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[Influence of Carbocromen on A-V-conduction and refractory period. Electrophysiological study with His-bundle-electrography in experimental animals (author's transl)].

The influence of 3-(2-diethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydr ochloride (carbocromen, Intensaïn) on A-V-conduction and refractory period was studied by means of His-bundle-electrography on 12 anaesthetized cats. Immediately after application of carbocromen 6 mg/kg the A-H-conduction time was increased. In contrast to this, 12 mg/kg carbocromen caused significant prolongation of H-v interval. This study shows that carbocromen has effects on intraventricular conduction.

Animals↗

Time dependence of ventricular refractory periods: implications for electrophysiologic protocols.

Cardiac refractory periods are routinely measured during electrophysiologic testing. Informal observations suggested that the effective refractory period lengthened with a prolongation of the time in sinus rhythm (basic cycle length time) between successive runs of drive stimuli (S1S1s). If this were true, failure to control the basic cycle length time could affect the results and interpretation of electrophysiologic testing. To study this phenomenon, the effective refractory period was studied in 20 patients during sinus rhythm and two ventricular paced rates with up to three extrastimuli, while varying the basic cycle length time from 2 to 3, to 10 to 20 s. With each of the stimulation sequences used, the effective refractory period lengthened as the basic cycle length time increased ("basic cycle length time-effective refractory period effect"). The effect was most pronounced when extrastimuli were used during the two ventricular paced rates. As the basic cycle length time increased from 2 to 3 to 20 s, the mean effective refractory period determined during sinus rhythm increased from 296 to 300 ms; with the first ventricular paced rate, the effective refractory period increased from 259 to 272 ms (p less than 0.0003) and with the second ventricular paced rate, the effective refractory period increased from 250 to 263 ms (p less than 0.01). The basic cycle length time-effective refractory period effect became more pronounced as the number of extrastimuli increased. With the second ventricular paced rate, as basic cycle length was increased from 2 to 3 to 20 s, the mean prolongation in the cumulative effective refractory period (S1 to final extrastimulus) as the number of extrastimuli increased from 1 to 2 to 3, was 13 (p less than 0.01), 42 (p less than 0.0003) and 82 ms (p less than 0.001), respectively. Results were confirmed in 17 instances by redetermining the effective refractory period at the 2 to 3 s basic cycle length time after the final 20 s basic cycle length time determination, and demonstrating that it was similar to the effective refractory period after the initial 2 to 3 s basic cycle length time. No further prolongation of the effective refractory period could be demonstrated by increasing basic cycle length time from 20 to 60 s, and no significant effect of medications on the basic cycle length time-effective refractory period effect could be demonstrated.

Adolescent↗

Effect of disopyramide on initiation of atrial fibrillation and relation to effective refractory period.

Electrophysiologic studies were performed before and after intravenous administration of disopyramide (2 mg/kg) to 40 patients with either documented or suspected atrial fibrillation (AF). In control studies, sustained AF (greater than 1 minute), nonsustained AF (1 to 60 seconds) and no AF were found in 14, 18 and 8 patients, respectively. After disopyramide, the ability to initiate AF was totally lost in 18 patients (group A), while 22 patients (group B) showed sustained AF (11 patients) or nonsustained AF (11 patients). The effective refractory period of the atrium was 232 +/- 41 ms in the control study and 266 +/- 49 ms after disopyramide. Atrial functional refractory periods before and after disopyramide were 282 +/- 43 and 317 +/- 48 ms, respectively. The differences and ratios of the refractory periods after and before disopyramide were higher in group A than in group B (p less than 0.001). The prolongation of atrial refractoriness after disopyramide was important to suppress the initiation of AF in group A. In some group B patients, on the other hand, the initiation of AF was promoted after disopyramide. Disopyramide may alter the atrial electrophysiologic substrate required for AF initiation.

Atrial Fibrillation↗

Recovery cycles of event-related potentials in multiple detection tasks.

We examined the recovery cycle of the P3 in two different experiments, one in which subjects detected near-threshold (NT) tones and the other in which they detected suprathreshold (ST) tones presented in rapid sucession. In both experiments P3 amplitudes and latencies were decremented at ISIs of 300 msec but fully recovered by 900 msec. The N1 and P2 components elicited by ST tones showed a much more prolonged (> 7.0 sec recovery cycle. These results reveal that the P3 has a recovery cycle which closely resembles that of human decision processes, a recovery cycle far shorter than those of exogenous ERP components previously examined. Sequential changes in P3 amplitude between trials were also investigated. In both experiments P3 amplitudes were largest following signal-absent trials. This suggests that subjects may have modified their expectancies about tone delivery on a trial-by-trial basis. In these experiments the P3 wave was distinguished from the resolution of the CNV on several grounds, including differences in scalp distribution, intra-trial kinetics, effect of previous tone sequences, and distributions among the subjects. These results support the position that P3 is a neurophysiological event distinct from modulations of the CNV. Differences in the amplitude and habituation of P3s produced in the NT and ST experiments suggest that the P3 may be related to decisions which require 'controlled' stimulus processing.

Auditory Threshold↗

Psychophysics of electrical stimulation of striate cortex in macaques.

Macaques indicated their detection of onset or alteration of 0.2-ms pulses applied in various configurations through electrodes implanted in striate cortex. When microelectrodes were introduced and left in place, the threshold for detection of 100-Hz pulses nearly doubled within 24 h. However, for chronically implanted platinum-alloy macroelectrodes detection thresholds usually remained stable for many months, independently of location within striate cortex or its immediately subjacent white matter. Thresholds were unaffected by the visual conditions, such as light versus darkness, or movement of the eyes; but in one animal blind after acute glaucoma thresholds for loci in striate cortex were permanently decreased by about 50%. Learning to respond to electrical stimulation of the optic tract produced no tendency to respond to such stimulation of striate cortex. Onset of stimulation at a given locus could be detected even in the face of continuous supraliminal stimulation at four surrounding loci on a 3-mm radius. The surround stimulation did alter the threshold of the central locus, but such stimuli could not summate if they were subliminal by some 10%. Cessation of stimulation that had been continuing for 1 min to 1 h could be detected if it were being applied at a level 20-75% above that needed for detection of stimulus onset. Continuous stimulation had a pronounced "priming" effect, in that modulation of frequency or intensity of such stimulation by as little as 5% could be detected (e.g., 20 microA in a background of 500 microA, or <2-ms interpulse interval with pulses at 50 Hz). Using pulses inserted in various phase relations to ongoing pulses at 2-5 Hz, it could be determined that stimulus pulses were surrounded by a strong facilitatory period for about 30 ms, which was then replaced by refractoriness. Given the congruence of macaque and human visual anatomy and psychophysics, these results further encourage efforts to develop a cortical prosthesis for the blind.

Animals↗

Laminar variation in threshold for detection of electrical excitation of striate cortex by macaques.

Macaques were trained to signal their detection of electrical stimulation applied by a movable microelectrode to perifoveal striate cortex. Trains of < or =100 cathodal, 0.2-ms, constant current pulses were delivered at 50 or 100 Hz. The minimum current that could be reliably detected was measured at successive depths along radial electrode penetrations through the cortex. The lowest detection thresholds were routinely encountered when the stimulation was applied to layer 3, particularly just at the juncture between layers 3 and 4A. On the average, there was a twofold variation in threshold along the penetrations, with the highest intracortical thresholds being in layers 4C and 6. Variations as high as 20-fold were obtained in some individual penetrations, whereas relatively little change was observed in others. The minimum detectable current was 1 muA at a site in layer 3, i.e., 10-100 times lower than that for surface stimulation. Because macaques, as do human subjects, find electrical stimulation of striate cortex to be highly similar at all loci (a phosphene in the human case), it is puzzling as to how such uniformity of effect evolves from the exceedingly intricate circuitry available to the effective stimuli. It is hypothesized that the stimulus captures the most excitable elements, which then suppress other functional moieties, producing only the luminance of the phosphene. Lowest thresholds presumably are encountered when the electrode lies among these excitable elements that can, with higher currents, be stimulated directly from some distance or indirectly by the horizontal bands of myelinated axons, the stria of Baillarger.

Animals↗

Fundamental electrophysiologic investigation of spinal cord: refractory period of feline conductive spinal cord evoked potential.

Refractory periods and recovery curves have been used to investigate the physiologic importance and disturbance of peripheral nerves, but the refractory periods of the central nervous system (CNS) have seldom been investigated. We estimated the refractory periods and the recovery curves of the ascending and descending conductive spinal cord evoked potentials (SCEP) in cats. The absolute refractory period of the first and second potentials of both the ascending and descending SCEP was approximately 0.4-0.5 ms. The amplitudes of the first potentials of the ascending and descending SCEP elicited by test stimuli exhibited significant differences, but their latencies did not differ significantly except at the interstimulus interval (ISI) of 1.5 ms, which implies that the same type of fibers was stimulated in the first potentials of the ascending and descending SCEP. The second potential of the descending SCEP elicited by test stimulus showed > 100% amplitude and a maximal recovery of 200% when the ISI was 3.0 ms. The third potential was produced in the test response more easily when a lower vertebral level (L4) was used as the recording site and the ISI was between 1.0 and 4.0 ms. We consider these phenomena to be the result of elimination of the synaptic inhibitory influence by the conditioning stimulus of the paired stimuli for the descending SCEP.

Action Potentials↗

Impulse encoding across the dendritic morphologies of retinal ganglion cells.

Nerve impulse entrainment and other excitation and passive phenomena are analyzed for a morphologically diverse and exhaustive data set (n = 57) of realistic (3-dimensional computer traced) soma-dendritic tree structures of ganglion cells in the tiger salamander (Ambystoma tigrinum) retina. The neurons, including axon and an anatomically specialized thin axonal segment that is observed in every ganglion cell, were supplied with five voltage- or ligand-gated ion channels (plus leakage), which were distributed in accordance with those found in a recent study that employed an equivalent dendritic cylinder. A wide variety of impulse-entrainment responses was observed, including regular low-frequency firing, impulse doublets, and more complex patterns involving impulse propagation failures (or aborted spikes) within the encoder region, all of which have been observed experimentally. The impulse-frequency response curves of the cells fell into three groups called FAST, MEDIUM, and SLOW in approximate proportion as seen experimentally. In addition to these, a new group was found among the traced cells that exhibited an impulse-frequency response twice that of the FAST category. The total amount of soma-dendritic surface area exhibited by a given cell is decisive in determining its electrophysiological classification. On the other hand, we found only a weak correlation between the electrophysiological group and the morphological classification of a given cell, which is based on the complexity of dendritic branching and the physical reach or "receptive field" area of the cell. Dendritic morphology determines discharge patterns to dendritic (synaptic) stimulation. Orthodromic impulses can be initiated on the axon hillock, the thin axonal segment, the soma, or even the proximal axon beyond the thin segment, depending on stimulus magnitude, soma-dendritic membrane area, channel distribution, and state within the repetitive impulse cycle. Although a sufficiently high dendritic Na-channel density can lead to dendritic impulse initiation, this does not occur with our "standard" channel densities and is not seen experimentally. Even so, impulses initiated elsewhere do invade all except very thin dendritic processes. Impulse-encoding irregularities increase when channel conductances are reduced in the encoder region, and the F/I properties of the cells are a strong function of the calcium- and Ca-activated K-channel densities. Use of equivalent dendritic cylinders requires more soma-dendritic surface area than real dendritic trees, and the source of the discrepancy is discussed.

Action Potentials↗

Forebrain neurons driven by rewarding stimulation of the medial forebrain bundle in the rat: comparison of psychophysical and electrophysiological estimates of refractory periods.

Psychophysically derived estimates of recovery from refractoriness were obtained at self-stimulation sites in the lateral hypothalamus and ventral tegmental area. The refractory periods of single units driven by the same stimulation electrodes and stimulation fields were then measured electrophysiologically. Antidromically driven units with refractory periods longer than those of the neurons responsible for the rewarding effect were concentrated in the septal complex. Units with refractory periods that overlapped the estimates for the reward-related neurons were found in this region as well but were also encountered in neighboring structures lateral, ventral, and/or caudal to the septal nuclei. It is argued that this latter class of units should be considered as possible constituents of the directly stimulated substrate for the rewarding effect because they are driven by rewarding stimulation, have refractory periods similar to those of the reward-related neurons and arise in or near regions in which lesions have been effective in decreasing the rewarding effect of stimulating the medial forebrain bundle.

Animals↗

Atrioventricular node reentrant tachycardia in patients with a long fast pathway effective refractory period: clinical features, electrophysiologic characteristics, and results of radiofrequency ablation.

Twenty-two patients (group 1) with AV node reentrant tachycardia and a baseline fast pathway effective refractory period (ERP) > or = 500 msec were compared with 30 consecutive patients (group 2) with AV node reentrant tachycardia and a fast pathway ERP < 500 msec. Both groups underwent slow pathway ablation. In the patients with complete elimination of slow pathway, the fast pathway ERP and shortest 1:1 conduction cycle length shortened significantly after ablation but was greater in group 1 (n = 14) than in group 2 (n = 21) (125 +/- 78 msec vs 48 +/- 29 msec, p < 0.001 and 103 +/- 72 msec vs 52 +/- 30 msec, p < 0.001, respectively). In group 1, the shortening of fast pathway ERP was correlated to baseline difference between anterograde fast and anterograde slow ERP (r = 0.806, p < 0.001, slope = 1.08), and the shortening of fast pathway shortest 1:1 conduction cycle length was correlated to baseline difference between anterograde fast and anterograde slow shortest 1:1 conduction cycle length (r = 0.885, p < 0.001, slope = 1.47). During follow-up bradycardia did not develop in any patient and no one required pacing. This shortening of the fast pathway ERP and shortest 1:1 conduction cycle length after complete elimination of slow pathway reduced the concern of subsequent impairment of AV node conduction.

Adrenergic beta-Agonists↗

Neuron function inferred from behavioral and electrophysiological extimates of refractory period.

The refrcactory period of neurons mediating an electrically elicited behavior (self-stimulation) was estimated by varying the intrapair pulse separation in a stimulating train made up of pulse pairs and measuring the intensity of the elicited behavior. Two neuronal systems with different refractory periods were indicated. Single-unit recording in acute preparations stimulated through self-stimulation electrodes revealed primarily two classes of units. Each class gave refractory period estimates characteristic of one of the behaviorally indicated systems. The experiments illustrate a technique for establishing functional relations between single units in the brain and gross behavior.

Action Potentials↗

Effect of sudden rate acceleration on the human His-Purkinje system: adaptation of refractoriness in a dampened oscillatory pattern.

Although the refractoriness of the human His-Purkinje system (HPS) during constant-cycle length pacing appears to be closely related to the cycle length of the stimulation, the mode of adaptation of this refractoriness with sudden rate acceleration is not well understood. A systematic evaluation of this adaptation was performed in 14 patients with normal QRS durations and HV intervals referred for electrophysiologic evaluation. The relative refractory period of the HPS (HPS-RRP) was evaluated by the extrastimulus (S2) method during a constant ventricular drive (S1) having a cycle length as close to sinus rhythm as possible. An accelerated train of 6 ventricular beats (S1') was then added to the constant drive and the HPS-RRP of each successive beat of this train was similarly determined. Mean S1 cycle length was 750 +/- 164 msec (range 600 to 1000). Mean S1' cycle length was 475 +/- 55 msec (range 400 to 600). The HPS-RRP of each successive beat of the accelerated train was significantly shorter than that during the S1 drive and behaved in a dampened oscillatory fashion alternating from a lower value on the odd-numbered beats to a higher value on the even-numbered beats. In contrast, the effective and relative refractory periods of the ventricular myocardium during the accelerated train behaved in a cumulative manner, decreasing progressively with the first 2 beats of the train before reaching a plateau value. In conclusion, the data reported here present a new and intriguing picture of the mode of adaptation of the HPS refractoriness to sudden rate acceleration. At least in the range of the cycle lengths used in this study, the refractoriness of the HPS behaves in a dampened oscillatory manner that is radically different from the behavior of the ventricular myocardial refractoriness.

Adaptation, Physiological↗

Effects of thoracic epidural anesthesia with and without autonomic nervous system blockade on cardiac monophasic action potentials and effective refractoriness in awake dogs.

BACKGROUND: The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. METHODS: The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. RESULTS: Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. CONCLUSIONS: This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

Action Potentials↗