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Biomedical subjects

G R Hageman

Publications and source records attributed to G R Hageman.

At least 37 records · Page 2Linked to original sources
PubMed1986

Differential modulation of autonomic activity by ethmozin and ethacizin (analog of ethmozin) on the canine sinus node and atrioventricular junction.

The chronotropic and dromotropic actions of ethmozin and its diethylamine analog ethacizin were studied in the presence and absence of combined muscarinic, beta- and alpha-adrenoreceptor blockade in the intact canine heart in situ (n = 38). Injections of ethacizin, 5, 10 and 25 micrograms/ml, into the sinus node artery caused an immediate and significant (p less than 0.001) sinus bradycardia of 2, 6 and 11%, respectively. Injection of 25 and 50 micrograms/ml of ethacizin into the atrioventricular (AV) node artery significantly (p less than 0.001) prolonged AV conduction time with occasional second degree heart block. Conduction delay was located exclusively during the AH interval of the His bundle electrogram. Autonomic blockade did not alter the negative chronotropic or negative dromotropic effects of ethacizin. Ethacizin, 25 micrograms/ml, injected into the sinus node artery immediately reduced the sinus node response to vagal stimulations by 30% and the effect of acetylcholine, 0.1 micrograms/ml, injected into the sinus node artery by 50%. Ethacizin, 25 micrograms/ml, injected into the AV node artery immediately reduced the duration of complete AV block elicited by vagal stimulation or intranodal acetylcholine, 0.5 micrograms/ml, by 90%. Ethacizin caused a minor reduction in sinus node response to right stellate stimulations without, however, altering the sinus node response to intranodal norepinephrine. Ethmozin injections of up to 50 micrograms/ml into the sinus and AV node arteries had no chronotropic or dromotropic effects. Ethmozin had a minor and variable vagolytic action but significantly (p less than 0.05) reduced the sinus node response to sympathetic nerve stimulation. Hence, ethacizin, in contrast to ethmozin, has a direct depressing action on both the sinus node and the AV junction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Serial production of controlled periods of temporary heart block used to unmask and assess latent ventricular automaticity during experimental acute myocardial ischemia.

This study examined the onset, time course of development and response to overdrive stimulation of ventricular tachycardia in 10 dogs that underwent a Harris two-stage ligation of the left anterior descending coronary artery. Transient (12 +/- 3 minutes) complete atrioventricular (AV) block was produced 2, 3, 4, 5, 8, 12, 16, 20 and 24 hours after onset of infarction through selective injection of physostigmine salicylate into the AV node artery. Seven of the 10 dogs had early transient arrhythmic episodes that occurred within 20 to 40 minutes after coronary occlusion but none of the dogs had any spontaneous ventricular tachycardia in the ensuing 2 hours. Two hours after left anterior descending coronary artery ligation, complete AV block unmasked in every dog a slow (37 +/- 9 beats/min) AV junctional rhythm readily suppressed by overdrive. Three hours after coronary ligation, AV block revealed a monomorphic ventricular tachycardia (106 +/- 10 beats/min) in 3 of the 10 dogs. Four and five hours after coronary ligation, five and eight dogs, respectively, had ventricular tachycardia during AV block and in three the tachycardia was polymorphic. The two remaining dogs did not develop ventricular tachycardia during the 24 hours of observation. Ventricular tachycardia always began abruptly, first with brief and then longer bursts. Soon after onset the rate of tachycardia began to increase to reach a plateau 2 to 3 hours later at frequencies 21 +/- 9% greater than the initial tachycardia rate. Concomitant with this increase in rate there was a steady decline of overdrive suppressibility and during the plateau phase there was little or no overdrive suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Atrioventricular junctional tachycardia during heart block.

The response of the atrioventricular (AV) junction to brief intense adrenergic stimulation applied during episodes of second degree heart block achieved by acetylcholinesterase paralysis in the AV junction was examined in six dogs. Despite profound depression of AV conduction due to enhanced cholinergic activity, strong local adrenergic stimulation still readily elicited AV junctional tachycardia. Increase in cholinomimetic influences in the AV junction did not prolong transatrial or His bundle-ventricular conduction times. During AV junctional rhythm and retrograde atrial capture (n = 4), neither the sequence of retrograde atrial activation nor the atrial electrogram configurations were altered. In the two remaining dogs the AV junctional tachycardia was associated with AV dissociation. These findings suggest that the acetylcholine-induced depression of AV conduction is located in the AV node region exclusively. More important, however, is the demonstration that retrograde atrial activation originating from a pacemaker located in the AV node or immediate vicinity could actually precede the inscription of the H spike by a considerable amount of time, further suggesting that anterograde conduction from the pacemaker site to the bundle of His is far more depressed by acetylcholine than is the concomitant retrograde conduction from the pacemaker site to the atrium. Thus, inference of the origin of a subsidiary pacemaker from the P wave configuration or the relation of the A wave to the His bundle electrogram, or both, may lead to erroneous conclusions.

Animals↗
PubMed1986

Differential sympathetic-parasympathetic interactions in sinus node and AV junction.

This study examined the effects and interactions evoked by various combinations of parasympathetic (P) and sympathetic (S) stimulations on sinus node automaticity and atrioventricular (AV) conduction (both anterograde and retrograde) in 11 two-mo old anesthetized puppies. The respective effects of these autonomic maneuvers were assessed by covariant analysis using a linear regression model of the form Y = alpha 0 + alpha 1 X base line + alpha 2 X sequence + alpha 3 X S + alpha 4 X S2 + alpha 5 X P + alpha 6 X P2 + alpha 7 X (P X S).... The effects of parasympathetic and sympathetic stimulation, of the quadratic term S2, and of the interaction term (P X S) were highly significant (P less than 0.0001) on both sinus node automaticity and AV conduction (anterograde and retrograde). In contrast, the effect of the quadratic term P2 was significant on sinus node automaticity only. Sequence of stimulation whether (SP) or (PS) had no significant effect on either chronotropic or dromotropic properties. Furthermore, whereas augmented antagonism with parasympathetic predominance over sympathetic activity was readily demonstrable in the control of sinus rate, the reverse, i.e., augmented antagonism with sympathetic preponderance over parasympathetic activity, was found to apply to the control of AV conduction (both anterograde and retrograde). Hence, the nature and extent of parasympathetic-sympathetic interactions vary considerably, depending on which cardiac structure and/or function is under scrutiny. It appears that AV conduction is especially sensitive to modulation of sympathoadrenergic activity, whereas sinus node automaticity is particularly responsive to cholinomimetic influences.

Animals↗
PubMed1986

Cardiac autonomic efferent activity during baroreflex in puppies and adult dogs.

Blood pressure and heart rate were recorded in 15 anesthetized puppies (6-10 wk, 1-6 kg) and 18 adult mongrel dogs (greater than 1 yr, 18-26 kg) before and during acute blood pressure changes achieved with nitroglycerin or phenylephrine (4 and 8 micrograms/kg iv). Overall heart rate responses to blood pressure changes in adults were significantly (P less than 0.05) greater than those in puppies. Following control baroreflex responses, two multifiber efferent preparations from the discrete thoracic cardiac nerves (sympathetic, n = 48; parasympathetic, n = 18) were simultaneously recorded and analyzed by microprocessor. Severing of the nerves significantly attenuated the heart rate responses to blood pressure changes in puppies only, suggesting less redundancy of the neural regulation of the sinus node in the puppy. The pressure-induced reflex changes in the sympathetic or parasympathetic efferent nerve activities were not significantly different between adult dogs and puppies. There were no significant differences in reflex activities in right-sided (n = 29) vs. left-sided (n = 19) sympathetic nerves in either puppies or adult dogs. Preganglionic sympathetic fibers in puppies (but not adult dogs) were more responsive to blood pressure changes than were postganglionic sympathetic fibers. Thus baroreceptor reflex control in the puppy is less developed than in the adult canine heart, and the maturational difference in neural regulation of the heart is at or beyond the efferent nerve terminals.

Aging↗
PubMed1986

Effects of the diethylamino analog of ethmozin (ethacizin) upon sympathetic and parasympathetic efferent activity to the canine heart.

This study examined the effects of the diethylamino analog of ethmozin (ethacizin) (1 mg/kg i.v.) on the spontaneous and reflexly elicited efferent activity in thoracic cardiac sympathetic and parasympathetic nerves. Nitroglycerin and phenylephrine (4 and 8 micrograms/kg i.v.) were administered to 15 anesthetized mongrel dogs while monitoring blood pressure and heart rate. In each dog two cardiac nerves were isolated and efferent neurograms were recorded simultaneously and analyzed by microprocessor. Ethacizin significantly attenuated the spontaneous sympathetic efferent activity in both left and right, preganglionic (n = 8) and postganglionic (n = 14) sympathetic nerves to the heart. In contrast, reflex changes in sympathetic activity elicited by baroreceptor challenges were not affected by ethacizin. Also, ethacizin did not significantly affect either spontaneous or baroreceptor reflex-induced parasympathetic efferent activities in eight preganglionic nerves. Thus, this new phenothiazine derivative may exert part of its antiarrhythmic action through a reduction of the spontaneous sympathetic tonic discharges to the heart. The fact that ethacizin reduced neither the reflex-induced changes in sympathetic or parasympathetic activities nor influenced the tonic vagal discharges further suggests that the compound is not likely to interfere with reflexly mediated cardiovascular adaptive changes.

Animals↗
PubMed1986

[Action of ethacizin on normal and anomalous forms of Purkinje fiber automaticity in the dog].

The effect of a new anti-arrhythmic drug etacysin was studied in various forms of dog Purkinje's fibres automativity: normal and abnormal arising at a late stage of experimental myocardial infarction (24 hrs after coronary artery ligation) and induced by ions Ba2+. An average 57% decrease in the frequency of automaticity of normal Purkinje's fibres due to steepening the slope of slow diastolic depolarization and almost complete depression of an abnormal one was observed for the drug concentrations 5 X 10(-7) and 10(-6) g/ml. Reduced automaticity was also related to decreased slow diastolic depolarization. Maximal values of diastolic potential were found unchanged.

Animals↗
PubMed1985

Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction.

The direct effects of alinidine (N-allyl-clonidine) on the sinus node and atrioventricular (AV) junction were studied in 18 anesthetized dogs. Stimulus frequency-response curves to right stellate ganglion and right cervical vagus stimulations as well as responses to norepinephrine or acetylcholine were determined before and after selective perfusion of alinidine into the sinus node artery. Alinidine (1 microgram/ml) had no effect on spontaneous sinus rate [148 +/- 5 (SE) beats/min]. However, alinidine concentrations of 5, 10, and 25 micrograms/ml produced significant (P less than 0.05) sinus slowing to 138, 127, and 121 beats/min, respectively. Recovery to control rate was dose dependent and took from 4 to 33 min. Sinus rate increases with right stellate stimulations were not affected by alinidine. However, sinus rate decreases with right vagal stimulations were significantly (P less than 0.01) attenuated by alinidine. The negative chronotropic effects of acetylcholine were not influenced by alinidine. Alinidine (1-100 micrograms/ml into AV node artery) had no effect on the A-H interval of the His bundle electrogram. However, alinidine (10 and 25 micrograms/ml) diminished the AV block produced by stimulation of the left vagus in electrically paced hearts but not the negative dromotropic actions of directly administered acetylcholine. Thus alinidine has direct negative chronotropic effects, no effect on sinus node responses to sympathetic stimulation, ability to diminish sinus node and AV junctional responses to vagal stimulations without interference at the cholinergic muscarinic receptor, and 4) no effect on AV nodal conduction.

Acetylcholine↗
PubMed1985

Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.

Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle lengths. Data relating recovery times and return to control conditions to prepacing cycle length, pacing cycle length, duration of pacing, site of pacing, and origin of rhythms were analyzed by covariance analysis. From the analyses, the relative contribution of the determinants are: the prepacing cycle length 73%, the site of pacing 3.5%, the pacing cycle length 2%, and the interaction of the site of pacing and pacing cycle length 1% for sinus node recovery time; and for slow atrioventricular junctional rhythm recovery time, the duration of pacing 40%, the interactions between the duration of pacing and the pacing cycle length 27%, and the prepacing cycle length 9%. A modified exponential decay model predicted 8 beats for return to prepacing conditions during sinus rhythm and 66-100 beats during atrioventricular junctional rhythm. We conclude that the single most important determinant of sinus node recovery time is the prepacing cycle length. Pacing cycle length and site of pacing have a significant but small influence on sinus node recovery time and duration of pacing, beyond 20 seconds, has no significant influence. In contrast, duration of pacing is the most important determinant of slow atrioventricular junctional recovery time. Another major determinant of slow atrioventricular junctional recovery time is the interactions between pacing cycle length and duration of pacing. Prepacing cycle length has a minor influence, and site of pacing has no influence, on slow atrioventricular junctional recovery time.

Animals↗
PubMed1984

Parasympathetic and sympathetic efferent traffic during a cardiogenic hypertensive chemoreflex.

Activation of a cardiac chemoreceptor with serotonin elicits a reflex which includes changes in heart rate, contractile force, regional blood flow and hypertension. In six anaesthetised dogs we simultaneously recorded parasympathetic and sympathetic efferent traffic elicited during this cardiogenic reflex. The parasympathetic fibres were confirmed by reciprocal frequency changes with changes in blood pressure. The sympathetic fibre activity (anterior ansa subclavia) was attenuated or eliminated by ganglionic blockade or by clonidine. Whereas the phasic sympathetic multifibre discharge was only followed by a quiet period, the parasympathetic multifibre discharge was both preceded and followed by a quiet period. The sympathetic discharge preceded the parasympathetic discharge by 683 +/- 170 ms. These autonomic efferent discharges were not elicited by administration of serotonin into the carotid artery, but were abolished by pretreatment with the serotonin antagonist, cyproheptadine. Cyproheptadine blockade could be overcome by increasing the serotonin concentration tenfold. This remarkable neural asynchrony has important implications concerning the electrical stability of the heart.

Animals↗
PubMed1984

Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog.

Studies from our laboratory suggest that the afferent renal nerves from the clipped kidney enhance sympathetic nervous system activity in established one-kidney, one clip and two-kidney, one clip Goldblatt hypertension. Because adenosine is released during renal ischaemia and adenosine has been shown to increase the frequency of afferent renal nerve signals, we proposed the hypothesis that intrarenal adenosine might produce hypertension by activating the sympathetic nervous system via the afferent renal nerves. To examine this hypothesis, changes in arterial pressure and activity of the sympathetic nervous system were measured during renal artery infusion of adenosine before and after renal denervation in uninephrectomized sodium replete conscious dogs. Intrarenal adenosine infusion produced a 21 +/- 3 mmHg mean arterial pressure rise in association with an increase in plasma norepinephrine. Ganglionic blockade during intrarenal adenosine infusion resulted in a significantly greater decrease in arterial pressure compared to control responses. After renal denervation, intrarenal adenosine infusion resulted in no change in arterial pressure, plasma norepinephrine or arterial pressure response to ganglionic blockade. To further assess sympathetic activity changes, right renal norepinephrine secretion and multifibre efferent neural traffic were measured during left renal artery adenosine infusion in alpha-chloralose-anaesthetized dogs. Left renal artery adenosine infusion resulted in increased right renal vascular resistance in association with increased renal norepinephrine secretion and increased efferent neural activity. The data indicate that in the dog with intact renal nerves, intrarenal adenosine produces hypertension by activating the sympathetic nervous system.

Adenosine↗
PubMed1983

Studies of changes in breathing and blood pressure accompanying a cardiogenic hypertensive chemoreflex compared in conscious and anesthetized dogs.

Serotonin activates a cardiogenic hypertensive chemoreflex characterized by sudden hypertension. This study in 16 awake and 12 anesthetized dogs was conducted to examine the influence of changes in breathing or heart rate as they may influence the reflex hypertension. In all 28 dogs, either anesthetized or awake, there is a variable but brief initial reflex bradycardia and in all dogs there is transient ventilatory stimulation, but the response in every dog was characterized by hypertension within at most 10 seconds after administering serotonin. Treatment with atropine regularly eliminated the reflex bradycardia and caused the hypertension to appear soon (average of 6 seconds to maximal level). Atropine did not alter the reflex stimulation of breathing. Since atropine eliminated any transient bradycardia (and associated hypertension) but did not prevent reflex changes in breathing, we do not believe that breathing alteration plays any significant hemodynamic role in this reflex.

Afferent Pathways↗
PubMed1983

Influence of atrial mechanoreceptors upon the sympathetic efferent activity elicited during a cardiogenic chemoreflex in the dog.

Two different cardiogenic reflexes were studied for their effects upon the activity recorded from the thoracic cardiac nerves of 7 chloralose-anesthetized dogs. Sympathetic efferent activity in 5 right and 7 left anterior ansa multifiber preparations was quantitatively analyzed. A cardiogenic hypertensive chemoreflex was induced by administration of serotonin (100 micrograms/ml, 2 ml) into the left atrium before, during and after inflation of balloons in the right and/or left atrial appendages. Balloon inflations alone resulted in heart rate increases of 5-20 bpm but arterial blood pressure, pulse pressure and end diastolic pressure were not significantly affected. Control serotonin-induced efferent discharges were 174 +/- 10% (mean +/- S.E.M.) of resting activity with a duration of 5.2 +/- 0.4 s. During inflation of both atrial balloons, the serotonin-induced efferent discharges were 165 +/- 14% (N.S.) of resting activity with a duration of 7.8 +/- 0.7 s (P less than 0.01). Following release of the balloons, the serotonin-induced discharges were 152 +/- 17% (N.S.) of resting activity with a duration of 4.9 +/- 0.4 s (N.S.). These results suggest that afferent signals from atrial mechanoreceptors can act to increase the duration but not the total intensity of the efferent sympathetic discharges elicited during a cardiogenic chemoreflex.

Animals↗
PubMed1983

Effects of gamma-aminobutyric acid on neural regulation of the canine sinus node.

The direct effects of gamma-aminobutyric acid (GABA) on the sinus node and its neural regulation were studied by selective perfusion of the sinus node artery (SNA) in 26 open-chest pentobarbital-anesthetized dogs. GABA (1-1,000 micrograms/ml, 2 ml, SNA) produced no direct effect on intrinsic sinus rate, but in several experiments (at 1 microgram/ml) it produced an inconsistent augmentation of the sinus tachycardia due to right stellate stimulation. At all other concentrations tested (10-1,000 micrograms/ml), GABA did not significantly alter the sinus node response to stellate stimulation. Local alpha-receptor blockade with phentolamine or muscarinic receptor blockade with atropine through the SNA prior to the perfusion of GABA did not change the sinus node responses. GABA (10-1,000 micrograms/ml, 2 ml, SNA) significantly attenuated (by 45-80% of control) the sinus bradycardia due to stimulation of the right vagosympathetic trunk. The sinus node response to selective perfusion of norepinephrine or acetylcholine (0.01 micrograms/ml, 2 ml, SNA) was not affected by GABA. The stellate augmentation (when present) and vagal attenuation were both antagonized by perfusion of picrotoxin (1,000 micrograms/ml, 2 ml, SNA). It is concluded that GABA does not exert any direct effect on the sinus node but may indirectly influence sinus rate by an effect on local nerves or ganglia.

Animals↗
PubMed1980

Reflex heart block. Baroreflex, chemoreflex and bronchopulmonary reflex causes.

Reflex heart block was studied in 20 dogs anesthetized with sodium pentobarbital and in 5 trained unanesthetized dogs. Three different vagal reflexes were produced: the Marey response during hypertension caused by administering methoxamine, a cardiogenic hypertensive chemoreflex activated by injection of serotonin into the left atrium and the Hering-Breuer reflex observed during normal respiration of unanesthetized dogs. In every dog during any of the three reflexes heart block was consistently observed after the normal slowing response of the sinus node had been selectively eliminated by the direct perfusion of 10 microgram of atropine into the sinus node artery. This was a uniform response despite its being variously produced by a pressor reflex, a chemoreflex or an extracardiac bronchopulmonary reflex. Transient heart block is therefore to be anticipated during reflexes with vagal efferent components if for any reason the sinus node is incapable of slowing suitably. The possible clinical relevance of these experimental observations is discussed.

Animals↗
PubMed1980

Analysis of sympathetic discharges during cardiogenic hypertensive chemoreflex.

Serotonin activates a cardiogenic hypertensive chemoreflex. During this reflex, sympathetic efferent neural discharges were examined in 10 anesthetized dogs. Thoracic nerves were identified, severed distally, and placed across electrodes. The efferent neurogram was recorded along with an electrocardiogram and blood pressure and stored on tape. Neurograms were later analyzed by a Lab 8/e computer with a Schmitt trigger. The resting tone and the elicited discharges of the multifiber preparations were plotted as poststimulus histograms. The integrals of the histograms were normalized. During the reflex, sympathetic efferent discharges averaged 4.9 (+/- 0.8) s in duration and the total discharge frequency was 199 (+/- 16)% of control tone. The evoked peak blood pressure response averaged 221/171 mmHg. Following autonomic blockade, the attenuated blood pressure response averaged 125/96 mmHg. The sympathetic efferent discharges then lasted 5.2 (+/- 0.7) s (NS). However, total discharge frequency (268 +/- 37% of control tone) was significantly greater (P less than 0.01) that before autonomic blockade. These data suggest that baroreceptors influence the rate of discharge and the total amount of neural traffic, but not the duration of the sympathetic response evoked by the cardiogenic hypertensive chemoreflex.

Animals↗