Effects of Cardiac Resynchronization Therapy on Diastolic Function: Evaluation by Radionuclide Angiography

While the beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function have been demonstrated, no information is available regarding its effects on LV diastolic function during exercise. Using radionuclide angiography, we prospectively evaluated the effects of CRT on diastolic function at rest and during exercise in 15 patients consecutively referred for CRT. All patients underwent equilibrium Tc⁹⁹ radionuclide angiography with bicycle exercise performed (1) at baseline; (2) immediately after CRT implantation, in spontaneous rhythm and during CRT; and (3) after 3 months of biventricular stimulation. Diastolic function was assessed by measurements of peak filling rate (PFR). At baseline, activation of biventricular stimulation influenced PFR neither at rest (1.06 ± 0.34 vs 1.07 ± 0.50 mL/s during spontaneous rhythm, P = 0.9) nor during exercise (1.45 ± 0.62 vs 1.33 ± 0.48 mL/s, P = 0.3). At 3 months, improvements were observed in New York Heart Association functional class and systolic function. By contrast, no improvement in diastolic function was observed either at rest (PFR = 1.11 ± 0.45 vs 1.07 ± 0.50 mL/s in spontaneous rhythm at baseline, P = 0.6) or during exercise (1.23 ± 0.50 vs 1.33 ± 0.48 mL/s, P = 0.2). These observations indicate that the intermediate benefits conferred by CRT on LV systolic function at rest and during exercise were not accompanied by similar improvements in diastolic function .     

Temperature May Be an Appropriate Sensor for Chronotropically Incompetent Patients with Postural Syncope

Chronotropically incompetent patients benefit most from sensor driven rate response during exercise. Postural syncope may occur despite the chronotropic response because of the failure of currently available sensors to respond physiologically to postural changes. Seven chronotropically incompetent patients with postural syncope who had a dual chamber rate adaptive pacemaker (Circadia^R) that modulates heart rate in response to temperature change were studied with respect to: (1) response to exercise: and (2) head-up tilt (HUT). During exercise, continuous-wave Doppler of aortic velocities and two-dimensional echocardiographic derived measurements of left ventricular systolic function were used to assess cardiac function. Patients exercised longer (by an average of 168 sec) in the DDDF/compared to the DDl mode (P = 0.013). Increase in exercise duration was due mostly to the sensor driven increase during DDDH pacing. During DDDR pacing, heart rate increased from 71 ± 6 to 121 ± 17 ppm compared to 70 ± 1 to 103 ± 21 ppm for the DDl pacing (P = 0.038). Stroke volume as assessed by Doppler derived stroke distance (SD) contributed more significantly to the cardiac output increase during exercise in the DDl mode (SD increased from 13.4 ± 4 to 18 ± 7 cm in DDl compared to 13 ± 4 to 14 ± 2 cm in DDDR mode), although these mechanisms were insufficient to fully compensate for failure of appropriate chronotropic response. In response to the HUT, right ventricular temperature increased from 36.78°C ± 0.29°C to 36.89±± 0.28°C (P = 0.0002), and heart rate increased from 54 ± 3 to 71 ± 8 ppm (P = 0.0003) in the DDDR mode. No significant change in heart rate occurred in the DDl mode in response to the HUT. Strong positive correlation of temperature and heart rate was noted in all patients in response to HUT (P = 0.001, R²= 0.755–0.976). We conclude that temperature sensor responds physiologically to exercise and HUT. Therefore, temperature sensing rate adaptive dual chamber pacing may be appropriate for chronotropically incompetent patients with posture related syncope.     

Anatomy and Electrophysiology of the Human AV Node

The atrioventricular node (AVN) has mystified generations of investigators over the last century and continues today to be at the epicenter of debates among anatomists, experimentalists, and electrophysiologists. Over the years, discrepancies have remained in regard to correlating components of AVN structure to function, as evidenced by studies from microelectrodes, optical mapping, and the electrophysiology laboratory. Historically, the AVN has been defined by classical histological methods; however, with recent advances in molecular biology techniques, a more precise characterization of structure is becoming attainable. Distinct molecular compartments are becoming apparent based on connexin staining and genotyping, providing new insight into previously characterized functional aspects of the AVN and its surrounding structures. Advances in optical mapping have provided a unique opportunity for correlating structure and function—unmasking properties of the native AVN pacemaker and providing further insight into basic mechanisms involved in AV conduction. Additionally, procurement of explanted human hearts have provided a unique opportunity to further characterize the human AVN structurally and functionally with both molecular biology techniques and optical mapping. With the elucidation of basic elements of both structure and function via molecular investigation and optical mapping, new opportunities are becoming apparent in utilizing the unique properties of the AVN for pursuing novel clinical applications relevant to clinical electrophysiology. (PACE 2010; 33:754–762)     

Impact of anesthetic agents on cerebrovascular physiology in children

The role of the pediatric neuroanesthetist is to provide comprehensive care to children with neurologic pathologies. The cerebral physiology is influenced by the developmental stage of the child. The understanding of the effects of anesthetic agents on the physiology of cerebral vasculature in the pediatric population has significantly increased in the past decade allowing a more rationale decision making in anesthesia management. Although no single anesthetic technique can be recommended, sound knowledge of the principles of cerebral physiology and anesthetic neuropharmacology will facilitate the care of pediatric neurosurgical patients.     

Health‐related lifestyle,physical and mental health in children of alcoholic parents

Aim. To identify potential differences between children of alcoholics (COAs) and controls in their health‐related lifestyle, mental and physical health. Methods. The recruitment of COAs took place in inpatient and outpatient treatment and rehabilitation units. Controls were recruited in elementary and high schools. 57 COAs (72% response rate) and 84 controls (88% response rate) aged between 12 and 18 years completed a postal questionnaire about their health‐related lifestyle, and mental and physical health. Results. Bivariate analysis showed that COAs' families have higher unemployment rates and lower economic status (P = 0.000). COAs reported poorer school performance (P = 0.000), spending more time in sedentary (television: P = 0.000, Internet: P = 0.014, music: P = 0.040) and less time in physical activities (P = 0.048), having poorer eating habits (fruits and vegetables: P = 0.001, sweets: P = 0.001, fast food: P = 0.000, soft drinks: P = 0.004), a higher substance use (cigarettes: P = 0.030; marijuana: P = 0.564, heavy drinking: P = 0.050) and more mental health difficulties (emotional symptoms: P = 0.015, conduct problems: P = 0.012, suicidal tendencies: P = 0.007, mental disorder: P = 0.040). Among COAs, girls reported more emotional and somatic symptoms compared to boys (P = 0.020 and P = 0.047, respectively). Multivariate analysis showed that after controlling for socioeconomic status, significant mental health and health‐related lifestyle inequalities between COAs and controls persist. Conclusion. Our findings suggest that COAs have a less healthy lifestyle and more mental health difficulties above and beyond the poorer economic environment they live in.[Serec M, ?vab I, Kol?ek M, ?vab V, Moesgen D, Klein M. Health‐related lifestyle, physical and mental health in children of alcoholic parents. Drug Alcohol Rev 2012;31:861–870]     

Virtual Electrode Effects in Transvenous Defibrillation-Modulation by Structure and Interface: Evidence from Bidomain Simulations and Optical Mapping

Virtual Electrodes, Bidomain Model, and Defibrillation. Introduction : Our goal in this combined modeling and experimental study was to gain insight into the transmembrane potential changes in defibrillation conditions, namely, when shocks are delivered by an implantable cardioverter defibrillator (ICD). Two hypotheses concerning the presence and characteristics of virtual electrode effects (VEE) during an ICD shock were tested numerically and experimentally: (H1) anisotropy-dependent VEE are induced over a considerable portion of the "bulk" myocardium; and (H2) surface (epicardial and endocardial) VEE are generated under special tissue bath conditions and are not fully anisotropy determined.
Methods and Results : Optical mapping was performed on Langendorff-perfused rabbit hearts (n = 4) stained with di-4-ANEPPS. Monophasic shocks were applied during the plateau phase of an action potential through a 9-mm long distal electrode in the right or left ventricle and a 6-cm proximal electrode positioned 3 cm posteriorly to the heart. We modeled the experiment using an ellipsoidal bidomain heart with transmural fiber rotation, placed in a perfusing bath, and subjected to defibrillation shocks delivered by an electrode configuration as described. Our numerical simulations demonstrated VEE occupying a significant portion of the myocardium in the conditions of unequal anisotropy ratios for the intra- and extracellular domains. Statistically significant differences in epicardial polarization patterns were predicted numerically and confirmed experimentally when the interface conditions varied.
Conclusion : The present study concludes that VEE are present in transvenous defibrillation. They are shaped by the combined effect of cardiac tissue characteristics and interface conditions. Because of their size, VEE might contribute significantly to defibrillation outcome.     

High-Resolution Fluorescent Imaging Does Not Reveal a Distinct Atrioventricular Nodal Anterior Input Channel (Fast Pathway) in the Rabbit Heart During Sinus Rhythm

Fluorescent Imaging of AVN. Introduction: We sought to determine the precise pathways of engagement of the AV node during sinus rhythm.
Methods and Results: Langendorff-perfused rabbit hearts were stained with 20 μM of the voltage-sensitive dye di-4-ANEPPS. Preparations containing the right atrium, sinoatrial (SA) and AV nodes, and interatrial septum were subsequently dissected and mapped in vitro using a 16 × 16 photodiode array with an adjustable resolution of 150 to 750 μm per diode. Motion artifacts were eliminated by using 15 mM 2,3-butanedione monoxime (BDM). Activation time-points were defined as (-dF/dt)_max, where F = fluorescence. Isochronal maps of activation were plotted using the triangulation method. In all preparations, spontaneous activation began at the SA node, rapidly spread along the crista terminalis (CrT), entered the AV nodal region via the posterior "slow" pathway, and retrogradely spread to the septal region with a smaller conduction velocity compared to that along the CrT. Collision of anterograde and retrograde wavefronts was frequently observed in the mid-septum. Notably, there was no evidence for the presence of a distinct anterior entrance into the AV node.
Conclusion: Fast pathway conduction during sinus rhythm results from a broad posterior wavefront that envelops the AV node with subsequent retrograde atrial septal activation.     

Hypoxia and Hypothermia Enhance Spatial Heterogeneities of Repolarization in Guinea Pig Hearts:

Spatial Autocorrelation of APDs During Arrhythmogenic Insults. Introduction: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32° to 25°C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length l was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where l is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal θ_L (from 0.530 ± 0.138 to 0.478 ± 0.052 m/sec) and transverse θ_T (from 0.225 ± 0.034 to 0.204 ± 0.021 m/sec) conduction velocities and did not alter θ_L/θ_T or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 ± 18.2 to 46 ± 0.6 msec; P < 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of l from 1.8 ± 0.9 to 1.1 ± 0.5 mm (P < 0.005). Hypothermia caused marked reductions of θ_L, (0.53 ± 0.138 to 0.298 ± 0.104 m/sec) and θ_T (0.225 ± 0.034 to 0.138 ± 0.027 m/sec), increased APDs (128 ± 4.4 to 148 ± 14.5 msec), and reduced l from 2.0 ± 0.3 to 1.3 ± 0.6 mm (P < 0.05). l decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced l measured along the longitudinal (l ₁) and transverse (l _T) axes of cardiac fibers while the ratio l _L/l _T remained constant.