[Economic issues and public alcohol abuse prevention policies in France].

Objective: To analyse the impact of the alcohol market on the implementation of strong-willed public alcohol abuse prevention policies based on a critical review of the literature. Method: Documentary research and analysis of the alcohol market economic data were performed. An overview of public alcohol abuse prevention policies was conducted from a historical perspective by distinguishing drunkenness control policies, protection of vulnerable populations, and the fight against drink driving and drinking in the workplace.

Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study.

Background: Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site before a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue is unknown.

The perplexing complexity of cardiac arrhythmias: beyond electrical remodeling.

Cardiac arrhythmias continue to pose a major medical challenge and significant public health burden. Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality. In addition, more than 250,000 Americans each year suffer ventricular arrhythmias, often resulting in sudden cardiac death.

Cell size and communication: role in structural and electrical development and remodeling of the heart.

With the advent of new information about alterations of cardiac gap junctions in disease conditions associated with arrhythmias, there have been major advances in the genetic and metabolic manipulation of gap junctions. In contrast, in naturally occurring cardiac preparations, little is known about cell-to-cell transmission and the subcellular events of propagation or about structural mechanisms that may affect conduction events at this small size scale. Therefore, the aim of this article is to review results that produce the following unifying picture: changes in cardiac conduction due to remodeling cardiac morphology ultimately are limited to changes in three morphologic parameters: (1) cell geometry (size and shape), (2) gap junctions (distribution and conductivity), and (3) interstitial space (size and distribution).

Changes in anisotropic conduction caused by remodeling cell size and the cellular distribution of gap junctions and Na(+) channels.

Because gene therapy presents a new frontier in the treatment of arrhythmias, it has become important to know how manipulation of the cellular distribution of proteins changes electrical events within individual cells, and whether these cellular changes affect conduction at the larger macroscopic size scale. However, experimental limitations in cardiac bundles prevent measurement of conduction delays across specific gap junctions, as well as the intracellular distribution of the maximum rate of rise of the action potential (V(max)). In view of these limitations, we used immunohistochemical morphological results as a basis to develop two-dimensional cellular models of neonatal and mature canine ventricular muscle in order to obtain insight into the electrophysiological effects of changes in the cellular distribution of proteins; eg, the major protein of cardiac gap junctions, connexin43.

Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth.

The increased incidence of arrhythmias in structural heart disease is accompanied by remodeling of the cellular distribution of gap junctions to a diffuse pattern like that of neonatal cardiomyocytes. Accordingly, it has become important to know how remodeling of gap junctions due to normal growth hypertrophy alters anisotropic propagation at a cellular level (V(max)) in relation to conduction velocities measured at a macroscopic level. To this end, morphological studies of gap junctions (connexin43) and in vitro electrical measurements were performed in neonatal and adult canine ventricular muscle.

Effects of cardiac microstructure on propagating electrical waveforms.

Electrical waveforms measured during propagation at microscopic level are considerably affected by normal variations in cardiac microstructure as well as by the superfusing fluid. On the basis of evidence we present in this article, we argue that the anisotropic waveform variations discussed here are explained primarily by the associated variations in different microstructural components of myocardial architecture rather than by the effects of the perfusing bath. The results suggest that different components of myocardial architecture have preferential effects on f1.

Extracellular discontinuities in cardiac muscle: evidence for capillary effects on the action potential foot.

It has become of fundamental importance to understand variations in the shape of the upstroke of the action potential in order to identify structural loading effects. One component of this goal is a detailed experimental analysis of the time course of the foot of the cardiac action potential (Vm foot) during propagation in different directions in anisotropic cardiac muscle. To this end, we performed phase-plane analysis of transmembrane action potentials during anisotropic propagation in adult working myocardium.

Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias.

The purpose of this article is to demonstrate how adaptive changes in myocardial microstructure provide mechanisms for emergent new conduction disturbances that initiate reentrant arrhythmias. The mechanisms are based on discontinuous conduction phenomena produced by increases in cellular loading; these increases result from changes in the normal distribution of the gap junctions. Recent studies that at a microscopic level propagation in normal mature cardiac muscle is stochastic.

Nonuniform anisotropy is responsible for age-related slowing of atrioventricular nodal reentrant tachycardia.

Introduction: AV nodal reentrant tachycardia cycle length has been shown to be longer in the elderly population. Microfibrosis associated with aging producing nonuniform anisotropic conduction or changes in membrane ionic properties could explain this finding.

Methods And Results: Forty-five patients (33 women and 12 men) with typical AV nodal reentrant tachycardia were studied to analyze the effects of age on electrophysiologic characteristics of the tachycardia using high-density catheter mapping of the triangle of Koch.

The stochastic nature of cardiac propagation at a microscopic level. Electrical description of myocardial architecture and its application to conduction.

The object of this study is to present evidence that the myocardial architecture creates inhomogeneities of electrical load at the cellular level that cause cardiac propagation to be stochastic in nature; ie, the excitatory events during propagation are constantly changing and disorderly in the sense of varying intracellular events and delays between cells. At a macroscopic level, however, these stochastic events become averaged and appear consistent with a continuous medium. We examined this concept in a two-dimensional (2D) model of myocardial architecture by exploring whether experimentally observed Vmax variability reflected different patterns of intracellular excitation events and junctional delays.

Measuring activation patterns of the heart at a microscopic size scale with thin-film sensors.

To study the spread of excitation in ventricular heart preparations we have designed a fast, high-resolution recording and mapping system. Papillary muscles were dissected from the isolated guinea pig hearts. The preparation was fixed in a tissue bath and superfused with Tyrode solution.

Initiating reentry: the role of nonuniform anisotropy in small circuits.

Until recently only two types of media have been considered to provide the nonuniformities necessary to initiate cardiac reentry: (1) continuous isotropic media with intrinsic repolarization inhomogeneities; and (2) continuous isotropic media free of inhomogeneities in which repolarization nonuniformities are introduced transiently. The purpose of this article is to establish cellular coupling as a basis for arrhythmias by placing a new type of inhomogeneity, nonuniform anisotropy due to sparse side-to-side coupling between cells, in an overall perspective with the other nonuniformities that lead to reentry. Review of experimental and theoretical models of reentry leads to the following picture: with slowed conduction, reentrant circuits diminish in size and the nonuniformities necessary for reentry are provided by nonuniform anisotropy.

Conventional and confocal fluorescence microscopy of collagen fibers in the heart.

The arrangement of collagen fibers has previously been studied with picrosirius red (PSR) staining and brightfield microscopy. We discovered that PSR staining can also be visualized by fluorescence microscopy. PSR-stained collagen was strongly fluorescent using excitation and barrier filters for rhodamine, and distracting background cytoplasmic fluorescence was drastically reduced with phosphomolybdic acid (PMA) treatment before PSR staining.

Cellular Vmax reflects both membrane properties and the load presented by adjoining cells.

This study was designed to test the hypothesis that the electrical load seen at a microelectrode impalement site is sensitive to the direction of propagation of the approaching wavefront as a reflection of an altered spatial relationship between the impalement site and the surrounding microscopic electrical boundaries located up- and downstream. These boundaries correspond to the different sizes and shapes of the impaled and surrounding cells as well as to the distribution of the associated electrical connections between the cells. The effects of changes in these geometric relationships on maximum rate of rise of transmembrane potential (Vmax) were investigated in canine ventricular muscle by measuring Vmax in different cells while the direction of propagation was changed from along the longitudinal axis to the transverse axis of the fibers or the direction of conduction was reversed along either of these axes.

Distribution of gap junctions in dog and rat ventricle studied with a double-label technique.

To assess the distribution of gap junctions in relation to the cardiac myocyte surface in paraffin sections of dog and rat ventricle, the sarcolemma was labeled with wheat germ agglutinin (WGA1) and gap junctions were labeled with antibodies to cardiac muscle gap junction protein connexin43. WGA labeled all of the myocyte sarcolemma, including that in intercalated discs and transverse tubules. Sarcolemmal WGA labeling was often interrupted at the sites of gap junctions, which were found both at the extreme ends of myocytes and along the length of adjacent myocytes.

A multidimensional model of cellular effects on the spread of electrotonic currents and on propagating action potentials.

This study was designed to develop a two-dimensional cellular model of uniform anisotropic muscle and to determine how irregularities of shape and variations in size of cardiomyocytes influence the passive (electrotonic) spread of currents at a microscopic level. A secondary purpose was to determine how the passive transfer of impressed currents across the gap junctions is related to the charge flow across the gap junctions during active propagation of depolarization. The decrease in electrotonic Vm with distance at a large size scale was described by a single exponential in both the longitudinal and transverse directions, as occurs in a continuous anisotropic medium.