Biomedical subjects

G R Hageman

Publications and source records attributed to G R Hageman.

At least 19 recordsLinked to original sources

PubMed2001

Angiotensin II modulates catecholamine release into interstitial fluid of canine myocardium in vivo.

This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine (EPI)] into the cardiac interstitial fluid (ISF) space of dogs with adrenals intact (AI) (n = 7) and with adrenals clamped (AC) (n = 5). LV ISF samples were collected at 3-min intervals during administration of ANG II (100 microM ANG II at 1 ml/min for 10 min) to right atrial neurons via their local arterial blood supply and during electrical stimulation of the stellate ganglia of open-chest anesthetized dogs. In AI dogs, ANG II caused ISF NE to increase fivefold (P < 0.05) without a significant increase in coronary sinus (CS) NE. Electrical stimulation (5 ms, 4 Hz, 8-14 V, and 10 min) of the stellate ganglia caused a similar increase in ISF NE (P < 0.05), accompanied by a sevenfold increase in CS NE (P < 0.05). ISF EPI increased greater than sixfold during ANG II infusion (P < 0.05) and during stellate stimulation. However, during ANG II infusions, aorta plasma EPI levels increased fourfold in AI dogs, whereas in AC dogs, CS NE and EPI levels were unaffected during ANG II infusions. Nevertheless, baseline ISF NE and EPI did not differ and increased to a similar extent during ANG II infusions in AI versus AC dogs. Thus exogenously administered ANG II increases the amount of NE liberated into the ISF independent of the adrenal contribution, the amount matching that induced by electrical stimulation of all cardiac sympathetic efferent neurons. In contrast, NE spillover into the CS occurred only during electrical stimulation of stellate ganglia. NE release and uptake mechanisms within the myocardium are differently affected, depending on how the final common pathway of the sympathetic efferent nervous system is modified.

Angiotensin II↗

PubMed1999

Evidence for angiotensin-converting enzyme- and chymase-mediated angiotensin II formation in the interstitial fluid space of the dog heart in vivo.

BACKGROUND: We have previously demonstrated that angiotensin II (Ang II) levels in the interstitial fluid (ISF) space of the heart are higher than in the blood plasma and do not change after systemic infusion of Ang I. In this study, we assess the enzymatic mechanisms (chymase versus ACE) by which Ang II is generated in the ISF space of the dog heart in vivo. METHODS AND RESULTS: Cardiac microdialysis probes were implanted in the left ventricular (LV) myocardium (3 to 4 probes per dog) of 12 anesthetized open-chest normal dogs. ISF Ang I and II levels were measured at baseline and during ISF infusion of Ang I (15 micromol/L, n=12), Ang I+the ACE inhibitor captopril (cap) (2.5 mmol/L, n=4), Ang I+the chymase inhibitor chymostatin (chy) (1 mmol/L, n=4), and Ang I+cap+chy (n=4). ISF infusion of Ang I increased ISF Ang II levels 100-fold (P<0.01), whereas aortic and coronary sinus plasma Ang I and II levels were unaffected and were 100-fold lower than ISF levels. Compared with ISF infusion of Ang I alone, Ang I+cap (n=4) produced a greater reduction in ISF Ang II levels than did Ang I+chy (n=4) (71% versus 43%, P<0.01), whereas Ang I+cap+chy produced a 100% decrease in ISF Ang II levels. CONCLUSIONS: This study demonstrates for the first time a very high capacity for conversion of Ang I to Ang II mediated by both ACE and chymase in the ISF space of the dog heart in vivo.

Angiotensin II↗

PubMed1997

Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces.

Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.

Angiotensin I↗

PubMed1996

Posterior left thoracic cardiac sympathectomy by surgical division of the sympathetic chain: an alternative approach to treatment of the long QT syndrome.

Although high thoracic left sympathectomy via an anterior surgical approach is a highly efficacious treatment for refractory ventricular arrhythmias in patients with the long QT syndrome, the degree of sympathetic denervation has been variable, success of the operation is influenced by anatomical differences between patients, and Horner's syndrome may result. We hypothesized that interruption of sympathetic input to the heart could be accomplished using a posterior thoracic approach to this variable and often complex anatomy by division of the sympathetic chain rather than by direct destruction of the stellate and superior thoracic ganglia with the more conventional anterior, supraclavicular approach. In addition, the posterior approach should decrease the risk of Horner's syndrome by avoiding the ocular sympathetic efferent nerves. This posterior approach is described in five patients with the long QT syndrome and recurrent ventricular arrhythmias. After a mean follow-up of 18 +/- 12 months, all are alive without Horner's syndrome.

Adult↗

PubMed1996

Angiotensin II formation in dog heart is mediated by different pathways in vivo and in vitro.

Angiotensin-converting enzyme (ACE) inhibitors (I) have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. However, in vitro assays in human heart extracts have demonstrated that > 75% of ANG II-forming enzyme activity was not inhibited by captopril (Cap) and therefore did not appear to be related to ACE but was inhibited by chymostatin, suggesting that it was predominantly chymase-like activity. Previous work in our laboratory has demonstrated a similar relative contribution of ACE and chymase-like activity toward ANG II formation in vitro in dog heart tissue extracts. Accordingly, we compared Cap-inhibitable ANG II formation in vitro in heart tissue of five adult mongrel dogs to the in vivo Cap-inhibitable, ANG II-forming activity across the myocardial bed in four openchest, adult mongrel dogs. In vitro studies demonstrated that only 6 +/- 2% of ANG II formation was inhibited by Cap from heart tissue extracts of the left ventricular midwall. In in vivo studies, ANG I (0.5 nmol/min) followed by ANG I plus the ACE inhibitor Cap (0.1 mumol/min) was infused into the left anterior descending artery, and ANG II was assayed in the proximal aorta and coronary sinus. The arterial-venous (A-V) difference of ANG II across the myocardial circulation increased significantly during ANG I infusion (-13.4 +/- 23.5 to 142.8 +/- 71.4 pg/ml; P < 0.03). Subsequent coinfusion of Cap with ANG I significantly decreased the myocardial A-V difference of ANG II by 60 +/- 18% (P < 0.05). Thus, in contrast to the in vitro situation, ANG II formation in vivo is inhibited significantly by Cap in the normal dog heart. This comparison of in vivo and in vitro conversion of ANG I to ANG II by ACE and chymase-like activity suggests that in vitro assays may underestimate the functional contribution of ACE to intracardiac ANG II formation.

Angiotensin I↗

PubMed1995

23Na and 31P nuclear magnetic resonance studies of ischemia-induced ventricular fibrillation. Alterations of intracellular Na+ and cellular energy.

To clarify the role of Na+i, pHi, and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricular fibrillation (VF), interleaved 23Na and 31P nuclear magnetic resonance spectra were collected on perfused rat hearts during low-flow ischemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hearts from normal (sham) rats and 89% of the hypertrophied hearts from aorticbanded (band) rats (P < .01 versus sham) exhibited VF. Phosphocreatine content was significantly higher in sham than band hearts during control perfusion (53.3 +/- 1.6 versus 39.8 +/- 2.0 mumol/g dry wt). Before VF at 20 minutes of ischemia, Na+i accumulation was greater in hearts that eventually developed VF than in hearts that did not develop VF for both band and sham groups (144% versus 128% of control in sham; P < .005) and was the strongest metabolic predictor of VF; ATP depletion was also greater for VF hearts in the sham group. Infusion of the Na(+)-H+ exchange inhibitor 5-(N,N-hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na+i accumulation but similar HEP depletion were observed compared with VF hearts before the onset of VF. Rapid changes in Na+i, pHi, and HEP began with VF, resulting in intracellular Na+i overload (approximately 300% of control) and increased HEP depletion. A delayed postischemic functional recovery occurred in VF hearts, which correlated temporally with the recovery of Na+i. In conclusion, alterations in Na+i were associated with spontaneous VF transitions, consistent with involvement of excess Na+i accumulation in VF initiation and maintenance and with previously reported alterations in Ca2+i with VF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Attenuation of baroreflex changes in cardiac sympathetic efferent activities during acute myocardial ischemia.

Sympathetic efferent activities to the heart during blood pressure changes were investigated in 11 dogs with acute myocardial ischemia. Normalized sympathetic efferent activities recorded in thoracic cardiac nerves decreased or increased as anticipated in response to transient changes in mean arterial pressure (15 to 25 mm Hg with nitroglycerin or phenylephrine, 2 to 8 micrograms/kg, intravenously). A branch of the left circumflex coronary artery was occluded, and the arterial pressure challenges were repeated at 5, 15, and 25 minutes after the occlusion. The control (preocclusion) responses in sympathetic efferent activities to the heart ranged from +/- 2% to 70% (changes relative to steady state normalized at 100%). Reflex sympathetic efferent responses were diminished at 15 and 25 minutes of ischemia. Several sympathetic efferent baroreflex responses during myocardial ischemia were paradoxic. Reflex sympathetic efferent changes were not affected in sham animals. These results indicate that both increases and decreases in cardiac sympathetic efferent activities during baroreflex challenges are attenuated within 15 to 25 minutes of acute coronary artery occlusion. These findings suggest that an abnormal buffering of blood pressure changes during acute myocardial ischemia might lead to autonomic dysfunction that promotes arrhythmogenesis and sudden cardiac death.

Animals↗

PubMed1993

Attenuation of the cardiac effects of cocaine by dizocilpine.

Cocaine abuse causes autonomic and cardiovascular effects that may be life threatening. Attenuation of cocaine-induced seizures has been produced by the noncompetitive antagonist of the N-methyl-D-aspartate receptor channel complex, dizocilpine. The purpose of the present study was, first, to determine effects of dizocilpine on the incidence of pacing-induced ventricular arrhythmias and, second, to evaluate the effects of dizocilpine on cocaine-induced depression of sympathetic efferent activity to the heart. Adult dogs were anesthetized and instrumented for blood pressure and an electrocardiogram. After vagotomy and thoracotomy, electrodes and strain gauges were sutured onto the right atrium and ventricle. A left thoracic sympathetic efferent nerve was isolated and stimulated for analysis of the innervation pattern. Arrhythmias were induced with programmed electrical stimulation of the heart before and during left cardiac sympathetic efferent nerve stimulation. The control incidence of induced arrhythmias was only 2%, which increased to 21% during left sympathetic stimulation. Cocaine (2 mg/kg iv) significantly increased these to 11 and 42%, respectively. Dizocilpine (0.5 mg/kg iv) reduced the incidence of induced ventricular arrhythmias to 2% with cocaine (P < 0.05) and to 19% with cocaine and left sympathetic stimulation (P < 0.01). One or two sympathetic efferent cardiac nerves were stimulated to evaluate innervation patterns. These nerves were severed and prepared for recording multifiber efferent neurograms. Nerve traffic was analyzed by counting positive spikes for 15 s. Control activities were normalized at 100%. Within 6 min, cocaine (2 mg/kg iv) reduced the sympathetic efferent activity to 83 +/- 4% of control (n = 14 nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

A novel acetylcholine receptor-related peptide blocks canine cardiac ganglia and inhibits the nicotinic receptor of PC-12 cells.

A 13 amino acid peptide from the calf muscle acetylcholine receptor has been previously shown to bind both snake neurotoxins and acetylcholine. In the experiments reported here a modified complementary peptide (cAChR) derived from that acetylcholine receptor peptide was tested for biological activity in a canine heart preparation. It was expected that the modified complementary peptide would exhibit either acetylcholine-like effects or acetylcholine inhibiting effects, since, as a complementary peptide to the receptor, it should resemble acetylcholine. In these studies cAChR was administered via the sinus node artery of dog hearts in intact animals which were anesthetized with pentobarbital, intubated, and prepared with local cardiac electrograms and force gauges. cAChR was also injected directly into thoracic sympathetic ganglia. Both approaches demonstrated cAChR inhibition of neural transmission, cAChR was added to the medium of carbachol stimulated PC-12 cells. In these cells, derived from a rat pheochromocytoma, sodium flux is controlled by neural nicotinic receptors. With or without preincubation cAChR inhibited carbachol stimulation of sodium flux, exhibiting a Ki of approximately 9 x 10(-5) (similar to that of hexamethonium). Thus cAChR appears to be a novel synthetic peptide which interrupts nicotinic cholinergic neural transmission by acting as an antagonist of the neural nicotinic receptor.

Amino Acid Sequence↗

PubMed1992

Enhanced induction of ventricular arrhythmias during sympathetic stimulation before and during coronary artery occlusion.

We used programmed electrical stimulation to examine the arrhythmogenic influence of the sympathetic nervous system before and during coronary artery occlusion. In 29 anesthetized dogs the left and/or right stellate ganglia were stimulated at 2-8 hertz. Program-induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia and ventricular fibrillation. Both the number of extrastimuli and the duration of coronary occlusion significantly influenced ventricular arrhythmia induction. After pooling the number of extrastimuli, type of artery occluded, and the duration of occlusion, the influences of unilateral and bilateral stellate stimulations were evaluated. The incidence of induced ventricular arrhythmias was 54% during control conditions (prior to sympathetic stimulation). Right stellate stimulation had no influence on arrhythmogenesis, causing ventricular arrhythmia induction in 52% (NS) of the trials. Left stellate stimulation resulted in increased ventricular arrhythmias (68%; P less than 0.05) in response to programmed electrical stimulation. Bilateral stellate stimulation elevated program-induced ventricular arrhythmias (63%; P less than 0.05). The effects of the stellate stimulations on arrhythmia induction were similar during and up to 180 minutes of coronary occlusion. Thus, the arrhythmogenic influence of sympathetic stimulation was present before and during coronary artery occlusion.

Animals↗

PubMed1992

Cocaine-enhanced arrhythmogenesis: neural and nonneural mechanisms.

Cocaine abuse increases the susceptibility to cardiovascular complications and sudden cardiac death in man. We used programmed electrical stimulation of the heart to examine the arrhythmogenic influence of cocaine. Twenty-three pentobarbital-anesthetized adult dogs underwent programmed electrical stimulation using one to four extrastimuli before and during cocaine infusion. Autonomic decentralization was performed prior to the protocol in eight dogs. Induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia, and ventricular fibrillation. Intravenous cocaine, and subsequent adrenergic and muscarinic receptor blockade, or calcium channel blockade were evaluated for their influence on arrhythmogenesis. The incidence of induced ventricular arrhythmias was significantly elevated following cocaine and was reduced following propranolol and atropine. Verapamil, however, did not reduce the incidence of induced arrhythmias. In addition, cocaine significantly increased arrhythmia induction in decentralized animals, but propranolol, atropine, and phentolamine failed to reduce the proarrhythmic effects of cocaine in these animals. Thus, cocaine has a proarrhythmic effect on the heart with multiple mechanisms. The adrenergic mechanism appears to be a result of neurotransmitter uptake blockade, whereas the likely ionic mechanism is a neurally independent, direct effect on the heart.

Adrenergic beta-Antagonists↗

PubMed1991

Cocaine depresses cardiac sympathetic efferent activity in anesthetized dogs.

Increased use of cocaine has increased the incidence of sudden cardiac death concomitantly, likely due to life-threatening arrhythmias and/or myocardial ischemia. The effects of cocaine on regulation of the heart and circulation by the autonomic nervous system (which is active during arrhythmias and myocardial ischemia) are not fully understood, however. Therefore, we wished to evaluate the influence of intravenous (i.v.) cocaine on spontaneous thoracic cardiac sympathetic efferent nerve activity in anesthetized dogs. In six pentobarbital-anesthetized dogs, blood pressure (BP), heart rate (HR), and two cardiac sympathetic nerves (6 right-sided, 6 left-sided; 3 preganglionic, 9 postganglionic) were simultaneously recorded. Cocaine was infused for 15 min to a total dose of 6 mg/kg. Sympathetic multifiber efferent activities, HR, and BP were recorded continuously throughout the infusion and quantified at 5-min intervals during the infusion and for 45 min after infusion. Neural activities declined sharply to 54.7% of control (p less than 0.01) after only 5 min of infusion. After 15 min of infusion, nerve activity decreased to 39.4% of control (p less than 0.01). Cardiac nerve activity remained depressed (44.9%; p less than 0.01) 45 min after cocaine infusion. Cocaine caused a slight decrease in both HR and BP at 15 min. The rate-pressure product (RPP) decreased significantly during cocaine infusion. Comparable administration of lidocaine (6 mg/kg i.v. in 15 min) failed to influence cardiac sympathetic efferent activities significantly. We conclude that i.v. cocaine significantly depresses spontaneous cardiac sympathetic efferent neural activities in anesthetized dogs.

Animals↗

PubMed1990

A sample computer system for physiological data acquisition and analysis.

This report outlines a sample configuration of a system which records, stores and analyses, graphically and statistically, neurophysiological and cardiovascular recordings during an experiment. The system is composed of sensitive physiological amplifiers, an analog to digital signal conversion board, scientific software, a 80286-based computer with 640 Kb of RAM, and a laser printer. Each component of the system is described along with the specific task(s) it performs.

Analog-Digital Conversion↗

PubMed1990

Differential cardiac sympathetic activity during acute myocardial ischemia.

Efferent sympathetic activities were simultaneously recorded from two thoracic cardiac nerves in 33 chloralose-anesthetized dogs. Efferent innervation patterns were determined by electrical stimulation prior to recording in each animal. One of the nerves selected for recording was shown to innervate the proposed ischemic region, whereas the other nerve was selected because it was shown to innervate nonischemic regions. Left ventricular ischemia was produced by occlusion of a branch of either the left anterior descending (LAD) or left circumflex (LCX) coronary arteries. Heart rate was paced. Cardiac postganglionic sympathetic efferent activities were recorded during a 30-min coronary occlusion in 22 animals. Thirty minutes after LAD occlusion (n = 10), postganglionic sympathetic activity to ischemic myocardium was decreased (84 +/- 5% of control; P less than 0.05) while activity to nonischemic myocardium was unchanged. Thirty minutes after LCX occlusion (n = 12), postganglionic sympathetic activity to ischemic myocardium was also decreased (87 +/- 3% of control; P less than 0.01); however, sympathetic activity to nonischemic myocardium was increased (159 +/- 10% of control; P less than 0.001). Thus, in the anesthetized canine, regional left ventricular ischemia elicits differential sympathetic neural responses that are dependent on the location of the ischemic myocardium as well as the efferent destinations of the nerves. Changes in cardiac postganglionic sympathetic efferent activities are characterized by decreased activity to ischemic regions, with either no change or increased activity to nonischemic regions.

Acute Disease↗

PubMed1990

Effects of deafferentation or sequential occlusions on cardiac sympathetic activity during ischemia.

In 39 anesthetized dogs, we compared the effects of selective afferent sympathectomy, vagotomy, epicardial phenol painting, or a previous coronary occlusion on cardiac sympathetic activities recorded during 30 min of acute myocardial ischemia. Efferent innervation patterns were verified by electrical stimulation, and cardiac efferent activities were simultaneously recorded from two thoracic sympathetic nerves. One nerve was selected for recording because it was shown to innervate the proposed ischemic region, whereas the other nerve was selected because it was shown to innervate nonischemic regions. Left ventricular ischemia was produced by occlusion of a small branch of either the left anterior descending (LAD) or left circumflex (LCX) coronary arteries. Heart rate was paced. Reflex changes in sympathetic activities to ischemic regions were prevented by elimination of afferent fibers with either phenol or bilateral vagotomy. Ablation of sympathetic afferents prevented ischemia-induced reflex changes to nonischemic regions but did not prevent reflex changes to ischemic regions. Reflex changes in cardiac sympathetic activities during a second coronary occlusion of 30 min were vastly different from the initial occlusion but were similar to those observed after local deafferentation. Our findings indicate that 1) differential reflex changes in cardiac sympathetic activities during 30 min of left ventricular ischemia are due to afferent signals originating from the ischemic region, 2) both sympathetic and vagal afferent fibers participate in the ischemia-induced cardio-cardiac reflex, and 3) the nature of the sympathetic reflex response to acute ischemia is influenced by a previous ischemic insult.

Afferent Pathways↗

PubMed1989

On the pathogenesis of angina pectoris and its silence.

Recent interest in silent angina deals in a sense with a double unknown since the pathogenesis of angina pectoris remains unexplained. In this report, we present evidence from two human postmortem studies and from experiments conducted in eleven awake dogs which supports a hypothesis that angina pectoris may be mediated by an intracardiac chemoreceptor receiving its primary blood supply from the proximal coronary circulation. The clinical events and the postmortem findings in both human subjects supported the hypothesis. The somatic responses observed in the awake dogs resembled those of humans with angina pectoris. Because the cardiogenic hypertensive chemoreflex in dogs is maximally elicited by serotonin normally carried by the platelets and released during their aggregation, angina pectoris as well as numerous other clinical events observed during acute myocardial ischemic episodes could be similarly explained as consequences of the activation of a coronary chemoreceptor in man. Thus, at least some and possibly most examples of angina pectoris may be mediated via the coronary chemoreceptor and vagal afferents to the brain, and injury or destruction of this chemoreceptor could interdict the perception of anginal pain.

Adult↗

PubMed1986

Differential inotropic actions of ethmozine and ethacizin (diethylamine analog of ethmozine).

The direct inotropic actions of ethmozine and of its diethylamine analog, ethacizin, were studied in the presence of muscarinic and beta-adrenoreceptor blockade in 12 ferret right ventricular papillary muscles. In each muscle ethmozine caused a small but consistent and significant (p less than 0.05) increase in contractile performance, whereas ethacizin significantly (p less than 0.05) diminished contractility. Although both phenothiazines are fast channel blockers, it appears that the net positive inotropic action of ethmozine is due to its stimulatory effect on the slow inward current and that the negative inotropic action of ethacizin is largely due to its recently demonstrated decreases of the slow inward current.

Adrenergic beta-Antagonists↗

PubMed1986

Differential interaction of adrenergic and cholinergic effects on AV junctional automaticity and AV conduction.

The effects of postsynaptic autonomic interactions on atrioventricular (AV) junctional automaticity and AV conduction were studied in six canine heart in situ using direct injections of norepinephrine (NE) and physostigmine (PSM) into the AV node artery. Injection of NE (0.05 microgram/ml, 2 ml) caused an AV junctional rhythm (AVJR) in every dog. After injection of PSM (10 micrograms/ml, 2 ml), the responses of AVJR to NE were virtually identical to those observed before cholinesterase inhibition (160 +/- 13 vs 162 +/- 12 bpm). In contrast, this moderate cholinesterase inhibition still had a readily demonstrable negative dromotropic effect. In any given dog, depressed AV conduction was characterized by one of two types (I and II) of retrograde atrial capture during AVJR. Before PSM in the AV junction, onset of atrial depolarization during AVJR preceded the onset of ventricular depolarization in both type I and type II responses. After PSM, atrial depolarization occurred later with respect to ventricular depolarization (i.e., during or mostly after ventricular activation) in type I, whereas in the type II responses atrial depolarizations began much earlier than before PSM, thus being completed long before the onset of ventricular activation. Because of such differential responsiveness of AV junctional automaticity and AV conduction and because of the two types of intranodal conduction observed after administration of PSM into the AV junction, we can postulate that under appropriate autonomic imbalance retrograde or antegrade AV block could readily develop in spite of preserved AV junctional automaticity.

Animals↗