Model Of Reentry Research Articles

Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.

To determine specificity of rodent models of arrhythmia for different Vaughan Williams classes of antiarrhythmic drugs, we tested 17 drugs from the four classes in one in vitro and four in vivo models. In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active. Class III drugs (bretylium, clofilium, or melperone did not suppress ouabain arrhythmias, but were active in the mouse chloroform model. In the rat coronary artery ligation model, disopyramide (class I), amefalone and melperone significantly (P less than 0.05) reduced the number of extrasystoles. Propranolol, sotalol, and verapamil (class IV) were less effective. In the rat coronary artery ligation/reperfusion model, all four classes of antiarrhythmic agents were active in vitro (isolated heart) and in vivo (anesthetized rat). Thus, one model of automaticity, the guinea pig ouabain model, detected class I, II, and IV drugs, whereas another automaticity model, the mouse chloroform model, also detected class III agents. The model of reentry induced by ischemia plus reperfusion (rat coronary artery ligation reperfusion) can be recommended as a screen for new antiarrhythmic agents based on its sensitivity to all four classes of antiarrhythmic drugs. The Vaughan Williams class of an antiarrhythmic agent must be determined, however, by additional mechanism studies.

Proarrhythmia: A Paradoxic Response to Antiarrhythmic Agents

Antiarrhythmic drugs may effectively terminate and prevent symptomatic tachycardias, but they may also provoke life-threatening rhythm disturbances. The electrophysiologic mechanisms responsible for proarrhythmia can be extrapolated from the existing models of reentry and abnormal automaticity. Although all antiarrhythmic drugs may cause proarrhythmia with seemingly similar frequency, the profile of the disturbance with each class of agents appears somewhat distinct. All agents may cause an increased frequency of premature beats or new or worsened ventricular tachycardia, but the classic form of proarrhythmia due to type la agents is torsades de pointes. Recent information has provided clues to the underlying mechanism of drug-induced torsades de pointes and has provided a clinical picture of patients with this adverse effect. Types lb and lc agents only rarely precipitate torsades de pointes. The latter, however, may cause a rapid, sustained, monomorphic ventricular tachycardia in certain high-risk patients that can be resistant to resuscitation efforts. Amiodarone may cause a broad variety of arrhythmias that are complicated by their extended duration and difficulty in distinguishing proarrhythmia from simple inefficacy. Proarrhythmia is a relatively common, paradoxic side effect that necessitates the clinician to make careful risk-benefit decisions in choosing antiarrhythmic drug therapy.

Pharmacological characterisation of a re-entry model for atrial tachycardia in conscious dogs

We studied the effects of intravenously administered autonomic agents, the calcium channel blocker diltiazem, and Class I and III anti-arrhythmic agents on a re-entry model for atrial tachycardia in seven conscious dogs. The model was created by a Y-shaped incision in the intercaval region and front free wall of the right atrium. Acetylcholine (30 micrograms.kg-1) transiently but significantly shortened the cycle length of atrial tachycardia (CL) by 9 (SD 5)% while atropine (0.2 mg.kg-1) alone did not change or terminate the rhythm. Isoprenaline (4 micrograms.kg-1) briefly reduced CL, by 13(6)% whereas propranolol (1 mg.kg-1) alone significantly prolonged the CL and terminated the arrhythmia in 50% of the trials. Diltiazem (200 micrograms.kg-1) did not significantly change the CL. Class Ia agents procainamide (30 mg.kg-1) and quinidine (3.5 approximately 20 mg.kg-1, effective doses) increased CL by 60(30) and 43(28)% respectively and terminated the arrhythmias. Class Ib agents, phenytoin (5 and 10 mg.kg-1, cumulative doses), lignocaine (3.2 approximately 7 mg.kg-1), and mexiletine (6 approximately 20 mg.kg-1), prolonged CL by 31(14), 40(15), and 72(13)%; however, consistent conversion of the rhythm occurred only with mexiletine. Ic agents flecainide (0.5 approximately 3 mg.kg-1) and encainide (0.6 approximately 6.4 mg.kg-1) lengthened the CL by 58(17) and 75(43)% and converted the rhythm in all cases. Class III agents clofilium (0.5 mg.kg-1), d-sotolol (3.2 approximately 20 mg.kg-1), and N-acetylprocainamide (15 approximately 120 mg.kg-1) prolonged the CL by 14(4), 16(5), and 19(7)% and terminated the arrhythmia in all trials. The magnitudes of CL prolongation by the Class III agents were significantly smaller than those by the Class Ia, Ib, or Ic agents. These results show that in this re-entrant model for atrial tachycardia endogenous adrenergic but not cholinergic systems play a major role in maintaining impulse propagation and that calcium channel mediated slow inward currents do not participate in the impulse generation processes. Further, using CL as an index, the model serves as a useful tool for differentiating Class III from Class I anti-arrhythmic activities.

Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation.

Available models of circus movement reentry in cardiac muscle and of drug action on reentrant arrhythmias are based on continuous medium theory, which depends solely on the membrane ionic conductances to alter propagation. The purpose of this study is to show that the anisotropic passive properties at a microscopic level highly determine the propagation response to modification of the sodium conductance by premature action potentials and by sodium channel-blocking drugs. In young, uniform anisotropic atrial bundles, propagation of progressively earlier premature action potentials continued as a smooth process until propagation ceased simultaneously in all directions. In older, nonuniform anisotropic bundles, however, premature action potentials produced either unidirectional longitudinal conduction block or a dissociated zigzag type of longitudinal conduction (a safer type of propagation, similar to transverse propagation). Directional differences in the velocity of premature action potentials demonstrated that anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm2, even with very short refractory periods. Quinidine produced Wenckebach periodicity, which disappeared after acetylcholine shortened the action potential. Quinidine also produced use-dependent dissociated zigzag longitudinal conduction in the older, nonuniform anisotropic bundles but not in the young, uniform anisotropic bundles. The electrophysiological consequence was that propagation events differed in an age-related manner in response to the same modification of the sodium conductance. The electrical events at microscopic level showed that conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy) provide a primary mechanism for reentry to occur within very small areas (1-2 mm) due to a variety of propagation phenomena that do not occur in tissues with tight electrical coupling in all directions.

Generation of arrhythmias in myocardial ischemia and infarction

In recent years an enhanced interest among researchers combined with the availability of new technologies has increased our knowledge of the mechanisms that generate arrhythmias in patients with ischemic heart disease. Convincing evidence has been obtained to support the occurrence of reentry in ischemic myocardium. This has been especially apparent in canine studies in the surviving layers overlying infarctions several days after coronary occlusion. In this planar model, the reentry circuit forms a figure-8 configuration around an arc of functional block due to refractoriness; the center of the arc is the site of unidirectional block and reentry. The reentry circuit is sustained by wavefronts of activation encircling segments in which the tissue on either side is alternately receptive and refractory, a variant of the leading circle model of reentry. The relatively prolonged refractoriness in ischemic tissue is due to time-dependent refractoriness, i.e., postrepolarization refractoriness, which is most prominent in more severely depolarized cells. Slow conduction is related in part to primary depression of the fast channels. There is a great variation in refractory periods in ischemic tissue because of variation in action potential duration and in the duration of time-dependent refractoriness. The depolarized resting potentials of cells in acute ischemia are due in part to extracellular accumulation of potassium and intracellular accumulation of calcium. In the latter stages of ischemia it is likely that abnormalities of ion distribution across the sarcolemma play a role. It has also been demonstrated that ischemic Purkinje fibers show abnormal automaticity, i.e., enhanced phase 4 depolarization at depolarized diastolic potentials, and afterdepolarizations with triggered firing. The relative importance of these 2 phenomena in arrhythmias in vivo is controversial. There is evidence that reflection may be a mechanism for the generation of ectopic beats in the first few minutes of acute ischemia.

Social role valorization: a model for community reentry

Social role valorization: a model for community reentry

Reentrant ventricular arrhythmias in the late myocardial infarction period. 12. Spontaneous versus induced reentry and intramural versus epicardial circuits

One to 5 days after one-stage ligation of the left anterior descending coronary artery in dogs, reentrant excitation can be induced by programmed premature stimulation in the surviving electrophysiologically abnormal, thin epicardial layer overlying the infarct. In experiments in four dogs, reentrant excitation occurred "spontaneously" during a regular sinus or atrial rhythm. A tachycardia-dependent Wenckebach conduction sequence in a potentially reentrant pathway was the initiating mechanism for spontaneous reentrant tachycardias and was the basis for both manifest and concealed reentrant extrasystolic rhythms. In all dogs showing spontaneous reentry, reentrant excitation could also be induced by premature stimulation at cycle lengths much shorter than those associated with spontaneous reentry, and induced reentrant circuits were always different from those during spontaneous reentry. In two dogs, the reentrant circuit was located intramurally in close proximity to a patchy septal infarction. The study illustrates that irrespective of the anatomic localization of reentrant circuits (epicardial or intramural), their dimension (large or small) or their mechanism of initiation (programmed premature stimulation or "spontaneous"), reentrant excitation always occurred in a figure 8 configuration (or a modification thereof). The figure 8 model, rather than the ring model or the leading circle model, may be the common model of reentry in the mammalian heart.

Calculation of SANS intensity for polyethylene: effect of varying fold planes and fold plane roughening

The intensity of the small angle neutron scattering (SANS) for polyethylene crystallized in the lamellar habit from the melt at large supercoolings is calculated for μ = 0.01 to μ = 0.14 [ μ = ( 4π λ ) sin ( θ 2 ) ]. Computations are made on models which allow various amounts and types of chain folding and varying degrees of ‘tight’ or ‘regular’ folds. The models that fit the SANS data best have folding along lattice planes in which the stem separation is larger than 0.5 nm (5 Å) or which allow for fold plane roughening on a variety of fold planes. the ‘leapfrog’ type folds mentioned by Sadler were also considered, and a possible cause for their existence suggested. As an example, the variable cluster model gives a good account of the SANS data with the surface roughening suggested by nucleation theory with fold planes [110], [200], and [310], or a mixture. Even though the conditions of crystallization used in preparing the SANS specimens (large supercoolings) were conducive to the maximum surface disorder, the probability of ‘tight’ or ‘regular’ folding, p tf , was found to be ∼0.7 for the best models. This corresponds closely to the theoretical lower bound p tf = 2 3 which is rigorous for the case of non-tiled stems. The probability of strictly adjacent re-entry in a single specified fold plane, p ar , was ∼0.4 to ∼0.7 depending on the particular model chosen. The best models fit not only the SANS data, but also the liquid and crystal density, degree of crystallinity, and characteristic ratio (or radius of gyration). None of the models show the density anomaly inherent in the switchboard or random re-entry models of Yoon and Flory.

Polymer crystallization from the melt at large undercoolings

AbstractConsideration of crystallization kinetics in high‐molecular‐weight polymers shows that adjacent reentry is unlikely in melt crystallization and that sections of individual chains will crystallize concurrently at several sites. Hence the characteristic crystallization process will be that of a loop of chain with both ends attached to different sites on the crystal surface. Analysis of this process leads to predictions of crystallinity values for various conditions of chain mobility in the crystal and of entanglements in the amorphous regions. Observations on polymers crystallized at high undercoolings where a crystallinity of about 30% is usually observed suggest that the common case is that of a highly entangled amorphous layer and rapid, local annealing of the chains but with no long‐range motion in the crystal. This model of loop crystallization is shown to agree with available small‐angle neutron scattering data. The overall crystallization kinetics are in accord with surface nucleation controlled growth which also arises out of the Lauritzen‐Hoffman adjacent reentry model and has been shown to fit experimental results on growth rates.

Structural studies of polysiloxanes: crystal structure and fold conformation of poly(tetramethyl- p-silphenylene siloxane)

The crystal structure of poly(tetramethyl- p-silphenylene siloxane) has been determined using X-ray diffraction data from drawn fibres. The unit cell is tetragonal with dimensions a = b = 0.902 nm and c (fibre axis) = 1.543 nm. The space group is P4 32 12 and the unit cell contains four monomer units. Each chain adopts a 2 1 helical conformation so that two chains run through the unit cell. The crystallographic asymmetric portion of the molecule is one half of a monomer unit with the oxygen atom and the centre of mass of the phenyl group at special positions. The two halves of a monomer are symmetry related by a diad axis perpendicular to the fibre axis. In addition, this polymer [poly (TMPS)] can crystallize in the form of chain-folded lamellae, and detailed models for the fold structure have been examined using computer model building techniques. A unique conformational model was found for adjacent re-entry fold models and a stereochemically acceptable fold can be obtained using a single residue. The only acceptable models encompassing two or three residues in the fold turn out to be only small perturbations of the single residue adjacent re-entry fold.

Effect of procainamide and lidocaine on ventricular automaticity and reentry during acute coronary occlusion

A model was developed to study ventricular automaticity and reentry in the heart of open chest dogs during myocardlal ischemia. Atrioventricular (A-V) block and the resultant idioventricular rhythm were induced by surgical destruction of the His bundle, and acute myocardial ischemia was produced by ligation of the left anterior descending coronary artery. The ventricle was paced by basic stimuli, and one or two premature beats were introduced at various coupling Intervals after the 10th basic beat. Two different types of response to these premature beats could be observed: (1) rapidly repetitive beats or fibrillation due to reentry after early premature beats, and (2) the appearance of escape beats from idioventricular automatic fibers after late premature beats. With this model of ventricular reentry and automaticity, the effect of procainamide (group I antiarrhythmic agent) was studied in 12 dogs, and that of lidocaine (group II) in 13 dogs. Both procainamide and lidocaine were effective in decreasing automaticity since they significantly increased postextrasystolic escape intervals of idloventricular beats. Although procainamide failed to abolish the reentrant beats induced by early premature beats in all 12 dogs, lidocaine abolished these beats in 10 of 13 dogs. The results indicate that lidocaine is much more effective than procainamide in preventing ventricular reentrant activity induced by early premature beats.

Sinus nodal reentry: Effect of quinidine

The recently developed experimental model for sinus nodal reentry was used to assess the effect of quinidine in 20 dogs. Sinus nodal reentry was demonstrated in 19 dogs and was abolished in all dogs when plasma levels of quinidine (average 4.8 mg/liter) were in the therapeutic range after an average infusion time of 7 minutes. Characteristically in 15 dogs, quinidine increased atrial refractoriness and slowed atrial conduction so that the arrival time of the atrial premature beat (A 2) in the region of the sinus node fell outside the reentry zone and sinus nodal reentry was terminated. Conduction delay along the reentrant pathway preceded loss of sinus nodal reentry in 6 of these 15 dogs, thereby suggesting that quinidine-induced conduction delay and block along the reentrant pathway may be another mechanism for abolishing sinus nodal reentry. In the four remaining dogs in which sinus nodal reentry was abolished when the premature beat continued to fall within the reentry zone, the latter mechanism seems likely.

Statistical-Mechanical Study of Stability of Folded-Chain Polymer Crystals with Irregular Fold Surfaces

A model of folded-chain crystals of polymers is considered, in which the length of crystalline sequences between folds is assumed to be uniform, while the number of segments comprising the folds is allowed to vary. The partition function is formulated by the generating function technique, with the fixed crystalline layer thickness introduced as an additional parameter of the system. The random-walk problem in the presence of a barrier, as the representation of folds, is solved for simple and body-centered cubic lattices. As variants of the basic model, the two ends of the fold are either assumed constrained in adjacent positions in the adjacent re-entry model, or are allowed at an arbitrary separation in the random re-entry model. The free energy of the system as a function of crystalline layer thickness exhibits no minimum, confirming the extend-chain crystals as the thermodynamically most stable. As the temperature is raised toward the melting point, the number of segments in folds increases beyond bound in the random re-entry model; while they remain about 10 in the adjacent re-entry model. In both models the size of the amorphous chain ends grows much faster than that of folds with increasing temperature. The frequency distribution of fold sizes is very broad. Even when the majority of folds consists of tight loops of a small number of segments, the fraction of very large folds is small but still significant. The entropy term of the surface free energy, calculated for the random and adjacent re-entry models, differs by as much as 50 erg/cm2.

Population Exposure Probability Model for Random Reentry of a Radioisotope Source

A satellite carrying radioactive material in a near-Earth orbit has a finite probability of reentering before the radioactivity has decayed to a harmless level. If the reentry is unplanned, it is n...

Time-resolved spectra for some simple laboratory simulated reentry models

The time-resolved spectra for some spherical and conical models under simulated reentry conditions in a free-flight range have been obtained using a large aperture slitless spectrograph in conjunction with an image converter camera. The spectra from the shock cap, the immediate proximity of the model, and the near wake region of the flow are spatially resolved. In the wake region, the spectra for some ablating models contain, in addition to atomic lines characteristic of the model materials, such molecular band systems as C 2, CH, CN, Cu 2, CuO, CuF, and AlO. Some comparisons are made between the spectra obtained above and the radiometric data using wideband filters. Extension of the experiment into the far wake region of the flow using a high gain image intensifier will be discussed.

Time-resolved spectra for some simple laboratory simulated reentry models

The time-resolved spectra for some spherical and conical models under simulated reentry conditions in a free-flight range have been obtained using a large aperture slitless spectrograph in conjunction with an image converter camera. The spectra from the shock cap, the immediate proximity of the model, and the near wake region of the flow are spatially resolved. In the wake region, the spectra for some ablating models contain, in addition to atomic lines characteristic of the model materials, such molecular band systems as C 2 , CH, CN, Cu 2 , CuO, CuF, and AlO. Some comparisons are made between the spectra obtained above and the radiometric data using wideband filters. Extension of the experiment into the far wake region of the flow using a high gain image intensifier will be discussed.

Inhomogeneous conduction in the A-V node: A model for re-entry

Inhomogeneous conduction in the A-V node as well as concealed and manifest A-V nodal re-excitation were observed in isolated, perfused rabbit hearts during the course of electrophysiologic studies on A-V transmission in 98 experiments. Through the use of two simultaneously impaled glass microelectrodes in the A-V junctional tissues, spread of excitation in this region was studied with reference to the atrial and ventricular electrograms. Re-excitation followed in the wake of prolonged A-V conduction and occurred in an area of the A-V transmission system in which conduction was most severely depressed. In some instances, inhomogeneity of conduction permitted a slow but successful transmission in one region of the specialized conducting system with diminution in another. Thus, the impulse was permitted to travel preferentially through the left side of the A-V node, turn and be transmitted in a retrograde fashion along the right side of the A-V junction, where forward conduction was blocked. These results were obtained in the presence of both sinus and A-V junctional beats, and appeared to be compatible with the concept of re-entry.