Effects of digoxin on the chronotropic responses to repetitive vagal stimules bursts in the dog

1984 ◽  
Vol 62 (11) ◽  
pp. 1411-1415 ◽  
Author(s):  
Daniel G. Pace ◽  
Yukitaka Masuda ◽  
Isaac Eisenstein ◽  
Matthew N. Levy
Keyword(s):  
Vagus Nerve ◽  
Cumulative Dose ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Cardiac Pacemaker ◽  
Pacemaker Cells ◽  
Chronotropic Response ◽  
Cycle Lengths ◽  
Anesthetized Dogs

We studied the effects of digoxin on the chronotropic responses of the heart to repetitive bursts of vagal stimulation in chloralose-anesthetized dogs. The frequency of the stimulus bursts was increased linearly with time. Over a certain range of frequencies, the cardiac pacemaker became synchronized with the vagal stimulation in a 1:1 ratio of heart beats to stimulus bursts. Digoxin increased the range of cardiac cycle lengths over which 1:1 synchronization occurred during repetitive vagal stimulation. This increment in the range of synchronization varied directly with the dose of digoxin. Before digoxin was given, the range of cardiac cycle lengths over which synchronization occurred when the vagus nerve was stimulated with 10 pulses per burst was 272 ± 50 (mean ± SE) ms. However, after a cumulative dose of 120 μg/kg−1 digoxin had been given, the range of 1:1 synchronization increased to 396 ± 32 ms. Digoxin did not appear to have a proportionately greater effect on those processes that take place in the phase of the cardiac cycle during which the pacemaker cells are maximally responsive than on those processes that occur in the phase of the cycle during which the pacemaker cells are minimally responsive. Therefore, we conclude that the augmented entrainment induced by digoxin is ascribable to its tendency to enhance the chronotropic response to vagal stimulation.

Changes in vagal phasic chronotropic responses with sympathetic stimulation in the dog

1981 ◽  
Vol 241 (6) ◽  
pp. H850-H856 ◽  
Author(s):  
S. L. Stuesse ◽  
D. W. Wallick ◽  
H. Zieske ◽  
M. N. Levy
Keyword(s):  
Cycle Length ◽  
Temporal Relationship ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Cardiac Response ◽  
Sympathetic Stimulation ◽  
Pacemaker Cells ◽  
Paradoxical Response ◽  
Chronotropic Response ◽  
Anesthetized Dogs

Sympathetic stimulation both shortens the cardiac cycle and potentiates the cardiac response to vagal stimulation. In the present study the effects of sympathetic stimulation on the chronotropic responses of the heart to brief bursts of vagal stimulation were determined in open-chest anesthetized dogs. The sinoatrial nodal pacemaker cells demonstrate a paradoxical response to repetitive bursts of vagal stimuli over a certain portion of the cardiac cycle. That is, the cardiac cycle length does not increase but actually decreases as the vagal stimulation frequency is raised. Background levels of sympathetic stimulation do not significantly alter the range over which this “paradoxical” response occurs. Sympathetic stimulation decreases the cardiac chronotropic response to short bursts of vagal stimuli regardless of the time in the cardiac cycle that the stimulus is given; however, it does not decrease the time from the minimum vagal chronotropic response to the subsequent atrial depolarization although the total cardiac cycle is shortened. Since sympathetic stimulation shifts the overall temporal relationship between vagal stimulation and pacemaker response, small changes in sympathetic tone may greatly alter the cardiac response to phasic vagal stimulation if the vagal stimulus is given at certain times in the cardiac cycle.

Effects of calcium channel antagonists on the vagally mediated cardiac chronotropic response in dogs

1990 ◽  
Vol 68 (10) ◽  
pp. 1363-1367 ◽  
Author(s):  
Don W. Wallick ◽  
Sherry L. Stuesse ◽  
Paul Martin
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Calcium Channel ◽  
Total Dose ◽  
Cycle Length ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Calcium Channel Antagonists ◽  
Chronotropic Response ◽  
Stimulation Of

A brief electrical stimulation of the vagus nerve may elicit a triphasic response comprising (i) an initial prolongation of the same or the next cardiac cycle, (ii) a return of the subsequent cardiac cycle to about the level prior to vagal stimulation, and (iii) a secondary prolongation of cardiac cycle length that lasts several beats. We compared the effects of two calcium channel antagonists, verapamil and nifedipine, on this triphasic response to vagal stimulation in chloralose-anesthetized, open-chest dogs. In the absence of vagal stimulation, nifedipine (doses of 10, 40, and 50 μg/kg for a total dose of 100 μg/kg, i.v.) and verapamil (two doses of 100 μg/kg each, i.v.) increased the cardiac cycle length (A–A interval) by 16% (429 ± 20 to 496 ± 21 ms) and 29% (470 ± 33 to 605 ± 54 ms), respectively. Nifedipine (100 μg/kg total) attenuated the initial vagally mediated prolongation of the A–A interval, from 474 ± 19 to 369 ± 42 ms above the basal A–A interval. Following the initial prolongation of the vagal effect, other A–A intervals were not affected. In contrast, verapamil potentiated the vagally mediated initial prolongation in cardiac cycle length at the first dose administered (100 μg/kg) from 492 ± 17 to 561 ± 14 ms, but other increases in dosages had no further effect. Thus these two calcium channel antagonists have different effects on the sinoatrial chronotropic responses caused by brief vagal stimulation.Key words: autonomic control, parasympathetic, heart, calcium.

Effects of catecholamines on cardiac chronotropic response to vagal stimulation in the dog

1983 ◽  
Vol 245 (5) ◽  
pp. H721-H724 ◽  
Author(s):  
C. Chassaing ◽  
P. Duchene-Marullaz ◽  
M. J. Veyrac
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Vagus Nerve ◽  
Neurotransmitter Release ◽  
Acetylcholine Release ◽  
Vagal Stimulation ◽  
Norepinephrine Release ◽  
Chronotropic Response ◽  
Anesthetized Dogs ◽  
Stimulation Of

The influence of isoproterenol, norepinephrine, and dopamine on the cardiomoderator effects of moderate vagal stimulation was studied in anesthetized dogs. The drugs were administered at increasing doses in successive perfusions. Stimulation of the vagus nerve, the parameters of which remained constant throughout each experiment, was performed immediately before each sequence of perfusion and after 10-min perfusion. Isoproterenol at 0.025, 0.05, 0.1, and 0.2 microgram X kg-1 X min-1 raised heart rate dose relatedly but did not alter heart rate under vagal stimulation. Thus the amplitude of vagal bradycardic effects increased dose relatedly. Norepinephrine at 0.125, 0.25, 0.5, and 1 microgram X kg-1 X min-1 lowered heart rate through reflex hypertension. Heart rate under vagal stimulation remained constant. Thus the effects of vagal stimulation decreased as dose increased, finally becoming null. Dopamine at 0.5, 1, 2.5, and 5 micrograms X kg-1 X min-1 did not significantly alter heart rate, but at 10 and 20 micrograms X kg-1 X min-1, like norepinephrine, it raised blood pressure, causing a reflex fall in heart rate. At all doses, heart rate under vagal stimulation remained stable. Consequently, at the highest doses, the net effects of vagal stimulation were slight. These results suggest the simultaneous involvement of sympathetic-parasympathetic interactions both post- and prejunctionally. In the latter case, different mechanisms of regulation of neurotransmitter release are involved during vagal stimulation according to the sympathomimetic used. With isoproterenol, norepinephrine release seems more particularly affected, whereas with norepinephrine and dopamine, acetylcholine release is apparently inhibited.

Effects of glucagon on cardiac chronotropic response to vagal stimulation in the dog

1982 ◽  
Vol 242 (1) ◽  
pp. H7-H12 ◽  
Author(s):  
S. L. Stuesse ◽  
M. N. Levy ◽  
H. Zieske
Keyword(s):  
Heart Rate ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Cardiac Response ◽  
Heart Period ◽  
Chronotropic Response ◽  
Postsynaptic Receptors ◽  
Vagolytic Effect ◽  
Cycle Lengths ◽  
Sympathetic Nervous

Glucagon accelerates the heart independent of sympathetic nervous system stimulation. The effect of glucagon on the chronotropic responses to repetitive bursts of vagal stimulation was determined in open-chest anesthesized dogs. When the cervical vagi were stimulated at constant frequencies, the change in heart rate was not affected by glucagon administration, i.e., no vagolytic effect caused by glucagon was apparent. Thus glucagon did not alter the reaction of acetylcholine with cardiac postsynaptic receptors. When the vagi were stimulated intermittently with one short burst of vagal stimuli delivered each cardiac cycle, the resultant heart period was dependent on the time of vagal stimulus delivery. Both maximum and minimum cardiac cycle lengths obtained during phasic vagal stimulation were decreased by glucagon. As it has been previously demonstrated that vagal impulses to the heart tend to be clustered during certain times of the cardiac cycle, by accelerating the heart glucagon may shift the cardiac response to vagal stimulation.

Verapamil potentiates vagally mediated sinoatrial chronotropic responses in dogs

1986 ◽  
Vol 64 (7) ◽  
pp. 954-957
Author(s):  
Don W. Wallick ◽  
Sherry L. Stuesse ◽  
Frank Valencic ◽  
Richard B. Fratianne
Keyword(s):  
Vagus Nerve ◽  
Cycle Length ◽  
Cardiac Cycle ◽  
Sinoatrial Node ◽  
Vagal Stimulation ◽  
Blocking Agent ◽  
Chronotropic Response ◽  
Channel Blocking ◽  
Initial Action ◽  
Electrical Stimuli

A brief burst of electrical stimuli delivered to the vagus nerve during the cardiac cycle elicits a triphasic cardiac chronotropic response. The cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. We studied the effects of a calcium channel blocking agent, verapamil, on these responses to vagal stimulation during sinoatrial nodal rhythm in anesthetized, open-chest dogs. Verapamil increased the basal cardiac cycle length only slightly; however, the primary cardioinhibition was accentuated approximately 40% (from 396 to 555 ms) by verapamil. Neither the acceleratory phase of this triphasic response nor the secondary cardioinhibition was significantly affected by verapamil. These results indicate that verapamil potentiates the initial action of acetylcholine at the sinoatrial node when the vagus is activated with brief stimuli.

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.

Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs

1979 ◽  
Vol 237 (3) ◽  
pp. H275-H281 ◽  
Author(s):  
D. W. Wallick ◽  
M. N. Levy ◽  
D. S. Felder ◽  
H. Zieske
Keyword(s):  
Cardiac Cycle ◽  
Sinus Node ◽  
Critical Time ◽  
Large Change ◽  
Vagal Activity ◽  
Vagus Nerves ◽  
Pacemaker Cells ◽  
Chronotropic Response ◽  
Sinus Node Artery ◽  
The Mean

A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.

Sustained increases in heart rate induced by timed repetition of vagal stimulation in dogs

1985 ◽  
Vol 249 (4) ◽  
pp. H703-H709
Author(s):  
T. Yang ◽  
M. D. Jacobstein ◽  
M. N. Levy
Keyword(s):  
Cycle Length ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Critical Time ◽  
Critical Value ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
The Right ◽  
Positive Chronotropic Effect

We determined the influence of the "free-running cycle length" (tau FR) on chronotropic responses to one burst of right vagal stimuli per cardiac cycle in anesthetized dogs (tau FR, cycle length that prevailed in absence of right vagal stimulation). We varied tau FR by the following methods: 1) tonic left vagal stimulation in pentobarbital-anesthetized animals; 2) tonic left vagal stimulation plus sinus node cooling in pentobarbital-anesthetized animals; and 3) anesthesia with fentanyl, droperidol, and pentobarbital. When tau FR was less than a critical value [1,019 +/- 60 (SE) ms], right vagal stimulus bursts always had the expected negative chronotropic effect. However, when the tau FR was increased beyond critical value, right vagal stimulus bursts delivered within a specific portion of cardiac cycle actually had a positive chronotropic effect; i.e., cycle lengths diminished to values below tau FR. As tau FR was progressively increased beyond critical value, positive chronotropic response became greater and could be evoked by stimulus bursts delivered within a greater fraction of cardiac cycle. The right vagal stimuli that elicited the maximum positive chronotropic effect were those that were given approximately 235 ms prior to beginning of next atrial depolarization. This critical time probably occurs near the end of the period of phase 4 depolarization of sinus node automatic cells.

Effects of ionic channel antagonists barium, cesium, and UL-FS-49 on vagal slowing of atrial rate in dogs

1997 ◽  
Vol 273 (5) ◽  
pp. H2155-H2160 ◽  
Author(s):  
Don W. Wallick ◽  
Akin Kuguoglu ◽  
Tianen Yang ◽  
Sherry L. Stuesse ◽  
Matthew N. Levy
Keyword(s):  
Potassium Current ◽  
Vagal Stimulation ◽  
Ionic Channels ◽  
Ionic Channel ◽  
Pacemaker Current ◽  
Atrial Rate ◽  
Cycle Lengths ◽  
Anesthetized Dogs

In response to a brief vagal stimulus, the atrial rate initially slows, then transiently accelerates, and slows a second time. We determined the effects of three antagonists to two ionic channels on this characteristic triphasic pacemaker response. Brief bursts of vagal stimulation were delivered to anesthetized dogs, and atrial cycle lengths were recorded. Either barium, cesium, or UL-FS-49 was administered. Barium, which primarily blocks the acetylcholine-sensitive potassium current ( I K,ACh), attenuated the initial vagally induced bradycardia by >50% without affecting the subsequent acceleration or the secondary slowing. Cesium and UL-FS-49 [both of which primarily block the pacemaker current ( I f)] did not affect the initial vagal slowing of atrial rate but abolished the acceleratory portion of the response. The secondary slowing was abolished by cesium but not by UL-FS-49. We conclude that the initial rapid atrial response to acetylcholine is mediated mainly by the I K,ACh, with little contribution from the I f. The subsequent acceleration is mediated by activation of the I f.

Effects of repetitive vagal stimulation on heart rate and on cardiac vasoactive intestinal polypeptide efflux

1995 ◽  
Vol 268 (5) ◽  
pp. H1939-H1946 ◽  
Author(s):  
M. R. Hill ◽  
D. W. Wallick ◽  
P. J. Martin ◽  
M. N. Levy
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Cardiac Pacemaker ◽  
Close Correlation ◽  
Right Atrial ◽  
Chronotropic Response ◽  
Sinus Node Artery ◽  
Stimulation Regimen ◽  
Intestinal Polypeptide

In dogs anesthetized with alpha-chloralose, we assessed the "vagally induced tachycardia" elicited by successive 2-min periods of intense vagal stimulation (0.5 ms, 10 mA, 20 Hz) after we had blocked the animals' muscarinic and beta-adrenergic receptors with atropine and propranolol, respectively. We found that the tachycardia produced by the successive vagal stimulations progressively decreased to < 20% of the initial tachycardia response within 84 min. We also observed that the chronotropic response to vasoactive intestinal polypeptide (VIP) injected into the sinus node artery after the vagal stimulation regimen did not differ significantly from the response to the same dose of VIP injected prior to vagal stimulation. This finding indicates that the postjunctional responsiveness of the cardiac pacemaker cells had not diminished over the course of the vagal stimulation regimen. In isolated, perfused right atrial preparations, we observed a close correlation between the efflux of VIP from the atrial tissues and the chronotropic responses to vagal stimulation. Our results support the hypotheses that 1) VIP is a mediator of vagally induced tachycardia, 2) the reduction in VIP efflux is associated with a diminished vagally induced tachycardia, and 3) the reduced efflux of VIP probably reflects a diminution in neuronal release, perhaps by depletion of this peptide from the vagus nerve endings consequent to the prolonged neural stimulation.

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