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Biomedical subjects

G R Hageman

Publications and source records attributed to G R Hageman.

At least 55 records · Page 3Linked to original sources
PubMed1979

Chronotropic and dromotropic effects of histamine on the canine heart.

The actions of 2-methylhistamine (H1 agonists), 4-methylhistamine (H2 agonist), and histamine were studied by selective perfusion of the sinus node artery and atrioventricular node artery in 75 dogs anesthetized with pentobarbital sodium. 2-Methylhistamine and histamine had variable and inconsistent effects on the sinus rate. 4-Methylhistamine (100 microgram/ml) produced acceleration of the sinus rate from 158 +/- 4 to 173 +/- 5 beats per minute (P less than 0.05) when perfused via the sinus node artery. The effects of the histamine agonists on atrioventricular junctional rhythms were similar to the effects on sinus rhythm. The response of the sinus node to vagal stimulation was attenuated by selective perfusion with histamine; however, the direct negatively chronotropic action of acetylcholine was not affected by histamine. Neither 2-methylhistamine nor 4-methylhistamine affected the response of the sinus node to vagal stimulations. Both 4-methylhistamine and histamine (but not 2-methylhistamine) attenuated (P less than 0.05) the response of the sinus node to stimulation of the right stellate ganglion. The positively chronotropic effects of directly perfused norepinephrine were unaffected by histamine or 4-methylhistamine. These results suggest a neural depressing action of histamine on autonomic efferent fibers. In the atrioventricular junction, both histamine and 2-methylhistamine (but not 4-methylhistamine) had negatively dromotropic effects. Cimetidine (an H2 antagonist) had no significant direct effects on the sinus rate or atrioventricular conduction and failed to prevent the acceleration of the sinus rate produced by local perfusion with 4-methylhistamine.

Acetylcholine↗
PubMed1978

Neural pathways of a cardiogenic hypertensive chemoreflex.

Excitation of a cardiac chemoreceptor with 5-hydroxytryptamine (serotonin) produces a complex autonomic reflex which includes hypertension, changes in heart rate and contractile force, and disturbances of AV conduction. This study examines the afferent and efferent neural pathways of this autonomic reflex in 60 anesthetized dogs. We used cooling and sectioning techniques in 40 of these, and in 20 others recorded afferent neurograms. The most common afferent pathways for the reflex were found in the left and right recurrent cardiac nerves. No preferential efferent routes to the heart were found, although the nature of the reflex cardiac response could be altered by specific nerve interruption. Cyproheptadine (1 mg/kg iv) regularly abolished both the reflex and the chemoreceptor afferent neural traffic, but injection of a 10 times higher concentration of serotonin (1 mg/ml) readily surmounted the blockade and restored the chemoreceptor neural traffic. Thus cyproheptadine interdicts the reflex at the site of its initiation.

Afferent Pathways↗
PubMed1978

Hemodynamic components of a cardiogenic hypertensive chemoreflex in dogs.

The mechanical and hemodynamic components of a cardiogenic hypertensive chemoreflex were studied in 50 dogs. Within 6 seconds after a single injection of serotonin (100 microgram/ml) into the left atrium, mean pressure (mm Hg) rose in the aorta from 103 to 197 and in the pulmonary artery from 21 to 34. Left ventricular dp/dt virtually doubled. There was an increase (75%) in peripheral vascular resistance that returned to control within 10 seconds. There was no significant change in pulmonary vascular resistance. Aortic and pulmonary arterial hypertension were associated with a profound depression (82%) in atrial force. Atropine transformed this negative inotropic effect on the atria into a positive inotropic action that averaged 65%. In contrast, ventricular force was always sharply increased, more in the right (95%) than in the left ventricle (50%). Bilateral stellectomy did not eliminate the reflex but it completely abolished the initial increase of cardiac contractility; a delayed increase in contractility persisted and was due exclusively to release of catecholamines from the adrenal glands. This cardiogenic hypertensive chemoreflex uses the vagus for its afferent neural traffic and both the sympathetic and the vagus nerves for its efferent route. The brief and intense systemic vasoconstriction concomitant with an increase in cardiac contractility might represent a kind of "aortic cough." Some possible clinical implications are discussed.

Adrenal Medulla↗
PubMed1977

Differential sensitivity to neurotransmitters in denervated canine sinus node.

This investigation determined the chronotropic effects of norepinephrine and acetylcholine (ACh) administered selectively into the canine sinus node artery after cardiac denervation. In 42 dogs the cervical vagi were isolated, the heart was exposed, and vagal stimulations were performed before and after sham procedure or extrinsic cardiac parasympathectomy. Four additional dogs underwent bilateral stellectomy. The dogs were reanesthetized 4-23 days later, and blood pressure, heart rate, ECG, and local cardiac electrograms were recorded. The vagi were again stimulated and the effectiveness of the parasympathectomy was verified in 11 of the dogs. On selective perfusion of the sinus node with 0.001- to 1-microgram doses of ACh, the sinus bradycardias of the parasympathectomized and the sham-operated dogs were not significantly different. The responses to norepinephrine (0.01 and 0.1 microgram/ml) administered via the same route in the stellectomized dogs were significantly greater than those in the sham-operated dogs, thus verifying this technique for the assessment of sinus node sensitivity to neurotrasmitters. We conclude that extrinsic denervation of the canine sinus node leads to development of a differential response between adrenergic and cholinergic neurotransmitters. These differential sensitivities may be important when considering the pharmacological responses and electrical stability of the denervated and/or transplanted heart.

Acetylcholine↗
PubMed1977

Chronology and mode of reinnervation of the surgically denervated canine heart: functional and chemical correlates.

This study was undertaken to evaluate functionally the time and pattern of inotropic and chronotropic efferent cardiac reinnervation of the deneravated canine heart and to correlate functional data with regional myocardial catecholamine content and supersensitivity to norepinephrine. Our data indicate that efferent autonomic reinnervation takes place first in the atria, followed by a base-to-apex sequence in the ventricles, and that such reinnervation is functionally effective 9-12 mo after denervation. The return of neural function parallels the return of measurable quantities of myocardial norepinephrine and is accompanied by a decrease in supersensitivity to exogenous norepinephrine. The return to apparently complete functional reinnervation, however, cannot be quantitatively related to myocardial levels of catecholamine. Segmental myocardial supersensitivity to norepinephrine is sequentially reversed during progressive adrenergic reinnervation.

Adrenergic Fibers↗
PubMed1976

Cardiac dysrhythmias in the conscious dog after surgically induced autonomic imbalance.

The ventrolateral cardiac nerve in the dog is a primary branch of the left sympathetics and represents a direct neural link between the central nervous system and the heart. Its electric excitation elicits characteristic shifts in pacemaker and tachydysrhythmias related to its explicit innervation of the inferior atrial, atrioventricular (A-V) junctional and ventricular tissues. Total denervation of the canine heart, sparing the ventrolateral cardiac nerve, produced a long-term model in which only these portions of the heart retained their sympathetic innervation. The trained unanesthetized model dog was subjected to severe exercise in order to determine the effects of elevated levels of sympathetic tone upon these important regions of the conduction system. Reproducible tachydysrhythmias were elicited in all six animals completing the regimen of periodic testing over a period of 136 to 378 days after operation. The abnormal rhythms consisted of shifting cardiac pacemakers and supraventricular A-V junctional and ventricular tachycardias with frequent premature systoles. Comparable abnormalities were not observed in a similarly tested sham-operated animal or in dogs with a totally denervated heart. The exercise-induced dysrhythmias gradually disappeared with time, presumably in relation to autonomic reinnervation of the heart. The characteristic patterns of ventrolateral cardiac nerve and upon its presumed influence upon Purkinje fiber and A-V nodal automaticity and temporal dispersion of refractoriness in myocardial tissues.

Animals↗
PubMed1976

Autonomic neural control of cardiac rhythm: the role of autonomic imbalance in the genesis of cardiac dysrhythmia.

Cardiac dysrhythmias result from abnormalities in rate, regularity, or sequence of cardiac activation, and because of direct actions of the autonomic nervous system upon each of these properties, imbalance in this system may play an important role in the genesis of cardiac dysrhythmia. A canine model has been developed in which the extrinsic innervation of the heart is ablated with the exception of the ventrolateral cardiac nerve. This nerve is distributed primarily to the inferior atrial, AV junctional, and ventricular tissues. Following recovery from surgery, the animal is placed on a treadmill and required to perform strenuous exercise. In all of six animals which sustained repeated exercise testing over periods of 4-12 months, dysrhythmias of varying complexities were elicited. None appeared in parallel experiments conducted in control or sham-operated animals. The dysrhythmias consisted of supraventricular, AV junctional, or ventricular tachycardias with occasional premature atrial or ventricular systoles. The dysrhythmias were not influenced by atropine but were generally controlled by propranolol.

Animals↗
PubMed1975

Direct and reflex cardiac bradydysrhythmias from small vagal nerve stiumaltions.

Alterations in cardiac pacemaker location, its rate of discharge, and A-V conduction patterns were induced in anesthetized adult dogs by electrical stimulation of the thoracic vagi and their small cardiac branches before and after cervical vagotomy. Electrical activity from small, contiguous bipolar silver electrodes was amplified and recorded by an optical oscillograph. The electrodes were located over the SA node, the three internodal pathways, the left atrium, and ventricular epicardium. A hoffman-type plaque electrode was placed over the A-V node to record a His bundle electrogram simultaneously with a Lead II electrocardiogram. Electrical stimulation of the intact left recurrent laryngeal nerve and its cardiac branches before and after vagotomy induced both direct and reflex effects on SA nodal cycle length. Efferent dromotropic effects on the A-V node varied from first- to third-degree heart block during stimulation of individual left recurrent cardiac branches. Stimulation of the right recurrent cardiac nerve induced atrial bradycardia with heart block above the His bundle. Stimulation of individual right vagal branches near the heart induced bradycardia, cardiac asystole, shifts in atrial pacemaker location, or activation of His pacemakers. Establishment of the His rhythm probably indicates selective inhibition of supraventricular but not of the His bundle. Asystole and His rhythms induced during stimulation of the more caudal branches of the right cardiac vagal nerves were generally reflexly mediated and were abolished by cervical vagotomy.

Animals↗
PubMed1975

Selective parasympathectomy of the heart.

Attempts to devise a chronic animal model with parasympathetic cardiac denervation have been complicated by early mortality due to pulmonary and esophagogastric dysfunction. By use of surgical techniques confined to the intrapericardial left atrium and immediately adjacent vena cava, selective cardiac parasympathectomy was performed on dogs. Verification of denervation was performed at the time of surgery by electrical stimulation of the cervical and thoracic vagi and stellate ganglia while recording blood pressure, ECG, and atrial and ventricular contractile force. Results demonstrate complete efferent parasympathetic denervation and abolition of the Bezold-Jurish reflex. Tachycardia at approximately 140/min was noted in all animals immediately and for several weeks postoperatively. No extracardiac complications were noted in any of the animals subjected to this procedure. Right heart catheterization of the conscious sedated dog revealed no evidence of right heart failure. Evidence of parasympathetic efferent reinnervation (sinus arrhythmia) was seen in some animals. This preparation should prove useful in studies of parasympathetic control of the heart, coronary vessels, and cardiovascular reflexes.

Animals↗
PubMedDate not supplied

Differential effects of sympathetic activity on AV junctional automaticity and AV conduction.

Rapid ventricular response during episodes of supraventricular tachycardia are often followed, on abrupt cessation of the tachycardia, by prolonged pauses terminated by a sluggish and sometimes erratic escape of a supraventricular pacemaker. Such chronotropic-dromotropic paradoxes are readily reproduced in the animal laboratory following elimination of the sinus node and bilateral decentralization of the stellate ganglia and vagi. This study examined whether left stellate stimulation (0.5, 1, 2, 4, 8 and 16 Hz) or lack thereof differentially affected AV junctional automaticity and AV conduction. In the absence of any sympathetic neural activity (maximal sympathetic deficit), the AV junctional rate averaged a mere 22 +/- 2 percent of its peak performance, whereas under the same conditions, anterograde AV conduction averaged 73 +/- 5 percent and retrograde VA conduction 56 +/- 13 percent of their respective peak performances. On comparing the response curve (normalized responses) for AV junctional automaticity with that obtained for anterograde AV conduction the differences were significant at all frequencies between 0 and 4 Hz. Retrograde VA conduction (as assessed by the fastest ventricular pacing rate still conducted 1:1 to the atria) was always significantly less than anterograde AV conduction (as assessed by the fastest atrial pacing still conducted 1:1 to the ventricles). These results indicate that AV junctional automaticity is considerably more affected by sympathetic deficit than are either anterograde or retrograde AV conduction. In other words, AV junctional automaticity is far more dependent upon sympathetic input than AV conduction. While sympathetic influence is critical to the escape and maintenance of AV junctional automaticity both anterograde and retrograde AV conduction are remarkably resilient even under conditions of severe sympathetic deficit.

Animals↗