Effects of spatial dispersion of acetylcholine release on AV conduction responses to vagal stimulation in dogs

1991 ◽  
Vol 261 (2) ◽  
pp. H392-H397 ◽  
Author(s):  
T. N. Yang ◽  
J. Cheng ◽  
P. Martin ◽  
M. N. Levy
Keyword(s):  
Cardiac Cycle ◽  
Spatial Dispersion ◽  
Vagal Stimulation ◽  
Nerve Fibers ◽  
Vagal Nerve ◽  
Conduction Time ◽  
Vagal Activity ◽  
Ach Release ◽  
Response Curves ◽  
Av Conduction

We determined the effects on atrioventricular (AV) conduction of changing the spatial dispersion of acetylcholine (ACh) release from vagal nerve fibers in anesthetized dogs. We paced the atria at a constant rate and stimulated the vagus nerves with one stimulus burst per cardiac cycle. We varied the spatial heterogeneity of ACh release in the cardiac tissues by changing the stimulus voltage, and we varied the quantity of ACh release from each excited nerve fiber by changing the number of pulses per stimulus burst. We slightly changed the stimulus timing with each heartbeat to scan the entire cardiac cycle. We constructed phase-response curves (PRCs) by plotting the changes in AV conduction time as a function of the timing of vagal stimulation. We found that the amplitude of the PRC varied directly with average AV conduction time (AV), whereas the minimum-to-maximum phase difference of the PRC varied inversely with AV. However, for any given change in AV, the specific characteristics of the PRCs did not depend on whether we varied the number of pulses per burst or the stimulus voltage. Therefore, the phase-dependent characteristics of the dromotropic responses appear to be unaffected by the spatial dispersion of ACh release from the vagal nerve endings. The effects of vagal activity on the AV conduction time are determined by those conducting fibers that are the least restrained by neurally released ACh.

Synchronization of automatic cells in S-A node during vagal stimulation in dogs

1984 ◽  
Vol 246 (4) ◽  
pp. H585-H591 ◽  
Author(s):  
T. Yang ◽  
M. D. Jacobstein ◽  
M. N. Levy
Keyword(s):  
Response Curve ◽  
Cardiac Cycle ◽  
Phase Response Curve ◽  
Vagal Stimulation ◽  
Nerve Fibers ◽  
Phase Response ◽  
Vagal Activity ◽  
Maximum Phase ◽  
The Right ◽  
Phase Differences

In anesthetized, open-chest dogs, one burst of stimuli was delivered to the left or right vagus nerve each cardiac cycle. The timing of the stimulus bursts relative to the cardiac cycle was varied by a constant, small amount on successive cardiac cycles, until the entire cardiac cycle was scanned. The level of vagal activity was changed by varying the number of stimulus pulses in each burst; two levels of activity were used in each experiment. For a given level of vagal activity, the mean cardiac cycle length and the amplitude of the phase-response curve were significantly greater during right than during left vagal stimulation. These response characteristics increased as the level of vagal activity was augmented. The minimum-to-maximum phase differences of the phase-response curve were less during right than during left vagal stimulation and when the level of vagal activity was increased. The disparities between the minimum-to-maximum phase differences for the right and left vagi are probably ascribable to the associated differences in the overall magnitudes of the chronotropic responses, rather than to any fundamental difference in the innervation of the effector cells by nerve fibers originating from the right and left sides.

Phasic influences of vagal stimulation on atrioventricular conduction

1988 ◽  
Vol 66 (9) ◽  
pp. 1198-1205 ◽  
Author(s):  
Margaret R. Warner ◽  
Jerod M. Loeb
Keyword(s):  
Sympathetic Activity ◽  
Cycle Length ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Response Patterns ◽  
Constant Frequency ◽  
Stimulus Interval ◽  
Av Conduction ◽  
Anesthetized Dogs ◽  
Interval Response

The beat-by-beat changes in atrioventricular (AV) conduction evoked by constant frequency and phase-coupled vagal stimulation were examined both qualitatively and quantitatively in 13 anesthetized dogs. The effects of pacing cycle length and sympathetic activity on the vagally induced phasic changes in AV conduction were also characterized. When the vagal stimulus interval was nearly equal to the pacing cycle length and the vagal stimulus moved progressively through the cardiac cycle, AV interval oscillated in a rhythmic fashion. The rhythmicity of the vagally induced AV interval oscillations was altered substantially by changes in either the vagal stimulus interval or the pacing cycle length. The vagally induced AV interval oscillations were abolished during phase-coupled vagal stimulation; however, the magnitude of the resultant steady-state AV interval depended on the time relative to the phase of the cardiac cycle that the vagal stimulus was delivered. In the presence or absence of sympathetic stimulation, a vagal stimulus falling approximately 200 ms prior to atrial depolarization evoked the greatest prolongation in AV interval, regardless of the pacing cycle length. Additionally, the effects of combined sympathetic and phase-dependent vagal stimulation on the AV interval were additive. These data confirm that the influence of a vagal stimulus on AV interval can be predicted from the phase in the cardiac cycle that the vagal stimulus is delivered. Moreover, this phase dependency of vagal effects evokes marked qualitative variations in AV interval response patterns when either the vagal stimulus interval or the pacing cycle length is altered.

Effect of phasic vagal stimulation and atrial pacing site on atrioventricular conduction time

1997 ◽  
Vol 272 (5) ◽  
pp. H2289-H2298 ◽  
Author(s):  
D. A. Igel ◽  
D. W. Wallick ◽  
P. J. Martin ◽  
M. N. Levy
Keyword(s):  
Coronary Sinus ◽  
Cycle Length ◽  
Vagal Stimulation ◽  
Interatrial Septum ◽  
Conduction Time ◽  
Atrial Pacing ◽  
Av Conduction ◽  
Recovery Times ◽  
Anesthetized Dogs ◽  
The Right

We tested the hypothesis that the effect of phasic vagal stimulation on atrioventricular (AV) conduction time is affected by the site of atrial pacing in anesthetized dogs. We paced the right atrium at a constant cycle length from the interatrial septum (IAS), superior coronary sinus (SCS), or inferior coronary sinus (ICS) regions, and we evaluated the time-dependent effects of vagal stimulation on AV conduction at each pacing site. When we stimulated the vagi at stimulus (St)-A phases greater than 136 +/- 40 ms and less than the phase that blocked AV conduction (182 +/- 70 ms), IAS pacing prolonged A-V intervals by 8.6 +/- 8.2 ms more than ICS pacing. A change in pacing site affected the A-V intervals by up to 30 ms when we stimulated the vagus at those times that caused the A-V intervals to prolong maximally. Furthermore, the effect of atrial pacing site on A-V intervals was modulated by AV nodal recovery times during the second or third cycles after the vagal stimulus.

Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions

1990 ◽  
Vol 258 (4) ◽  
pp. H1112-H1118 ◽  
Author(s):  
Y. Furukawa ◽  
D. W. Wallick ◽  
M. D. Carlson ◽  
P. J. Martin
Keyword(s):  
Nerve Fibers ◽  
Stimulation Frequency ◽  
Conduction Time ◽  
Heart Period ◽  
Activation Patterns ◽  
Parasympathetic Nerve ◽  
Chronotropic Response ◽  
Av Conduction ◽  
Sinus Cycle Length ◽  
Anesthetized Dogs

We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart.

Brief vagal bursts can induce Wenckebach arrhythmia

1989 ◽  
Vol 257 (3) ◽  
pp. H935-H941
Author(s):  
D. W. Wallick ◽  
P. J. Martin
Keyword(s):  
Feedback Control ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Feedback Control System ◽  
Pentobarbital Sodium ◽  
Control Loops ◽  
Av Conduction ◽  
Retrograde Conduction ◽  
Ventricular Depolarization ◽  
Wenckebach Arrhythmia

We hypothesized that a brief burst of vagal stimulation applied in each cardiac cycle could elicit an atrioventricular (AV) nodal Wenckebach arrhythmia. Twenty-six dogs were anesthetized with pentobarbital sodium (30 mg/kg iv) and were given propranolol (1 mg/kg iv). We varied the timing of a vagal stimulus burst in steps of 25-50 ms relative to the onset of atrial or ventricular depolarization. In four of nine experiments, a Wenckebach arrhythmia occurred despite changing the timing of stimuli. By prolonging the effects of vagal stimulation on AV conduction with physostigmine, the timing of the stimuli no longer influenced the severity of the arrhythmia. We did experiments to open one of the feedback control loops; these results indicated that this arrhythmia has elements of a positive feedback control system. We also studied the effects of vagal stimulation on the arrhythmia during retrograde conduction. We found that the timing of vagal stimulation was critical in eliciting the arrhythmia in only 4 of the 10 dogs.

Phasic effects of postganglionic vagal stimulation on atrioventricular nodal conduction

1986 ◽  
Vol 251 (3) ◽  
pp. H619-H630
Author(s):  
T. Mazgalev ◽  
L. S. Dreifus ◽  
E. L. Michelson ◽  
A. Pelleg ◽  
R. Price
Keyword(s):  
Cycle Length ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Conduction Time ◽  
Vagal Activity ◽  
Experimental Conditions ◽  
Sinus Cycle Length ◽  
Atrioventricular Nodal Conduction ◽  
Effective Phase ◽  
Vagal Influence

The effects of postganglionic vagal stimulation (PGVS) on atrioventricular nodal conduction were studied in 15 rabbit atrial-atrioventricular nodal preparations. PGVS was introduced, and sinus cycle length was scanned as independent bursts of subthreshold stimuli were produced in the sinus node and atrioventricular node (AVN). Changes in conduction of atrial impulses to the bundle of His were studied under the following experimental conditions: changes in sinus cycle length resulting from vagal influence on the sinus node, direct vagal stimulation exclusively to the AVN, and during both simultaneous or nonsimultaneous vagal stimulation to sinus node and AVN. The results of the present study showed that the direct effect of PGVS on AVN conduction time at a constant sinus cycle length is phase dependent with maximal prolongation achieved in the first or second beat after introduction of the burst. The interval between the onset of PGVS producing maximal prolongation of conduction time and the following atrial beat was designated the "optimal effective phase." It was shown that the optimal effective phase was a constant parameter for a given preparation and in the present experiments was 321 +/- 16 ms. However, when PGVS was introduced in combination to both nodes while scanning the cycle length, AVN conduction was variable, reflecting both the direct effects of PGVS on the AVN as well as the indirect effects resulting from changes in the sinus cycle length. Notably, it was found that simultaneous PGVS to both the sinus node and AVN usually diminished, whereas appropriate nonsimultaneous PGVS accentuated the typical phasic dependency of AVN conduction time. Additionally, vagally induced prolongation of the sinus cycle length was found to be accompanied by changes in the time of depolarization of the inputs to the AVN, thus influencing AVN conduction and facilitating reentry. These interactions between changes in the sinus cycle length and concomitant changes in the effectiveness of vagal influence on the AVN can be used to explain complexities of AVN conduction during increased vagal activity.

Secondary AV conduction responses during tonic vagal stimulation

1983 ◽  
Vol 245 (4) ◽  
pp. H584-H591 ◽  
Author(s):  
P. Martin
Keyword(s):  
Vagal Stimulation ◽  
Control Level ◽  
Negative Inotropic Effect ◽  
Initial Response ◽  
Secondary Response ◽  
Surrounding Tissue ◽  
Conduction Time ◽  
Initial Value ◽  
Cumulative Change ◽  
Av Conduction

We gave trains of supramaximal stimuli at frequencies of 2, 4, or 8 Hz to both vagi of anesthetized, open-chest dogs and studied the AV conduction and atrial contractility responses while the atria were paced at different frequencies. The vagal stimulation quickly induced a maximum negative inotropic effect on the atrium. This "initial" response was followed by a "secondary" fading back toward the control level. The negative dromotropic responses to vagal stimulation also rapidly reached an initial value. When this initial response was large, there was then a secondary, relatively rapid fading back toward control. However, when the initial dromotropic response was small, the secondary response instead consisted of a gradual increase in conduction time. At intermediate levels of the initial dromotropic response, there was no appreciable secondary change in AV response. We hypothesize that two opposing mechanisms account for the variable secondary changes in AV conduction time and that the stimulus intensity determines which mechanism will be prepotent. The mechanism responsible for the secondary decline appears to be related to that which causes the fade of the inotropic response; muscarinic receptor desensitization probably plays an important role. The secondary augmentation of the dromotropic response may be related either to a slow diffusion of acetylcholine from the surrounding tissue or to a slow cumulative change in AV nodal refractoriness.

Muscarinic autoreceptors do not modulate kinetics of acetylcholine release in hearts

1989 ◽  
Vol 256 (4) ◽  
pp. H1073-H1078
Author(s):  
F. Dexter ◽  
Y. Rudy ◽  
M. N. Levy
Keyword(s):  
Steady State ◽  
Time Delay ◽  
Time Course ◽  
Cardiac Cycle ◽  
Vagal Nerve ◽  
Interpulse Interval ◽  
Nerve Endings ◽  
Time Interval ◽  
Ach Release ◽  
Chronotropic Response

We determined the time course of the cellular mechanism that mediates the attenuation of the chronotropic response in anesthetized dogs to decreases in the time interval (interpulse interval) between pulses of vagal stimuli. We injected propranolol, cut the cervical vagi, and repetitively stimulated the cardiac segment of the right vagus nerve with one brief burst of electrical pulses during each cardiac cycle. We recorded the initial and steady-state changes in cardiac cycle length that were induced by the phasic vagal stimulation. The decrease in the interpulse interval decreased the initial and steady-state responses. The time delay between the release of acetylcholine (ACh) from the vagal nerve endings in the heart and inhibition of the release of additional ACh was less than 4 ms. Published delays between the time of ACh release and the time of the resulting change in membrane potential, in other biological systems, are 30-12,000 ms. We conclude that the time delay was too brief for muscarinic autoreceptors to have mediated the attenuation of ACh release from postganglionic vagal nerve endings in the heart in response to decreases in interpulse interval.

In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals

2001 ◽  
Vol 281 (1) ◽  
pp. H139-H145 ◽  
Author(s):  
Toru Kawada ◽  
Toji Yamazaki ◽  
Tsuyoshi Akiyama ◽  
Toshiaki Shishido ◽  
Masashi Inagaki ◽  
...  
Keyword(s):  
Heart Rate ◽  
Vagal Stimulation ◽  
Left Ventricular ◽  
Vagal Nerve ◽  
Local Administration ◽  
Nerve Terminals ◽  
Ach Release ◽  
Rate Dependent ◽  
Baroreceptor Reflexes

We examined whether the ACh concentration measured by cardiac microdialysis provided information on left ventricular ACh levels under a variety of vagal stimulatory and modulatory conditions in anesthetized cats. Local administration of KCl ( n = 5) and ouabain ( n = 7) significantly increased the ACh concentration in the dialysate to 4.3 ± 0.8 and 7.3 ± 1.3 nmol/l, respectively, from the baseline value of 0.6 ± 0.5 nmol/l. Intravenous administration of phenylbiguanide ( n = 5) and phenylephrine ( n = 6) significantly increased the ACh concentration to 5.4 ± 0.9 and 6.0 ± 1.5 nmol/l, respectively, suggesting that the Bezold-Jarisch and arterial baroreceptor reflexes affected myocardial ACh levels. Modulation of vagal nerve terminal function by local administration of tetrodotoxin ( n = 6), hemicholinium-3 ( n = 6), and vesamicol ( n = 5) significantly suppressed the electrical stimulation-induced ACh release from 20.4 ± 3.9 to 0.6 ± 0.1, 7.2 ± 1.9, and 2.7 ± 0.6 nmol/l, respectively. Increasing the heart rate from 120 to 200 beats/min significantly reduced the myocardial ACh levels during electrical vagal stimulation, suggesting a heart rate-dependent washout of ACh. We conclude that ACh concentration measured by cardiac microdialysis provides information regarding ACh release and disposition under a variety of pathophysiological conditions in vivo.

Supersensitivity to acetylcholine of canine sinus and AV nodes after parasympathetic denervation

1988 ◽  
Vol 255 (3) ◽  
pp. H534-H539 ◽  
Author(s):  
S. Kaseda ◽  
D. P. Zipes
Keyword(s):  
Dose Response ◽  
Cycle Length ◽  
Vagal Stimulation ◽  
Conduction Time ◽  
Av Block ◽  
Response Curves ◽  
Parasympathetic Ganglia ◽  
Sinus Cycle Length ◽  
Alpha Chloralose ◽  
Complete Av Block

Supersensitivity of the sinus (SAN) and atrioventricular (AVN) nodes to acetylcholine (ACh) after parasympathetic denervation has not been demonstrated conclusively. In this study, we denervated the SAN and AVN by surgically removing parasympathetic ganglia and painting the area with phenol. Sham dogs underwent thoracotomy without denervation. Four to 9 days later, vagal denervation was proved by supramaximal bilateral vagal stimulation, which prolonged the sinus cycle length (SCL) only 32 +/- 7% (mean +/- SE) and the AVN conduction time (AH interval) 15 +/- 7% in denervated dogs. We tested for supersensitivity by obtaining dose-response curves to ACh (1 ml, 10(-8.0) to 10(-4.0) M in 10(0.5) steps) infused over 15 s into the sinus nodal and posterior septal arteries in open chest-denervated (Den) dogs and in sham-operated (Sham) dogs that were anesthetized with alpha-chloralose. ACh concentration (Log[ACh], M) required to prolong SCL 50, 100, and 300% was -5.7 +/- 0.1, -5.6 +/- 0.1, and -5.4 +/- 0.1 in 10 Sham dogs vs. -6.4 +/- 0.1 (P less than 0.001), -6.3 +/- 0.1 (P less than 0.001) and -6.1 +/- 0.1 (P less than 0.001) in 11 Den dogs. ACh concentration necessary to produce second degree and complete AV block was -5.7 +/- 0.1 and -5.3 +/- 0.1 in 11 Sham dogs vs. -6.3 +/- 0.1 (P less than 0.001) and -5.8 +/- 0.1 (P less than 0.01) in 10 Den dogs. Because significantly lower doses of ACh prolonged SCL or produced AV block in Den compared with Sham dogs, we conclude that dogs with vagally denervated SAN and AVN develop a supersensitive response to ACh.

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