Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.
 ...
PMID:Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog. 44 92

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.
 ...
PMID:Differential interaction of adrenergic and cholinergic effects on AV junctional automaticity and AV conduction. 376 77

A 77-year-old man who for 5 months had been being treated with galantamine for early Alzheimer's disease, suddenly became unwell. He was bradycardic and his ECG showed a complete atrioventricular block. This was treated by implantation of a pacemaker. Treatment with galantamine was continued. A month later he had no cardiac symptoms and his dementia score on a cognitive scale had improved. Cholinesterase inhibitors may have adverse effects on the heart. Patients starting treatment with cholinesterase inhibitors should be screened for an increased risk of cardiac arrhythmias by investigating their potassium concentrations and running an ECG.
 ...
PMID:[Complete atrioventricular block during galantamine therapy]. 1722 44

Donepezil is a reversible inhibitor of acetylcholinesterase. Its commonest adverse events are nausea, diarrhoea, malaise, dizziness, and insomnia. Symptomatic cardiac rhythm disturbances associated with the use of donepezil are extremely unusual. An 82 year old patient with Alzheimer's disease (AD) developed complete atrioventricular block and ventricular tachyarrhythmia 1 month after starting treatment with donepezil, and was admitted to the emergency department because of dizziness and syncope. Immediately after admission, a temporary ventricular pacing catheter was placed in the right ventricle. Rhythm was observed to return to a normal sinus rhythm on the fourth day after implantation. Treatment of AD with cholinesterase inhibitors carries a risk of cardiac disturbances. In addition to sinusal bradycardia, it may lead to such major dysrhythmias as complete atrioventricular block and ventricular tachyarrhythmia, as in our case. In this report, we describe symptomatic complete atrioventricular block and ventricular tachyarrhythmia associated with the use of donepezil.
 ...
PMID:Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil. 1685 1

Myasthenia gravis is an autoimmune disorder of the nervous system typically mediated by antibodies against the nicotinic acetylcholine receptor at the neuromuscular junction. Treatment of myasthenia gravis frequently involves the use of cholinesterase inhibitors such as pyridostigmine. Treatment with these agents has been associated with bradycardia and syncope requiring pacemaker implantation. We report a case of a 60-year-old man with a 1-year history of myasthenia gravis treated with pyridostigmine who presented with syncope due to high degree AV block. Before committing the patient to a permanent pacemaker, a trial of medical therapy with hyoscyamine was attempted. Hyoscyamine is a muscarinic antagonist commonly used to block cholinergic side effects associated with pyridostigmine without reducing its efficacy at the neuromuscular junction. Treatment with hyoscyamine resulted in complete resolution of AV block, thereby avoiding pacemaker implantation.
 ...
PMID:Treatment of pyridostigmine-induced AV block with hyoscyamine in a patient with myasthenia gravis. 1771 30

Cu/Zn superoxide dismutase (SOD1) is implicated in various pathological conditions including Down's syndrome, neurodegenerative diseases, and afflictions of the autonomic nervous system (ANS). To assess the SOD1 contribution to ANS dysfunction, especially its influence on cardiac regulation, we studied the heart rate variability (HRV) and cardiac arrhythmias in conscious 12-month-old male and female transgenic mice for the human SOD1 gene (TghSOD1). TghSOD1 mice presented heart rate reduction as compared with control FVB/N individuals. All HRV parameters reflecting parasympathetic activity were increased in TghSOD1. Pharmacological studies confirmed that the parasympathetic tone was exacerbated and the sympathetic pathway was functional in TghSOD1 mice. A high frequency of atrioventricular block and premature ventricular contractions was observed in TghSOD1. By biochemical assays we found that SOD1 activities were multiplied by 9 and 4 respectively in the heart and brainstem of transgenic mice. A twofold decrease in cholinesterase activity was observed in the heart but not in the brainstem. We demonstrate that SOD1 overexpression induces an ANS dysfunction by an exacerbated vagal tone that may be related to impaired cardiac activity of the cholinesterases and may explain the high occurrence of arrhythmias.
 ...
PMID:Increased heart rate variability in mice overexpressing the Cu/Zn superoxide dismutase. 1851 93

Herein we describe 6 cases of patients with Alzheimer's disease presented with syncope, dizziness, and dyspnea soon after the initiation of cholinesterase inhibitor therapy. All patients had bradyarrhythmia on electrocardiogram (ECG). Two patients had complete atrioventricular block, 2 pateints had 2/1 type atrioventricular block, 1 patient had sinus bradycardia and hypersensitive carotid sinus syndrome, and 1 had sick sinus syndrome. All these patients were treated with pacemaker implantation and the cholinesterase inhibitor therapy continued. At 13-month follow-up, no syncope, dizziness, or dyspnea was reported.
 ...
PMID:Anticholinesterase-induced symptoms improved by pacemaker implantation in patients with Alzheimer's disease: analysis of 6 cases. 2281 79