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Biomedical subjects

A Pelleg

Publications and source records attributed to A Pelleg.

At least 55 records · Page 3Linked to original sources
PubMed1988

Interacting negative chronotropic effects of adenosine and the vagus nerve on the canine sinus node.

The vagus nerve and adenosine exert a negative chronotropic effect on the mammalian sinus node. In addition, adenosine is released from myocardial cells under both physiological and pathophysiological conditions, which are characterised by variable vagal tone. To determine the interaction between adenosine and the vagus nerve, 21 barbiturate anaesthetised mongrel dogs with bilateral cervical vagotomy and stellectomy were studied. In group 1 (n = 16) adenosine (3 mumol.kg-1) was rapidly (less than or equal to 1 s) administered before (control) and during 60 s of repetitive vagal stimulation. Each stimulus (consisting of a burst of 5 square wave pulses, 0.3 mA in amplitude and 1 ms in duration at 0.1 kHz) was given at a fixed point in time in each sinus cycle (that is, one burst per cycle). This protocol was repeated after a 50 ms incremental change in the phase at which vagal stimulation was given until the entire cycle length was scanned. Recovery time of at least 2 min separated any two consecutive adenosine administrations. In four animals the above protocol was performed twice using vagal stimulation amplitude of 0.3 mA and 0.6 mA in the first and second runs respectively. In this group (group 1), the effect of adenosine was altered by the vagus in a phase dependent manner. In each animal, however, there was at least one phase of the sinus cycle during which vagal stimulation significantly enhanced the effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

On the mechanisms of cardiac electrophysiologic actions of adenosine and adenosine 5'-triphosphate.

Adenosine and ATP exert pronounced electrophysiologic actions on the mammalian heart including a negative chronotropic action on cardiac pacemakers and a negative dromotropic action on atrioventricular conduction. These actions are modulated by complex interactions of the two compounds with the autonomic nervous system. Since both adenosine and ATP are released from myocardial cells under physiologic and pathophysiologic conditions, they could play an important modulating role in cardiac electrophysiology. Indeed, studies during the last decade have yielded strong evidence for the role of adenosine in the genesis of specific arrhythmias associated with myocardial ischemia. Further studies are required to fully elucidate the mechanisms of actions of adenosine and ATP in vivo. These will undoubtedly enhance the understanding of the potential arrhythmogenic, as well as the antiarrhythmic actions of endogenous and exogenous adenosine and ATP.

Adenosine↗
PubMed1987

Role of the vagus in modulation by Ca2+ of the depressant action of adenosine and adenosine 5'-triphosphate on the canine sinus node in vivo.

1 The effect of elevated plasma Ca2+ level on the depressant action of adenosine and adenosine 5'-triphosphate (ATP) on the sinus node was studied in a canine model in vivo. 2 Under baseline conditions, both adenosine and ATP (3 mumol/kg) administered as a rapid bolus injection into the right atrium, caused a transient (less than 120 s) prolongation of sinus cycle length (SCL) of 128 +/- 25 ms and 439 +/- 31 ms respectively (P less than 0.02). 3 Infusion of CaCl2 (0.025 mmol/kg/min for 40 min) prolonged SCL from 257 +/- 17 ms to 418 +/- 17 ms (at t = 40 min; P less than 0.05), but did not significantly change arterial blood pressure. 4 Ca2+ infusion had no significant effect on SCL prolongation caused by adenosine (128 +/- 25 ms vs 151 +/- 31 ms; before and at t = 40 min respectively), but caused pronounced enhancement of SCL prolongation caused by ATP (439 +/- 31 ms vs 1215 +/- 401 ms; before and at t = 40, respectively, P less than 0.02). 5 Atropine (0.2 mg/kg, i.v.) did not affect the action of adenosine before or during Ca2+ infusion. In contrast, atropine abolished SCL prolongation by Ca2+ and abolished Ca2+ enhancement of the action of ATP. 6 The present data give further support to the hypotheses that (a) calcium potentiates vagally mediated actions and (b) the vagus is involved in the differential electrophysiological actions of adenosine and ATP in the canine heart in vivo.

Adenosine↗
PubMed1987

Canine AV nodal artery: anatomical variations and a detailed description of cannulation technique.

Cannulation of the atrioventricular (AV) nodal artery for selective perfusion of the AV node is a useful physiological method for evaluating the direct effects of pharmacological agents on the AV node. However, previous reports have not included a detailed description of the technique for AV nodal artery cannulation. Furthermore, successful cannulation is dependent on familiarity with the anatomical variations of the AV nodal artery [i.e., the most superior posterior septal artery (PSA)], which supplies blood to the AV nodal region and the posterior descending artery (PDA). The purpose of this report is to describe in detail the technique for cannulation of the AV nodal artery as well as the common anatomical variations of this artery. The anatomy of the PDA and PSA was studied at postmortem examination with ink injection in 30 dogs. Verification of the anatomical location of the AV nodal artery was aided by the induction of transient AV nodal conduction block following intracoronary administration of acetylcholine in the beating heart, as was done in previous studies. Two main variations and two subtypes of PDA anatomy and three main variations of AV nodal artery were found. Based on the present findings, an improved technique for cannulation of the AV nodal artery was established. Using this technique, we achieved a high rate of successful cannulation.

Animals↗
PubMed1987

Interactive negative chronotropic actions of adenosine and verapamil on the canine sinus node in vivo.

To study the interaction between adenosine and verapamil, adenosine (3 mumol/kg) was administered rapidly into the right atrium before and following verapamil (0.2 mg/kg, i.v.) in 25 pentobarbital anesthetized dogs divided into 4 groups: I (n = 7) - intact dogs; II (n = 6) - dogs pretreated with atropine (0.2 mg/kg, i.v.); III (n = 6) - dogs pretreated with propranolol (1 mg/kg, i.v.) and IV (n = 6) - bilateral stellectomized and cervical vagotomized dogs. Arterial blood pressure, standard lead II ECG, as well as right atrial, right ventricular and His bundle electrograms were continuously monitored and recorded. The negative chronotropic effect of adenosine was determined as the maximal prolongation in sinus cycle length (SCL). Verapamil maximally prolonged SCL by 70 +/- 14 msec (p less than 0.005) in Group I, 39 +/- 15 msec (0.1 greater than p greater than 0.005) in Group II, 86 +/- 18 msec (p less than 0.01) in Group III and by 100 +/- 12 msec (p less than 0.001) in Group IV. In Group I, control dogs, adenosine increased SCL by 82 +/- 21 msec before vs. 185 +/- 35 msec 15 minutes after verapamil, respectively (p less than 0.05). This potentiating effect of verapamil was completely abolished by atropine and markedly attenuated by propranolol. In stellectomized + vagotomized dogs, adenosine-verapamil interaction was more complex. In this group adenosine prolonged sinus cycle length maximally by 270 +/- 41 msec before verapamil, but following verapamil this effect of adenosine was transiently attenuated with a maximal sinus cycle length prolongation of only 165 +/- 24 msec (10 minutes following verapamil) (p less than 0.05, vs. before verapamil). These data indicate that the autonomic nervous system modulate the interactive negative chronotropic effects of adenosine and verapamil in the canine sinus node. Hence, the adenosine-verapamil interaction has clinical implications for conditions in which release of adenosine is increased (e.g. myocardial ischemia) or adenosine is administered in the presence of verapamil.

Adenosine↗
PubMed1987

Vagal component in the chronotropic and dromotropic actions of adenosine and ATP.

Several studies indicate that the vagus plays an important modulating role in the electrophysiologic actions of exogenous adenosine and ATP in the heart of certain mammalian species. In addition, extracellular adenosine can enhance the depressant effects of the vagus on the heart. These findings have immediate clinical implication with regard to the use of adenosine and ATP as antiarrhythmic agents as well as the mechanism of cardiac arrhythmias associated with high vagal tone and/or elevate extracellular adenosine levels.

Adenosine↗
PubMed1987

Adenosine mediates the negative chronotropic action of adenosine 5'-triphosphate in the canine sinus node.

ATP exerts pronounced electrophysiologic effects in the mammalian heart. The present study tested the hypothesis that the negative chronotropic action of ATP in the canine sinus node is dependent on its degradation to adenosine. Increasing doses of the following compounds were administered in the sinus nodal artery of 12 open chest dogs (either sex, 30-35 kg) anesthetized with pentobarbital (30 mg/kg i.v.): adenosine, ATP, alpha,beta methylene-ATP (AMPCPP) and beta,gamma methylene-ATP (AMPPCP). Right atrial, His bundle and right ventricular electrograms as well as Lead II ECG and systemic arterial blood pressure were monitored continuously and recorded. The depressant effects of test compounds on the sinus node were assessed from the prolongation of sinus cycle length and the duration of junctional escape rhythm which they induced. Data were used to plot dose-response curves for the four test compounds. The order of potency was adenosine greater than or equal to ATP greater than or equal to AMPPCP much greater than AMPCPP = 0. In 3 of 12 dogs the emergence of junctional escape rhythm was observed after the highest dose of either adenosine, ATP or AMPPCP. In addition, aminophylline, a selective competitive inhibitor of adenosine at P1-purinoceptor site, reduced the effects of maximal doses of adenosine, ATP and AMPPCP by 52 +/- 7, 67 +/- 8 and 72 +/- 6%, respectively (each, P less than .05; AMPPCP vs. adenosine, P less than .05). The present data indicate that the negative chronotropic action of ATP is due to its rapid catabolism to adenosine and the action of adenosine at P1-purinoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Effects of adenosine and adenosine 5'-triphosphate on ventricular escape rhythm in the canine heart.

The effects of adenosine and adenosine 5'-triphosphate (ATP) on ventricular escape rhythms were studied in 16 closed chest dogs after electroablation of the His bundle region. All dogs exhibited complete atrioventricular (AV) block and stable ventricular escape rhythm with a mean cycle length of 1,210 +/- 80 ms and a QRS width of 91 +/- 5 ms. Physiologic AV sequential pacing was operative during experiments and was interrupted for rapid (less than or equal to 1 second) administration of either adenosine or ATP (3 mumol/kg) into the right atrium. Adenosine and ATP effectively depressed ventricular escape rhythms in a similar manner both qualitatively and quantitatively (cycle length from 1,210 +/- 80 to 1,764 +/- 132 ms and from 1,274 +/- 84 to 2,000 +/- 150 ms, respectively; each p less than 0.01). These effects were not significantly altered by either physostigmine (an acetylcholinesterase inhibitor) or atropine (a muscarinic cholinergic blocker), but were slightly attenuated by propranolol (a beta-adrenoceptor blocker). In the presence of autonomic blockade, the adenosine transport blocker dipyridamole markedly enhanced the depressant effects of adenosine and ATP. The adenosine competitive antagonist aminophylline reversed the action of dipyridamole. Thus, both adenosine and ATP depress ventricular escape rhythms in vivo, independent of the autonomic nervous system. Moreover, the effects of ATP can be accounted for in large part by its rapid breakdown to adenosine.

Adenosine↗
PubMed1986

Phasic effects of postganglionic vagal stimulation on atrioventricular nodal conduction.

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.

Animals↗
PubMed1986

Vagally induced hyperpolarization in atrioventricular node.

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.

Animals↗
PubMed1986

Effect of postganglionic vagal stimulation on the organization of atrioventricular nodal conduction in isolated rabbit heart tissue.

Postganglionic stimulation of vagal terminals (PGVS) in the isolated rabbit heart atrioventricular (AV) node was used to study the effects of cholinergic influence on AV nodal conduction. Standard microelectrode techniques were used to record action potentials, predominantly from cells located in the N region of the AV node. In addition, programmed stimulation was used in conjunction with PGVS to initiate or terminate AVN reentry. The introduction of a single short burst of PGVS (total duration 50 to 100 msec, impulse duration 1 msec, and interimpulse interval 6 msec) with subthreshold amplitude for AV node fibers caused reproducible disorganization of the prevailing excitation front. This was manifest as local nonuniform depression of conduction, hump formations in the action potentials, and alteration in the sequence of depolarization. The introduction of repetitive bursts of PGVS revealed a triphasic time course of changes in AV nodal conduction time, representing initial maximal prolongation, relative shortening, and secondary inhibition. It was found that these phases corresponded to vagally induced initial disorganization and a subsequent rebound process. Vagally induced disorganization of the sequence of action potential depolarization was also a triggering mechanism for concealed as well as manifest AV nodal reentry. In the latter case the reentry circuit usually involved the AN region and perinodal atrial tissue. PGVS-induced depression of the N region was also able to block the retrograde wavefront, thereby terminating reentry. The possible relationship of PGVS-induced disorganization of conduction and the inhomogeneous structure of AV node are discussed. The present results provide additional information for better understanding of the AV nodal conduction abnormalities observed clinically and particularly those related to AV node-vagus interaction.

Action Potentials↗
PubMed1985

Comparative electrophysiologic effects of adenosine triphosphate and adenosine in the canine heart: influence of atropine, propranolol, vagotomy, dipyridamole and aminophylline.

The electrophysiologic effects of adenosine triphosphate (ATP) and adenosine and the modification of these effects by atropine, propranolol, vagotomy, dipyridamole and aminophylline were studied in a canine model. Both ATP and adenosine exerted transient, dose-dependent negative chronotropic and dromotropic effects on the sinoatrial and atrioventricular nodes, respectively. At all doses tested, the effects of ATP were more pronounced. Treatment with either atropine or propranolol plus bilateral cervical vagotomy attenuated the effects of ATP but not of adenosine. In the presence of propranolol plus vagotomy, both the negative chronotropic and dromotropic effects of ATP and adenosine were enhanced and attenuated in a similar manner by dipyridamole and aminophylline. Thus, when ATP and adenosine are injected rapidly into the right atrium of the intact canine heart, vagal involvement in the mechanism of action of ATP but not of adenosine is mainly responsible for the difference in the magnitude of the electrophysiologic effects of these 2 compounds, and only a small part of the electrophysiologic effects of ATP are the result of its degradation to adenosine.

Adenosine↗
PubMed1985

Adenosine triphosphate and adenosine: perspectives in the acute management of paroxysmal supraventricular tachycardia.

Adenosine triphosphate (ATP) and adenosine exert strong and transient depressant effects on the sinoatrial and atrioventricular (AV) nodes of the human heart. The AV nodal effects of these drugs explain their high efficacy in either terminating AV re-entrant supraventricular tachycardia or in slowing ventricular rate during atrial tachyarrhythmias. Their very short half-life enables repeated administration of increased doses without reaching toxic effects and explains the transient character of their frequent but benign side effects. These agents represent a good alternative to verapamil in the acute management of paroxysmal supraventricular tachycardia both in infants and adults.

Adenosine↗
PubMed1985

Evidence for vagal involvement in the electrophysiologic actions of exogenous adenosine and adenosine triphosphate in the canine heart.

A closed chest canine model was used to study the electrophysiologic effects of adenosine and adenosine triphosphate (ATP) on the sino-atrial (SA) and atrioventricular (AV) nodes. Exogenous adenosine and ATP, when rapidly administered into the right atrium, caused transient negative chronotropic and dromotropic effects on the SA and AV nodes, respectively. These effects reached a maxima in 10-15 sec and dissipated in less than 120 sec. The electrophysiologic effects of ATP were more pronounced than those of adenosine. Physostigmine enhanced the chronotropic effects of adenosine and ATP and the dromotropic effects of ATP. Atropine abolished the enhancement of the electrophysiologic effects of adenosine and ATP caused by physostigmine. In the pentobarbital anaesthetized dog, ATP triggers a vagal reflex which plays a major role in mediating its electrophysiologic effects. Vagal involvement in the electrophysiologic action of adenosine is more modest, but does not appear to be mediated via reflex mechanisms.

Adenosine↗
PubMed1985

A comparative study of the electrophysiologic effects of Striadyne, adenosine triphosphate and adenosine in the canine heart.

The chronotropic and dromotropic effects of the intra-atrial administration of 0.97, 1.93 and 2.90 microM/kg Striadyne, the pharmaceutical form of adenosine triphosphate (ATP) for clinical use, ATP, and adenosine, were compared in 13 anesthetized dogs. Striadyne, ATP and adenosine exerted transient dose-dependent negative chronotropic and dromotropic effects. There was no significant difference between the electrophysiologic effects of Striadyne and ATP which were significantly more pronounced than those of adenosine. Atropine (0.2 mg/kg) significantly attenuated the electrophysiologic effects of 2.90 microM/kg Stridyne and ATP but not those of adenosine. It is concluded that Striadyne and ATP have similar electrophysiologic effects which are more pronounced than those of adenosine mainly due to vagal involvement in their mechanism of action.

Adenosine↗
PubMed1985

Effects of verapamil and bepridil on occlusion and reperfusion arrhythmias in the canine heart.

The effects of verapamil and bepridil on occlusion and reperfusion ventricular arrhythmias including ventricular fibrillation (VF) were studied in a canine model. The control group consisted of 27 dogs. 30 dogs received intravenous verapamil (0.2 mg/kg/3 min followed by a continuous infusion of 0.01 mg/kg/min for 15 min). 18 dogs received bepridil (0.5 mg/kg/min for 10 min). The left anterior descending coronary artery was occluded in one step 8 min after the commencement of verapamil administration and 5 min after the termination of bepridil infusion. The incidence of ventricular arrhythmias during the occlusion period was 14 (VF, 5/14), 13 (VF, 0/13) and 14 (VF, 9/14) in the control, verapamil and bepridil groups, respectively. The frequencies of reperfusion VF were 8/24 (33%), 4/30 (13.3%) and 0/13 (0%), respectively. It was concluded that (a) verapamil effectively prevents occlusion but not reperfusion VF and (b) bepridil has an arrhythmogenic effect in the ischemic canine heart but reduces the incidence of reperfusion VF.

Animals↗