the function of the aristaless domain itself is poorly understood. Expression and functional studies have shown that a subgroup of these genes, including Prx1, Prx2, Alx3, Alx4 and Cart1, is essential for correct morphogenesis of the limbs and cranium.

Remodeling of gap junctions in mouse hearts hypertrophied by forced retinoic acid signaling.

Background: Beta-MHC-hRARalpha transgenic mice express a constitutively active (truncated) form of the human retinoic acid receptor which triggers development of dilated cardiomyopathy. In those hearts, we studied expression of gap junction proteins in relation to electrical impulse propagation.

Methods And Results: As compared to wildtype mice, hearts of 4-6 month old mice with 7-12 inserted hRARalpha copies are marked by an increased heart weight/body weight- and heart weight/tibia length ratio.