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.

Vagally induced hyperpolarization in atrioventricular node

1986 ◽  
Vol 251 (3) ◽  
pp. H631-H643 ◽  
Author(s):  
T. Mazgalev ◽  
L. S. Dreifus ◽  
E. L. Michelson ◽  
A. Pelleg
Keyword(s):  
Action Potentials ◽  
Cycle Length ◽  
Time Course ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Atrioventricular Node ◽  
Conduction Time ◽  
Sinus Cycle Length ◽  
Atrioventricular Nodal Conduction ◽  
The Moment

The effects of postganglionic vagal stimulation on atrioventricular nodal conduction were studied in 12 rabbit atrial-atrioventricular nodal preparations. Vagal stimulation was introduced in the sinus and atrioventricular nodes, separately or in combination, using single bursts of subthreshold stimuli. The sinus cycle length was scanned to identify the phasic effect of vagal stimulation. Action potentials from cells in the AN, N, and NH regions of the atrioventricular node were recorded by microelectrode techniques. Vagally induced hyperpolarization of cells in the atrioventricular node resulted in a phase-dependent prolongation of conduction time and reflected the level of residual hyperpolarization at the moment of arrival of the next atrial beat at the atrioventricular nodal input region. Vagally induced hyperpolarization was membrane potential dependent, although its overall time course was similar at different phases. Increased diastolic depolarization followed the maximal hyperpolarization. This "rebound" observed at certain phases was responsible for paradoxical shortening of the conduction time after vagal stimulation. The predominant effects of local vagal stimulation in the atrioventricular node were observed in cells in or near the N region. Slower rate of rise, shorter amplitude and duration, as well as step formations were among the changes in action potentials recorded from these cells. The effects of vagal stimulation were inhomogeneous between different regions of the atrioventricular node as well as within the N region, producing alternative pathways of conduction and the potential for reentry. The concomitant changes in sinus cycle length resulting from vagal stimulation in the sinus node region altered the phasic effects of vagal stimulation introduced in the atrioventricular node. This was related to a direct influence of the prolonged sinus cycle length on atrioventricular nodal refractoriness as well as an indirect effect on the degree of residual vagally induced hyperpolarization at the moment of arrival of the delayed atrial beat. These findings provide mechanistic explanations for the complex effects of vagal stimulation on atrioventricular nodal conduction.

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.

NO modulates autonomic effects on sinus discharge rate and AV nodal conduction in open-chest dogs

1997 ◽  
Vol 272 (1) ◽  
pp. H263-H271 ◽  
Author(s):  
A. Elvan ◽  
M. Rubart ◽  
D. P. Zipes
Keyword(s):  
Discharge Rate ◽  
Conduction Time ◽  
Minimum Concentration ◽  
Open Chest ◽  
Sympathetic Modulation ◽  
Sinus Cycle Length ◽  
Nos Inhibitor ◽  
Alpha Chloralose ◽  
Complete Av Block

The purpose of this study was to investigate the role of nitric oxide (NO) in mediating vagal and sympathetic modulation of spontaneous sinus cycle length (SCL) and atrioventricular (AV) nodal conduction time (A-H interval) in 62 open-chest mongrel dogs anesthetized with alpha-chloralose. Infusion of an NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 4 mg/ ml), into the sinus and AV nodal arteries attenuated significantly (P < 0.01) the negative chronotropic and dromotropic responses to vagal nerve stimulation (VS) and VS during ansae subclaviae stimulation (SS) or isoproterenol (Iso) infusion. Intravenous administration of L-arginine (100 mg/kg) reversed these responses toward control values, whereas D-arginine did not have a significant effect. L-NMMA significantly (P < 0.01) enhanced the effects of SS and Iso on SCL and A-H interval; L-arginine reversed these changes toward baseline. L-NMMA increased the minimum concentration of ACh needed to induce 50 or 100% prolongation of SCL or second-degree or complete AV block during concomitant Iso infusion. L-Arginine reversed these effects. NOS inhibition did not affect the direct cholinergic actions of ACh on SCL and A-H interval but enhanced adrenergic positive chronotropic and dromotropic effects. We conclude that NO plays a stimulatory role in mediating vagal neurotransmission and vagal modulation of sympathetic effects and an inhibitory role in mediating sympathetic neurotransmission.

Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition

1988 ◽  
Vol 65 (5) ◽  
pp. 1944-1949 ◽  
Author(s):  
P. J. Antol ◽  
S. J. Gunst ◽  
R. E. Hyatt
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Prostaglandin Synthesis ◽  
Response Curves ◽  
Synthesis Inhibition ◽  
High Concentrations ◽  
Alpha Chloralose ◽  
Prostaglandin Synthesis Inhibitors

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.

Direct and reflex bronchoconstriction induced by histamine aerosol inhalation in dogs

1981 ◽  
Vol 50 (4) ◽  
pp. 869-873 ◽  
Author(s):  
M. A. Yanta ◽  
S. H. Loring ◽  
R. H. Ingram ◽  
J. M. Drazen
Keyword(s):  
Dose Response ◽  
Vagal Stimulation ◽  
Direct Effects ◽  
Pulmonary Resistance ◽  
Response Curves ◽  
Mechanically Ventilated ◽  
Efferent Activity ◽  
Aerosol Inhalation ◽  
Dose Response Curves

Histamine aerosols were administered to nine anesthetized, paralyzed, mechanically ventilated mongrel dogs with the cervical vagi first intact, then sectioned, and then peripherally stimulated at two intensities. Pulmonary resistance (RL) was measured, and dose-response curves were constructed in the four conditions. All dogs had dose-related increases in RL with increasing histamine aerosol concentrations. After the vagi were cut, the degree to which constant levels of vagal stimulation altered the dose-response relationships was assessed by examining the slopes and positions of the RL vs. histamine curves. Four of the nine animals studied showed evidence of increasing vagal efferent activity as the concentration of histamine in the aerosol increased, but three did not. Two of the dogs had equivocal responses in that increasing activity was suggested but not clearly demonstrated. These results indicate that, in addition to direct effects of histamine, the extent of and basis for vagal interaction with this stimulus varies among dogs. The results suggest that the basis of vagal interaction is related to either constant efferent activity (tone) or increasing efferent activity (reflexes).

Characterization of responses of neonatal sinus and AV nodes to critically timed, brief vagal stimuli

1991 ◽  
Vol 260 (2) ◽  
pp. H459-H464 ◽  
Author(s):  
S. Yamasaki ◽  
A. Stolfi ◽  
A. S. Pickoff
Keyword(s):  
Cycle Length ◽  
Cardiac Cycle ◽  
Gradual Increase ◽  
Latency Period ◽  
Atrial Pacing ◽  
Response Curves ◽  
Stimulus Train ◽  
Sinus Cycle Length ◽  
The Right

We studied the responses of sinus cycle length and atrioventricular (AV) nodal conduction to brief, critically timed vagal stimuli in 25 neonatal (9.6 +/- 3.1 days) canines. Vagal stimuli were delivered to the right or left decentralized cervical vagosympathetic trunk as either a single, brief stimulus train or a repetitive, phase-coupled train with both stimulation paradigms programmed to scan the entire cardiac cycle. The effects of brief vagal stimuli on cardiac cycle length were measured while the heart was beating spontaneously, and the vagal effects on AV nodal conduction were measured while the cycle length was held constant by atrial pacing at 300 ms. Neither changes in sinus cycle length nor AV nodal conduction demonstrated classical phase dependency, i.e., a gradual increase in the magnitude of the vagal response as stimuli are delivered progressively later in the cardiac cycle until the latency period (that point in the cardiac cycle at which vagal stimulation no longer affects the next cardiac cycle) is reached. Phase-response curves (PRCs) to single and repetitive stimuli typically exhibited either a flat response or a small decrease in magnitude as the latency period of the PRC was approached. Thus the neonatal sinus and AV node PRCs exhibit a different configuration than that reported in the adult.

Modulation of electrophysiological properties of neonatal canine heart by tonic parasympathetic stimulation

1990 ◽  
Vol 258 (1) ◽  
pp. H38-H44 ◽  
Author(s):  
A. S. Pickoff ◽  
A. Stolfi
Keyword(s):  
Cycle Length ◽  
Parasympathetic Nervous System ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Right Atrial ◽  
Conduction Time ◽  
Canine Heart ◽  
Electrophysiological Properties ◽  
Refractory Periods ◽  
The Right

The effects of tonic right and left vagal stimulation (RVS and LVS) on electrophysiological properties of the immature myocardium and specialized conduction system were evaluated in 11 neonatal canines pretreated with propranolol (1 mg/kg iv). Electrophysiological studies were performed by recording intracardiac electrograms from multiple endocardial catheters during programmed electrical stimulation. Assessments were made of sinus node function, intra-atrial, atrioventricular (AV) nodal and His-Purkinje conduction, and atrial and ventricular refractoriness in the control state and during RVS and LVS at 4–12 Hz. Vagal stimulation prolonged the sinus cycle length; RVS produced a 38% increase and LVS a 25% increase at 8 Hz (P less than 0.01). There were no changes in the intra-atrial or His-Purkinje conduction times. Comparable increases occurred during RVS and LVS in the paced cycle length resulting in AV nodal Wenckebach, the AV nodal conduction time at a paced cycle length of 340 ms, and the effective and functional refractory periods of the AV node, suggesting symmetrical influences of the right and left vagus on neonatal AV nodal function. Right atrial effective and functional refractory periods shortened significantly during vagal stimulation (ERP, 36% RVS and 23% LVS; FRP, 27% RVS and 15% LVS), and in 5 of 11 neonates, a sustained regular atrial tachyarrhythmia was induced during atrial extra-stimulation. Small yet significant increases were observed in the right ventricular ERP and FRP during vagal stimulation. This study provides information regarding the functional integrity of the parasympathetic nervous system and its potential role as a modulator of the electrophysiological properties of the newborn heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of propafenone on sinus node function in the rabbit heart

1990 ◽  
Vol 68 (7) ◽  
pp. 851-855 ◽  
Author(s):  
Charles R. Kerr
Keyword(s):  
Cycle Length ◽  
Sinus Node ◽  
Rabbit Heart ◽  
Conduction Time ◽  
Supraventricular Arrhythmias ◽  
Sinus Cycle Length ◽  
Cycle Lengths ◽  
Dose Dependent ◽  
Control State

Propafenone is a type 1C antiarrhythmic drug with efficacy for both ventricular and supraventricular arrhythmias. We investigated the effects of propafenone on properties of sinus node function in an in vitro preparation of rabbit sinus node and surrounding atrium. Spontaneous sinus cycle length (SCL), atriosinus conduction time (ASCT), and sinus node effective refractory period (SNERP) at multiple pacing cycle lengths were measured in the control state and during superfusion with propafenone (2.3 μM). SNERP prolonged from 175 ± 25 ms in the control state to 220 ± 45 ms (p < 0.001) with propafenone. ASCT also prolonged significantly (p < 0.01) from 50 ± 20 to 65 ± 20 ms whereas SCL did not change. In four experiments, multiple concentrations of propafenone were utilized and there appeared to be a dose-dependent prolongation of SNERP. Thus, propafenone has a significant effect on SNERP and ASCT in an isolated rabbit sinus node preparation.Key words: propafenone, sinus node, atrium.

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.

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