Transverse Conduction Velocity Research Articles

Effects of halothane and enflurane on ventricular conduction, refractoriness, and wavelength: a concentration-response study in isolated hearts.

Effects of halothane and enflurane on ventricular conduction, anisotropy, duration and dispersion of refractory periods, and wavelengths were studied, and putative antiarrhythmic or arrhythmogenic properties on ventricles were discussed. High-resolution epicardial mapping system was used to study the effects of 1, 3, and 5 vol% halothane and enflurane in 30 isolated rabbit hearts. Ten hearts were kept intact to study the effects on spontaneous sinus cycle length (RR interval), perfusion pressure, and the occurrence of spontaneous dysrhythmias. In 20 other hearts, a thin epicardial layer was obtained (frozen hearts) to study ventricular conduction velocity, ventricular effective refractory period (VERP in four sites) and wavelengths. Halothane induced a concentration-dependent lengthening of RR interval, whereas enflurane did not. Both agents slowed longitudinal and transverse ventricular conduction velocity with no anisotropic change. Ventricular effective refractory period was prolonged at 1 vol% and was shortened at higher concentrations, with no significant increase in dispersion. Ventricular longitudinal and transverse wavelengths decreased in a concentration-dependent manner. Although changes in wavelengths could express proarrhythmic effects of volatile anesthetics, no arrhythmia occurred in spontaneously beating hearts or in frozen hearts. The ventricular electrophysiologic effects of halothane and enflurane were slight, suggesting that both agents are unable per se to induce functional conduction block and therefore reentrant ventricular arrhythmias.

Effects of the gap junction uncoupler palmitoleic acid on the activation and repolarization wavefronts in isolated rabbit hearts.

1. The heart normally acts as an electrical syncytium coupled via gap junctional channels. Since closure of these channels has been considered arrhythmogenic, we wanted to elucidate, how activation and repolarization wavefronts are altered during progressive pharmacological gap junctional uncoupling. 2. We used the well known gap junction uncoupler palmitoleic acid (PA). The specificity of PA was tested in rabbit papillary muscles, which exhibited slowed conduction without affecting action potential morphology. We submitted isolated rabbit hearts (Langendorff-technique) to increasing concentrations of palmitoleic acid (0.2, 1, 2, 5, 10, 20 microM), while 256 channel epicardial potential mapping was carried out. 3. In presence of PA activation recovery intervals (ARI) at the 256 electrodes became highly inhomogeneous with a dramatic increase in the dispersion of activation recovery intervals (from 6 to 35 ms, P>0.01; EC50=7 microM), while the mean ARI-duration at 256 sites remained stable. PA led to marked alterations of the activation pattern, expressed as percentage of unchanged activation vectors (reduction from 32 to 10%, P<0.01, EC50=3.3 microM), to prolongation of atrioventricular conduction time (from 58 to 107 ms, P<0.01; EC50=8 microM) of total activation time (from 7 to 14 ms, P<0.05, EC50=11 microM) and of QRS-complex-duration. 4. In additional experiments the ventricle was paced via a bipolar electrode during the mapping procedure. From the isochrones longitudinal and transversal velocities were assessed showing that PA reduced transversal conduction velocity more distinctly than longitudinal. 5. With regard to maximum effects and EC50 values we conclude that gap junction uncoupling by PA mainly affects atrioventricular conduction, ARI-dispersion and ventricular activation pattern. As important arrhythmogenic effects of uncoupling enhancement of dispersion with concomitant disturbation of the normal activation pattern and slowing of conduction might be considered.

Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

Electrophysiological effects of acute dilatation in the isolated rabbit heart: cycle length-dependent effects on ventricular refractoriness and conduction velocity.

Acute ventricular dilatation has important electrophysiological effects: Dilatation shortens action potential duration and refractoriness without an apparent effect on conduction velocity. These effects have been implicated as a potential mechanism of arrhythmias in patients with congestive failure. Because the influence of cycle length on these phenomena has not been studied, we examined the effects of dilatation during ventricular pacing at cycle lengths from 1000 to 150 ms. Thin epicardial layers were created in isolated, perfused rabbit left ventricles (n=7). A fluid filled latex balloon was secured in the left ventricle to dilate the left ventricle. Mapping was performed with 248 epicardial electrodes. Longitudinal conduction velocity (76+/-1 cm/s; mean+/-SEM) and transverse conduction velocity (26+/-1 cm/s) were not influenced by dilatation at any cycle length. In contrast, the effects of dilatation in decreasing left ventricular effective refractory period (ERP) were significantly greater at shorter drive cycle lengths: The decrease in ERP was 2+/-2 ms (a 1% change) at a drive cycle length of 1000 ms and 18+/-4 ms (a 20% change) at a drive cycle length of 150 ms. In 10 additional intact, isolated perfused rabbit hearts, dilatation decreased ERP to a greater degree during 250 ms drive cycle length pacing than during pacing at 400 ms (25+/-4 versus 16+/-3 ms; P=.01). Acute dilatation exaggerates the normal rate-dependent shortening of refractoriness but does not influence transverse or longitudinal conduction velocity. This observation suggests that the electrophysiological effects of acute dilatation may be greater during tachycardia than at slower cycle lengths. This may have implications for arrhythmias in patients with congestive heart failure.

Effects of ketamine on ventricular conduction, refractoriness, and wavelength: potential antiarrhythmic effects: a high-resolution epicardial mapping in rabbit hearts.

The aims of the study were to verify the effects of ketamine on ventricular conduction velocity and on the ventricular effective refractory period, to determine its effects on anisotropy and on homogeneity of refractoriness, and to use wavelength to determine whether ketamine has antiarrhythmic or arrhythmogenic properties. A high-resolution epicardial mapping system was used to study the effects of 50, 100, 150, and 200 microM racemic ketamine in 15 isolated, Langendorff-perfused rabbit hearts. Five hearts were kept intact to study the effects of ketamine on spontaneous sinus cycle length (RR) interval and its putative arrhythmogenic effects. In 10 other hearts, a thin epicardial layer was obtained by an endocardial cryoprocedure (frozen hearts) to study ventricular conduction velocity, ventricular effective refractory periods (five sites), and ventricular wavelength. Ketamine induced a concentration-dependent lengthening of the RR interval. Ketamine slowed longitudinal and transverse ventricular conduction velocity with no anisotropic change, and it prolonged the ventricular effective refractory period with no significant increase in dispersion. Ventricular longitudinal and transverse wavelengths tend to increase, but this was not statistically significant. Finally, no arrhythmia could be induced regardless of the ketamine concentration. Ketamine slowed ventricular conduction and prolonged refractoriness without changing anisotropy or increasing dispersion of refractoriness. Although these effects should result in significant antiarrhythmic effects of ketamine, this should not be construed to suggest a protective effect in ischemic or other abnormal myocardium.

Optical mapping reveals that repolarization spreads anisotropically and is guided by fiber orientation in guinea pig hearts.

Guinea pig hearts were stained with a voltage-sensitive dye and imaged on a photodiode array to record fluorescent action potentials (APs) from 124 sites. Activation and repolarization patterns were recorded from the epicardium during stimulation at different loci and correlated with the underlying fiber architecture. Endocardial APs were recorded by inserting a light guide into the ventricular cavity or by dissecting out the ventricular free wall to expose the endocardium. In hearts paced on the right atrium to simulate sinus rhythm, activation emerged synchronously over a large area of the ventricular epicardium and spread laterally in 5 to 7 ms. The apparent longitudinal and transverse velocities were 2.66 +/- 0.11 and 1.65 +/- 0.09 m/s (n = 12). In contrast, repolarization began near the apex on the endocardium and spread transmurally in 6 +/- 1.3 ms (n = 12) and then anisotropically along the epicardium in 25 to 30 ms with apparent maximum (0.53 +/- 0.11 m/s) and minimum (0.31 +/- 0.10 m/s) repolarization velocities that aligned with the longitudinal and transverse axes of epicardial fibers. When paced on the epicardium, activation of intact hearts (n = 12) and perfused sheets (n = 8) was anisotropic, with longitudinal (0.85 +/- 0.05 m/s) and transverse (0.44 +/- 0.04 m/s) conduction velocities that aligned with the epicardial fiber orientation. When activation was initiated at different sites on the epicardium, repolarization always began near the apex and exhibited patterns similar to those obtained under right atrial pacing, but with slower longitudinal (0.41 +/- 0.09 m/s) and transverse (0.23 +/- 0.07 m/s) repolarization velocities (n = 18). In sheets stretched parallel to the longitudinal axis of surface fibers, AP durations (APDs) increased as a function of fiber length, from the length at zero developed tension to 120% of the length at maximum developed tension (Lmax). Spatial distributions of APDs did not change during stretches along the rising phase of the length-tension curve. In sheets stretched to 50% of Lmax, APDs were shorter and more homogeneous on the endocardium (mean APD, 188 ms; delta APD, 195-186 = 9 ms) than on the epicardium (mean APD, 204 ms; delta APD, 212-186 = 26 ms; n = 8). In guinea pig hearts, activation is rapid; therefore, repolarization depends primarily on intrinsic spatial heterogeneities of APDs. Consequently, repolarization begins at endocardial cells with the shortest APDs and spreads transmurally and then anisotropically on the surface according to the epicardial cell orientation.

Pharmacokinetics and Regional Electrophysiological Effects of Intracoronary Amiodarone Administration

The reason for the delay in onset of the electrophysiological effects and antiarrhythmic efficacy of amiodarone is not clear. The relation between the development of the electrophysiological effects of amiodarone and its myocardial concentration is unknown. We therefore examined the time course of development of electrophysiological effects during intracoronary infusion of amiodarone and related these changes to myocardial concentrations. Amiodarone (0.139 mg/min) or normal saline was infused for 10 hours into the proximal left anterior descending coronary artery of 24 open-chest dogs. Nineteen animals received intracoronary amiodarone and 5 received normal saline (control group). Ten of the 19 that received amiodarone underwent electrophysiological study (amio-EPS group). Sixteen of the 19, including 7 from the amio-EPS group, underwent pharmacological study (PS group). In the amio-EPS group during pacing at a cycle length of 300 ms, changes in conduction velocities in drug-exposed myocardium referenced to nonexposed myocardium at 1 hour of infusion were -3.7% in the longitudinal direction (P = NS) and -7.2% in the transverse direction (P < .05); at 3 hours, -12.9% (P < .05) and -9.1% (P < .05); and at 9 hours, -32.9% (P < .02) and -31.7% (P < .01). These changes were dependent on amiodarone concentration (R2 = .83). There was also an obvious rate-dependent effect that was more pronounced for transverse conduction velocities. This effect was also dependent on amiodarone concentration. In the PS group, amiodarone levels in the drug-exposed myocardium increased from a mean of 5.95 microgram/g at 15 minutes of infusion to 188.88 microgram/g at the 10th hour. This increase was time dependent (R2 = .91). In the nonexposed myocardium, amiodarone levels were always low and increased minimally over time from a mean of 2.68 to 14.45 microgram/g. This increase was also time dependent (R2 = .97). Selective intracoronary amiodarone infusion resulted in selective drug accumulation and concomitant time-dependent reduction of myocardial conduction velocity. There was a significant correlation between the extent of reduction of conduction velocity and myocardial amiodarone concentration but not coronary arterial or systemic concentration. Repolarization was not significantly altered.

Tissue-specific determinants of anisotropic conduction velocity in canine atrial and ventricular myocardium.

Electrical conduction is very rapid and highly anisotropic in atrial fiber bundles, such as the crista terminalis. In contrast to left ventricular myocardium in which the ratio of longitudinal to transverse conduction velocities is approximately 3, propagation velocity in the crista terminalis is approximately 10 times greater in the longitudinal than in the transverse direction. To elucidate potential determinants of these distinct conduction properties, we characterized structural and molecular features of intercellular coupling in the crista terminalis and left ventricular myocardium of the canine heart. Analysis of the number and spatial orientation of myocyte interconnections at gap junctions revealed that a typical left ventricular myocyte was connected to 11.3 +/- 2.2 other myocytes. Approximately equal numbers of connections occurred between ventricular myocytes juxtaposed in side-to-side and end-to-end orientation. In contrast, a typical myocyte of the crista terminalis was connected to only 6.4 +/- 1.7 other cells (P < .05), but nearly 80% of these connections occurred between cells oriented in an end-to-end configuration. In comparison with the ventricular pattern, this spatial distribution of connections would limit intercellular current transfer between laterally apposed cells and thereby enhance anisotropy of conduction velocity in the longitudinal and transverse directions. Ultrastructural analysis showed that crista terminalis myocytes were connected by numerous small gap junctions that occurred in relatively simple, straight intercalated disks. Northern blot analysis showed approximately equivalent amounts of mRNAs encoding the gap junction channel proteins connexin43 and connexin45 but approximately four times more connexin40 mRNA in crista terminalis than in the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute ischemia on anisotropic conduction in canine ventricular muscle.

The effects of acute ischemia on conduction velocities in the longitudinal (theta L) and transverse (theta T) fiber axis were determined from epicardial activation patterns, recorded with 48 bipolar electrodes (plaque electrode, 25 x 35 mm) on the left anterior ventricular wall of eight dogs and the posterior wall of seven dogs. During left ventricular stimulation (cycle length = 300 msec) in the center of the plaque electrode, theta L, theta T, and the ratio of longitudinal to transverse conduction velocities (theta L/T) were measured before and 2 to 5 minutes after occlusion of the left anterior descending coronary artery or the left circumflex coronary artery. During the control state theta L was greater than theta T demonstrating anisotropic properties of cardiac muscle, not only in the anterior but also in the posterior wall. During acute ischemia theta L and theta T were decreased from the control value and theta T was decreased by a greater extent than theta L resulting in an increase in theta L/T from 1.83 +/- 0.31 (mean +/- SD) to 2.19 +/- 0.36 in the anterior wall and from 1.58 +/- 0.17 to 1.92 +/- 0.28 in the posterior wall. During ventricular fibrillation some lines of conduction block were parallel to the long axis of epicardial muscle fiber bundle and the others were perpendicular. In conclusion, acute ischemia increased anisotropic conduction (theta L/T) in the epicardial ventricular muscle mainly due to greater reduction in theta T, in the anterior and the posterior wall. This augmented anisotropic ventricular conduction may have some relation to the initiation of ventricular fibrillation during acute ischemia.

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

Myocardial propagation may contribute to fatal arrhythmias in patients with idiopathic dilated cardiomyopathy (IDC). We examined this property in 15 patients with IDC undergoing cardiac transplantation and in 14 control subjects. An 8 x 8 array with electrodes 2 mm apart was used to determine the electrical activation sequence over a small region of the left ventricular surface. Tissue from the area beneath the electrode array was examined in the patients with IDC. The patients with IDC could be divided into three groups. Group I (n = 7) had activation patterns and estimates of longitudinal (theta L = 0.84 +/- 0.09 m/s) and transverse (theta T = 0.23 +/- 0.05 m/s) conduction velocities that were no different from controls (theta L = 0.80 +/- 0.08 m/s, theta T = 0.23 +/- 0.03 m/s). Group II (n = 4) had fractionated electrograms and disturbed transverse conduction with normal longitudinal activation, features characteristic of nonuniform anisotropic properties. Two of the control patients also had this pattern. Group III (n = 4) had fractionated potentials and severely disturbed transverse and longitudinal propagation. The amount of myocardial fibrosis correlated with the severity of abnormal propagation. We conclude that (a) severe contractile dysfunction is not necessarily accompanied by changes in propagation, and (b) nonuniform anisotropic propagation is present in a large proportion of patients with IDC and could underlie ventricular arrhythmias in this disorder.

Electrophysiologic and Arrhythmogenic Effects of Bupivacaine

It has been shown that administration of toxic doses of bupivacaine may induce ventricular dysrhythmias. However, the mechanism of these dysrhythmias is still unknown. The present study was designed to test the hypothesis that bupivacaine facilitates the occurrence of reentrant ventricular dysrhythmias. High-resolution ventricular epicardial mapping was used to study the effects of 0.2, 0.5, 1.0, and 5.0 micrograms/ml bupivacaine in 11 Langendorff-perfused rabbit hearts. Five hearts were kept intact (intact heart). In six other hearts, a thin layer of epicardium was obtained by an endocardial cryotechnique (frozen heart). Bupivacaine induced ventricular dysrhythmias in 3 of 5 intact hearts at 5.0 micrograms/ml. In 3 of 6 frozen hearts, 0.2 micrograms/ml bupivacaine facilitated the induction of ventricular tachycardia by programmed electrical stimulation. Epicardial mapping showed that all tachycardias were based on reentry of the impulse around an arc of functional conduction block. Moreover, bupivacaine significantly prolonged the ventricular effective refractory period and slowed longitudinal and transverse conduction velocity in a dose- and use-dependent manner. It is concluded that bupivacaine facilitates induction of reentrant ventricular dysrhythmias in isolated rabbit heart.

Suppression of longitudinal versus transverse conduction by sodium channel block. Effects of sodium bolus.

Arrhythmias resulting from treatment with sodium channel-blocking antiarrhythmic drugs have been successfully treated with sodium infusion, although the mechanism underlying this effect is uncertain. In this study, we used a multielectrode array to examine the effects of O-desmethyl encainide (ODE), a potent sodium channel-blocking metabolite of encainide, on conduction in canine ventricle. ODE depressed both longitudinal and transverse conduction velocities in a plasma concentration-related fashion (r = -0.74, -0.60; p less than 0.001). At ODE concentrations less than or equal to 300 ng/ml (n = 34), conduction velocity was depressed to the same extent in the longitudinal (-21.9 +/- 8.4%, SD) and transverse orientations (-22.0 +/- 8.8%). However, at concentrations greater than 300 ng/ml (n = 17), conduction was significantly more impaired longitudinally than transversely (-44.5 +/- 11.7% versus -34.4 +/- 13.7%, p less than 0.02). In 12 animals with high concentrations (mean, 432 +/- 32 ng/ml), a 5-meq/kg bolus of sodium chloride over 1 minute immediately increased conduction velocity; this effect was significantly greater and longer lasting in the longitudinal orientation. In two animals, conduction block in the longitudinal orientation was documented at high plasma ODE and was immediately reversed by sodium bolus. We conclude that the major effect of sodium in animals with excess sodium channel block is improvement of longitudinal propagation; this effect may underlie the antiarrhythmic action of sodium in the analogous clinical setting.

Electrophysiologic Changes and Ventricular Fibrillation in Acute Regional Ischemia in the Porcine Heart: The Concept of Wavelength

Early Electrophysiologic Changes in Acute Ischemia. Introduction: The purpose of this study was to match changes in conduction velocity, refractoriness, and wavelength during acute regional ischemia with initiation of ventricular fibrillation. Methods and Results: In 30 isolated, Langendorff‐perfused pig hearts we measured refractory period duration and conduction velocity in ventricular myocardium during the first minutes of regional ischemia in an attempt to determine the minimal changes in these parameters related to the occurrence of ventricular fibrillation (VF). In addition, we wanted to evaluate whether wavelength, i.e., the product of conduction velocity and refractory period, was a useful parameter to predict the occurrence of arrhythmias, as has been shown to be the case for atrial arrhythmias.1 The refractory period increased significantly after 1 minute of ischemia at basic cycle length and after one and two premature beats. Longitudinal and transverse conduction velocities varied with ischemic time. Compared to the preocclusion value, the longitudinal conduction velocity decreased significantly, but only after 2 minutes of ischemia and at basic cycle length. Wavelength was the least sensitive parameter for ischemia: neither in the longitudinal nor in the transverse direction did it change significantly even during 5 minutes of ischemia. VF was never induced by applying a single premature stimulus within the ischemic area. It occurred in 33% of the occlusions when three successive premature stimuli were delivered from within the ischemic zone, and in 100% when they were applied to the nonischemic myocardium. Whenever fibrillation was induced, it occurred within 3 minutes following coronary occlusions. Wavelength, neither before nor after coronary occlusion, could predict whether VF would occur. The only difference between hearts that fibrillated by stimulation of the ischemic myocardium and those that did not was that, in the first group, the refractory period at the site of stimulation prolonged significantly less than in the no‐VF group. Since electrophysiologic changes within the ischemic zone are inhomogeneous,2 an attempt was made to measure simultaneously at 52 sites the onset of inhomogeneity by determining the average interval between local depolarization during VF. This so‐called VF interval is an index of local refractoriness.3 The coefficient of variation of the VF interval, taken as an index of spatial dispersion in refractoriness, increased significantly 1 minute after occlusion in the border zone and 2 minutes after occlusion in the central ischemic area. Conclusion: In conclusion, wavelength is not a useful parameter to predict the occurrence of VF in hearts with regional ischemia because of the inhomogeneity in refractoriness, which develops within 2 minutes of ischemia. VF occurs when hearts are stimulated from sites with relatively short refractory periods, either within or outside the ischemic zone. (J Cardiovasc Electrophysiol, Vol. 3, pp. 128–140, April 1992)

The Effects of K+ on Anisotropic Conduction in Sheets of Perfused Rabbit Ventricular Epicardium

Potassium and Anisotropy. Introduction: The purpose of this study was to investigate the effects of potassium on anisotropic conduction in rabbit ventricles. Methods and Results: In Langendorff perfused rabbit hearts, a two‐dimensional epicardial layer of anisotropic myocardium was created by cryodestruction of the endocardial four fifths of the left ventricle. The heart was paced at 0.5 Hz and the epicardial spread of activation was recorded with a high‐resolution mapping electrode (240 points). In ten experiments, we studied the effects of stepwise increased concentrations of extracellular potassium on epicardial conduction, longitudinal and transverse to the fiber direction. At 6.2 mM of K+, longitudinal conduction velocity (θL) was 61 ± 6.2 and transverse conduction velocity (θT) 25 ± 4.6 cm/sec with a ratio θL/θT of 2.6. At a high concentration of 12.5 ± 1.1 mM, conduction slowed down to 29 ± 6.0 and 11 ± 4.4 cm/sec, respectively, with a slightly increased ratio of 3.2 (NS). The amount of depression of θL and θT varied considerably from experiment to experiment and from region to region. On the average, no statistical difference in the depression of conduction velocity in relation to the fiber orientation was found. At K + concentrations of more than 12.5 ± 1.1 mM, local conduction was seriously impaired at various sites. Lines of functional conduction block appeared in longitudinal and transverse direction. Conclusion: We conclude that during slow heart rates, depression of the fast sodium channels by high extracellular K + causes no detectable differential effects on conduction velocity or on occurrence of conduction block, longitudinal or transverse to the general fiber orientation.

Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium.

The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation. In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration [( K+]o) and heptanol were studied. [K+]o and heptanol each had a dose-dependent effect on VT cycle length. However, high [K+]o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high [K+]o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean [K+]o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high [K+]o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high [K+]o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block. During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high [K+]o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation.

Structure of canine Bachmann's bundle related to propagation of excitation.

Impulse propagation and histology were studied in adult and neonatal canine Bachmann's bundle. Both showed nonuniform electrical anisotropy: effective longitudinal conduction velocity (theta L) markedly exceeded effective transverse conduction velocity (theta T), and extracellular potential waveforms with transverse propagation were polyphasic. An age difference in theta L (0.80 m/s neonate, 1.31 m/s adult) was found; it could be largely accounted for by a difference in myocyte diameter (4.7 microns neonate, 17.1 microns adult). Close apposition of myocytes in the neonate and development of transverse tubules in the adult may have influenced theta L at each stage. Perimysial septa separated fascicles in both neonatal and adult bundles; however, endomysial septa between individual myocytes were completely developed only in adult bundles. Thus perimysial septa were much more responsible for nonuniform anisotropy and low theta T than endomysial septa. Fascicle diameter and length were greater in the adult, which may have affected transverse propagation. Specialized conduction system cells could not be identified.

Effects of cellular uncoupling on conduction in anisotropic canine ventricular myocardium.

Experiments were performed on canine superfused ventricular epicardial tissue slices to determine the effects of 1.0-2.0 mM heptanol, an uncoupling agent, on conduction longitudinal and transverse to myocardial fiber orientation. Conduction velocities were measured between proximal and distal pairs of epicardial electrodes oriented transverse and longitudinal to the direction of a conducted wavefront evoked by pacing at a basic cycle length of 2,000 msec from one margin of the tissue before and after the addition of heptanol. In a separate group of tissues, the dual bipolar orthogonal electrode was used to sequentially map epicardial activation at 40 to 45 sites in a 1 cm x 2 cm area before and 30 minutes after the introduction of heptanol. In a third group of tissues, transmembrane potentials were recorded with standard microelectrode techniques to determine the effects of heptanol on action potential characteristics. Heptanol did not significantly effect action potential amplitude or maximum rate of depolarization. After 1.0 mM heptanol, conduction velocity began to decrease in 1-2 minutes and reached a steady state in 15-20 minutes. Conduction velocity in the longitudinal direction decreased from a control value of 0.56 +/- 0.13 to 0.46 +/- 0.10 M/sec (+/- SD) at 30 minutes after heptanol (p = 0.005). In the transverse direction, it decreased from 0.24 +/- 0.09 to 0.17 +/- 0.05 M/sec (p = 0.002). The ratio of longitudinal to transverse conduction velocities increased from 2.54 +/- 1.00 to 2.94 +/- 0.82 (p = 0.042). Thus, heptanol preferentially slowed conduction in the transverse direction. Because heptanol did not greatly influence active membrane properties, we used cable equations to calculate the time course of the change in effective junctional resistivity, which rose from 133.2 omega.cm before heptanol to 312.2 omega.cm 30 minutes after heptanol administration. We conclude that heptanol slows conduction velocity by selectively increasing junctional resistivity. The preferential slowing of conduction in the transverse direction is most likely due to the fact that more junctional resistances are encountered per unit distance in the transverse than in the longitudinal direction.

The effects of procainamide on conduction in anisotropic canine ventricular myocardium.

Although conduction velocity in cardiac tissue is dependent on fiber orientation, the influence of commonly used antiarrhythmic agents on conduction longitudinal and transverse to such fibers is unknown. We evaluated the effects of procainamide on conduction velocity and intracellular potentials in vitro during conduction longitudinal and transverse to fiber orientation in epicardial strips obtained from areas of uniform fiber orientation from 15 adult mongrel dogs. Ventricular epicardial strips demonstrated marked anisotropy. At a pacing cycle length of 1000 msec, mean conduction velocity longitudinal to fiber orientation averaged 0.602 +/- 0.051 m/sec and mean conduction velocity transverse to fiber orientation was 0.186 +/- 0.024 m/sec, resulting in a ratio of longitudinal to transverse conduction velocities of (theta L/T) 3.27 +/- 0.38. After the addition of procainamide, conduction velocity decreased to 0.532 +/- 0.062 m/sec longitudinal to fiber orientation and to 0.174 +/- 0.023 m/sec transverse to fiber orientation resulting in a decrease of theta L/T to 3.09 +/- 0.37 (p less than .05 vs control). Before the addition of procainamide, when pacing at progressively shorter cycle lengths, conduction velocity longitudinal to fiber orientation was relatively unchanged, whereas conduction velocity transverse to fiber orientation decreased resulting in an increase in theta L/T. After the addition of procainamide, conduction velocity at shorter pacing cycle lengths decreased both longitudinal and transverse to fiber orientation demonstrating the well-known use-dependent effect of procainamide. However, in contrast to control conditions, conduction velocity longitudinal to fiber orientation was slowed by a greater extent than the conduction transverse to fiber orientation, resulting in an even greater decrease in theta L/T. To investigate the effect of differences in drug binding during propagation in different directions, we examined conduction velocity during alternations in pacing direction and compared it with velocity during steady-state pacing. At a pacing cycle length of 1000 msec, no difference was observed between the initial conduction velocity after changing pacing directions and the steady-state conduction velocity. At pacing cycle lengths shorter than 1000 msec, when changing from transverse to longitudinal conduction, there was an initial drop in normalized conduction velocity that was present on the first beat of longitudinal conduction; however, with continued pacing in a longitudinal direction there was a further decrease in conduction velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age.

Elucidation of the mechanisms of cardiac conduction disturbances leading to reentry will require resolution of the details of multidimensional propagation at a microscopic size scale (less than 200 micron). In practice, this will necessitate the combined analysis of extracellular and transmembrane action potentials. The purpose of this paper is to demonstrate the relationships between the time derivatives of the extracellular waveforms and the underlying action potentials in the experimental analysis of anisotropic propagation at this small size scale, and apply these relationships to human atrial muscle at different ages. The extracellular waveforms and their derivatives changed from a smooth contour during transverse propagation in young preparations to complex polyphasic waveforms in the older preparations. The major problem was to estimate the size and location of small groups of fibers that generated the complex waveforms in the older preparations. We found dissimilarities in the derivatives that distinguished source (bundle) size from the distance of the source to the measurement site. The differences in the extracellular waveforms and their derivatives indicated that there was electrical uncoupling of the side-to-side connections between small groups of fibers with aging. These changes produced a prominent zigzag course of transverse propagation at a microscopic level which, in turn, accounted for the increased complexity of the waveforms. The waveform differences also correlated with the development of extensive collagenous septa that separated small groups of fibers. The electrophysiological consequence was an age-related decrease in the "effective" transverse conduction velocities to the range of the very slow conduction (less than 0.08 m/sec) which makes it possible for reentry to occur in small regions of cardiac muscle with normal cellular electrophysiological properties.

Directional differences of impulse spread in trabecular muscle from mammalian heart.

Trabecular bundles from the right ventricle of calf hearts were used. Electrical properties measured by the application of longitudinal current were compared to those measured by the application of transverse current. 2. The following data were obtained on the basis of classical cable analysis: (i) a ratio of 3-0 for longitudinal to transverse conduction velocity, (ii) a ratio of 3-6 for intra- to extracellular longitudinal resistance, (iii) a ratio of 12-6 for intra- to extracellular transverse resistance, (iv) a ratio of 9-4 for intracellular transverse to intracellular longitudinal resistance, (v) a ratio of 2-7 for the extracellular transverse to the extracellular longitudinal resistance. 3. The disparity in conduction velocity could be explained on the sole grounds of differences in the resistivity of the intracellular and extracellular paths for current flow in the two directions, confirming theoretical predictions. 4. The value of the transverse internal resistance can be accounted for on the ground of frequent branching in a three-dimensional network. There is no need to make the additional assumption of current flow through lateral low resistance pathways between parallel fibres.