Effect of vasoactive intestinal peptide on pacemaker location and heart rate in the dog atrium

1998 ◽  
Vol 76 (4) ◽  
pp. 457-462 ◽  
Author(s):  
Arnold Pintér ◽  
Réginald Nadeau ◽  
Nazih Dandan ◽  
Pierre L Pagé
Keyword(s):  
Heart Rate ◽  
Vasoactive Intestinal Peptide ◽  
Sinus Node ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Similar Decrease ◽  
Intravenous Sodium ◽  
Unipolar Electrograms ◽  
Positive Chronotropic Effect ◽  
Atrial Mapping

Vasoactive intestinal polypeptide (VIP) was either injectedintravenously (300 pmol·kg–1) or perfused (1 nmol in 1 min) into the sinusnode artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers.Isochronal maps were obtained from 128 unipolar electrograms recorded on the epicardialsurface of both atria in nine animals. When VIP was perfused into the SNA or injectedintravenously, heart rate increased by 29 ± 16% and 12 ± 12%, and blood pressure decreased by16 ± 15 mmHg (1 mmHg = 133.3 Pa) and 24 ± 18 mmHg, respectively. Nosignificant change in heart rate (3 ± 6% decrease) accompanied a similar decrease in bloodpressure after an intravenous sodium nitroprusside perfusion. The perfusion of VIP into the SNAas well as the intravenous injection of VIP induced a shift of the pacemaker site to the region ofBachmann’s bundle in a third of the preparations, while the pacemaker remained in the sinusnode area in two thirds. A perfusion of isoproterenol into the SNA produced a similar heart rateincrease (32 ± 14%, NS vs. VIP), and shifted the pacemaker site rostrally within the sinus node inthree of five preparations, or to the region of Bachmann’s bundle in two of five preparations.The response to VIP in the location of the pacemaker was significantly different from theresponse to isoproterenol. Repeated perfusions of VIP into the SNA after 10-, 25-, 40-, and60-min intervals produced 2 ± 13% (p < 0.005 vs. the effect of first VIP administration),14 ± 12% (p < 0.05), 10 ± 12% (p < 0.05) and 30 ± 13% (NS) heart rateincreases, respectively, thereby demonstrating a tachyphylactic effect. In conclusion, VIP seemsto exert its positive chronotropic effect directly (probably via specific VIP receptors), althoughthe phenomenon of tachyphylaxis may suggest an indirect sympathomimetic mechanism.Key words: vasoactive intestinal peptide,subsidiary atrial pacemakers, sinus node artery, atrial mapping.

Evaluation of β-Adrenerglc Blocking Agents in Presence of Adrenergic Tone

1972 ◽  
Vol 50 (5) ◽  
pp. 381-388
Author(s):  
Victor Elharrar ◽  
Reginald A. Nadeau
Keyword(s):  
Dose Response ◽  
Sinus Node ◽  
Stellate Ganglion ◽  
Sodium Pentobarbital ◽  
Response Curves ◽  
Chronotropic Response ◽  
Blocking Agents ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
The Right

The importance of the level of adrenergic tone in the determination of the dose–response curve to noradrenaline (NA) and in the evaluation of β-adrenergic blocking agents was studied in open-chest sodium pentobarbital anesthetized dogs by injecting drugs directly into the sinus node artery. Changes in the level of adrenergic tone by stimulating the right stellate ganglion resulted in variation of the observed chronotropic response to NA and of its ED50. The chronotropic responses were corrected by taking into account the underlying adrenergic tone. The negative chronotropic effect of dl-propranolol (1 and 10 μg) appeared to be related to its β-blocking properties and not to its quinidine-like effects as shown by the lack of effect of d-propranolol injected at the same doses. The magnitude of the negative chronotropic effects of 10 μg of propranolol and 100 μg of practolol, oxprenolol, and sotalol was shown to be related to the initial heart rate and consequently to the level of adrenergic tone. The comparison of these four β-blocking agents was carried out on corrected dose-response curves to NA. Their relative potencies were found to be: propranolol > oxprenolol > practolol > sotalol, corresponding to ratios of 1, [Formula: see text], [Formula: see text], and [Formula: see text]

Sinus bradycardia during injections directly into the sinus node artery

1963 ◽  
Vol 204 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Thomas N. James ◽  
Reginald A. Nadeau
Keyword(s):  
Heart Rate ◽  
Sinus Bradycardia ◽  
Sinus Node ◽  
Normal Heart ◽  
Anatomic Structure ◽  
Ionic Content ◽  
Sinus Node Artery ◽  
Nutrient Artery ◽  
Normal Heart Rate ◽  
Cervical Vagotomy

In over 90% of 800 experiments in 75 dogs injection directly into the sinus node artery produced sinus bradycardia. Studies to explain this phenomenon included control of temperature, pH, osmolarity, oxygen, and ionic content of injecting solutions. Although unphysiologic variations of any of these are known to produce marked alterations in the sinus mechanism, sinus bradycardia from injection still occurred when they were controlled. Neurogenic mechanisms were excluded by bilateral cervical vagotomy, and by direct perfusion of the sinus node with atropine, hexamethonium, and trimethaphan. Because of the unique anatomic structure of the sinus node, which completely surrounds its nutrient artery, it is suggested that the sinus bradycardia may simply be the consequence of distending the sinus node artery. Implications concerning autoregulation of the normal heart rate are discussed.

Direct effects in vivo of angiotensins I and II on the canine sinus node

1991 ◽  
Vol 69 (3) ◽  
pp. 389-392 ◽  
Author(s):  
C. Lambert ◽  
D. Godin ◽  
P. Fortier ◽  
R. Nadeau
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Sinus Node ◽  
Converting Enzyme ◽  
Chronotropic Effect ◽  
Angiotensin I ◽  
Sinus Node Artery ◽  
Blood Pressures

The chronotropic responses to angiotensins I and II (5 μg in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 μg/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 ± 6 vs. 133 ± 6 beats/min) and in systemic systolic (134 ± 13 vs. 157 ± 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 ± 10 vs. 126 ± 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 ± 8 vs. 180 ± 25 mmHg) and diastolic (103 ± 8 vs. 145 ± 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 ± 11 vs. 88 ± 12 mmHg) and diastolic (84 ± 9 vs. 59 ± 9 mmHg) blood pressures without affecting the heart rate (109 ± 6 vs. 106 ± 6 beats/min). Saralasin produced a significant increase in systolic (109 ± 7 vs. 126 ± 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin. The antagonism by captopril of the response to angiotensin I suggests the presence of local tissue converting enzyme activity in the region of the sinus node.Key words: angiotensin, chronotropic effect, tissue converting enzyme.

Effects of neuropeptides on heart rate in dogs: comparison of VIP, PHI, NPY, CGRP, and NT

1988 ◽  
Vol 255 (2) ◽  
pp. H311-H317 ◽  
Author(s):  
D. F. Rigel
Keyword(s):  
Heart Rate ◽  
Neuropeptide Y ◽  
Vasoactive Intestinal Polypeptide ◽  
Sinus Node ◽  
Calcitonin Gene Related Peptide ◽  
Adrenergic Blockade ◽  
Related Peptide ◽  
Sinus Node Artery ◽  
Calcitonin Gene ◽  
Intestinal Polypeptide

This study was designed to evaluate the potential chronotropic actions of several cardiac neuropeptides in pentobarbital-anesthetized dogs. After bilateral vagotomy and stellectomy and muscarinic receptor blockade, I injected vasoactive intestinal polypeptide, peptide histidine isoleucine, neuropeptide Y, neurotensin, and calcitonin gene-related peptide into the intact sinus node artery. Neurotensin, calcitonin gene-related peptide, and neuropeptide Y exhibited no physiologically significant changes in heart rate. However, the structural homologues vasoactive intestinal polypeptide and peptide histidine isoleucine each augmented heart rate with maximal increases (approximately 120 beats/min) similar to those of norepinephrine. Vasoactive intestinal polypeptide and peptide histidine isoleucine were twice and 1/18, respectively, as potent as norepinephrine. The cardioacceleratory responses to vasoactive intestinal polypeptide and peptide histidine isoleucine were more slowly developing and longer lasting than those of norepinephrine. The responses to these two peptides were unchanged after beta-adrenergic blockade with propranolol in a dose sufficient to eliminate or greatly attenuate the norepinephrine tachycardia. These results indicate a potential role of endogenous vasoactive intestinal polypeptide and peptide histidine isoleucine in nonadrenergic, noncholinergic heart rate control in the dog.

Vasoactive intestinal polypeptide antagonists attenuate vagally induced tachycardia in the anesthetized dog

1995 ◽  
Vol 269 (4) ◽  
pp. H1467-H1472 ◽  
Author(s):  
M. R. Hill ◽  
D. W. Wallick ◽  
L. R. Mongeon ◽  
P. J. Martin ◽  
M. N. Levy
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Adrenergic Receptor ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
The Other ◽  
Vagus Nerves ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Intestinal Polypeptide

We used three vasoactive intestinal polypeptide (VIP) antagonists, VIP-(10-28), [p-Cl-D-Phe6,Leu17]VIP, and NT-VIP, to evaluate the role of VIP as a mediator of vagally induced tachycardia in chloralose-anesthetized dogs. After we administered muscarinic and beta-adrenergic receptor antagonists, we evoked vagally induced tachycardia either directly, by stimulating the vagus nerves for 2 min, or reflexly, by injecting phenylephrine to increase blood pressure. Furthermore, each of the antagonists attenuated the tachycardias induced by vagal stimulation by approximately 50% and the reflexly induced tachycardias by approximately 70%. Each VIP antagonist attenuated the chronotropic responses that we evoked by injecting VIP (5.2 ng/kg) into the sinus node artery. We tested the specificity of these VIP antagonists by determining whether they attenuated the increases in heart rate evoked by two other neuropeptides [peptide histidine isoleucine (PHI) and glucagon]. VIP-(10-28) attenuated the response to PHI, but not to glucagon. The other two VIP antagonists did not alter the chronotropic responses to PHI or glucagon. Our results support the hypothesis that neurally released VIP is the principal mediator of vagally induced tachycardia in the dog.

Vasoactive intestinal polypeptide enhances automaticity of supraventricular pacemakers in anesthetized dogs

1991 ◽  
Vol 261 (2) ◽  
pp. H463-H468 ◽  
Author(s):  
D. F. Rigel ◽  
D. A. Lathrop
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Sinus Node ◽  
Cardiac Pacemaker ◽  
Autonomic Nerve ◽  
Beta Adrenergic ◽  
Pentobarbital Sodium ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Muscarinic Cholinergic ◽  
Intestinal Polypeptide

Effects of the cardiac neuropeptide vasoactive intestinal polypeptide (VIP) and isoproterenol (ISO) were compared on sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker automaticity in pentobarbital sodium-anesthetized dogs (n = 14). Autonomic cardiac nerves were decentralized by bilateral vagotomy and stellectomy. VIP and ISO (30, 100, and 300 pmol/kg iv) were administered during sinus rhythm and either after crushing the sinus node to unmask a latent subsidiary atrial pacemaker (n = 7 dogs) or after injecting pentobarbital sodium into the sinus node artery to elicit an atrioventricular junctional pacemaker (n = 7). Spontaneous sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker rates (after autonomic nerve decentralization) were 142 +/- 4, 114 +/- 3, and 79 +/- 4 beats/min (means +/- SE), respectively. Both VIP and ISO dose dependently increased the rates of all three pacemaker sites. Combined muscarinic-cholinergic (atropine; 0.11 mg/kg iv) and beta-adrenergic receptor blockade (nadolol; 0.5 mg/kg iv) abolished the stimulatory effects of ISO on subsidiary atrial and atrioventricular junctional pacemakers but did not affect the responses to VIP. We conclude that exogenous VIP enhances the automaticity of sinus nodal, subsidiary atrial, and atrioventricular junctional pacemakers independently of muscarinic-cholinergic and beta-adrenergic receptors. Based on the previous demonstration of VIP-immunoreactive nerves throughout the heart, our findings also suggest that endogenous VIP may be involved in cardiac pacemaker regulation.

Postpacing tachycardia: autonomic involvement

1987 ◽  
Vol 253 (2) ◽  
pp. H333-H340
Author(s):  
J. M. Loeb ◽  
J. M. deTarnowsky ◽  
M. R. Warner ◽  
C. C. Whitson
Keyword(s):  
Heart Rate ◽  
Sinus Node ◽  
Atrial Pacing ◽  
Absolute Level ◽  
Time To Peak ◽  
Stellate Ganglia ◽  
Atrial Capture ◽  
Anesthetized Dogs ◽  
Alpha Chloralose ◽  
Control State

The cessation of pacing from the sinus node region is followed by a transient sinus tachycardia or postpacing tachycardia (PPT). We sought to characterize autonomic involvement in PPT. We used alpha-chloralose-anesthetized dogs and recorded electrocardiograms, blood pressure, and electrograms from the sinus node, right atrium, right ventricle, and His bundle. Both vagi and both stellate ganglia were transected. PPT developed immediately after either linear or stepped heart rate changes. PPT followed pacing from the rostral but not the caudal region of the sulcus terminalis. Independent manipulation of absolute level of heart rate (+33, +66, and +100 beats/min above control) and duration of atrial pacing (10, 20, and 30 s) revealed that PPT is dependent predominantly on the duration of pacing and less on level of heart rate. During pacing in the control state, a 1:1 atrial capture was maintained. After atropine administration (0.2 mg/kg iv), PPT increased significantly in magnitude, time to peak PPT was shortened significantly, and loss of 1:1 atrial capture during pacing was evident at pacing rates of from 10 to 60 beats above control. In contrast, propranolol significantly attenuated PPT. We conclude that acetylcholine, released during pacing from the sinus node region, suppresses inherent sinus node acceleration induced by the concurrent release of intramural catecholamines. During pacing, acetylcholine release is essential for the maintenance of 1:1 atrial capture and significantly modulates both the latency and magnitude of PPT.

Vagal-induced tachycardia: release of vasoactive intestinal peptide and peptide HI

1994 ◽  
Vol 267 (5) ◽  
pp. H2019-H2024
Author(s):  
F. L. Anderson ◽  
A. C. Kralios ◽  
N. Cluff ◽  
G. R. Hanson
Keyword(s):  
Heart Rate ◽  
Vasoactive Intestinal Peptide ◽  
Coronary Sinus ◽  
Nicotinic Receptors ◽  
Vagal Stimulation ◽  
Concentration Difference ◽  
Anesthetized Dogs ◽  
Alpha Chloralose ◽  
The Relationship ◽  
Coronary Sinus Blood

The relationship between vagal-induced tachycardia (VT) and release of vasoactive intestinal peptide (VIP) and peptide HI (PHI) into cardiac lymph and coronary sinus blood was studied in 23 alpha-chloralose-anesthetized open-chest dogs that were autonomically decentralized and pretreated with atropine and propranolol. After simultaneous right and left cervical vagal stimulation at 5 V, 20 Hz for 3 min mean +/- SE, increase in heart rate was 38 +/- 6 beats/min, and increase in lymph VIP output from control was 0.308 +/- 0.093 pg/min (P = 0.004). The decrease in VIP arterial minus coronary sinus concentration was not significant. The increase in heart rate did not significantly correlate with increase in lymph VIP output (R2 = 0.141) or decrease in VIP arterial minus coronary sinus concentration (R2 = 0.059). The increases in heart rate and lymph VIP output were blocked by hexamethonium. Increase in lymph PHI output from control during VT (5 dogs) was 0.797 +/- 0.658 pg/min. Arterial-coronary sinus PHI concentration difference did not change in these dogs. These data indicate that VT is associated but not significantly correlated with VIP and PHI release into cardiac lymph. Cholinoceptive nicotinic receptors may mediate VIP release and VT in anesthetized dogs.

Sign in / Sign up

Export Citation Format

Share Document