Potential role of K+ currents in the repolarization reserve: the importance of cardiac repolarization reserve in understanding the proarrhythmic side effects of antiarrhythmic drugs

2014 ◽  
Vol 2 (Suppl. 1) ◽  
pp. A1.4
Author(s):  
Norbert Jost
Keyword(s):  
Side Effects ◽  
Antiarrhythmic Drugs ◽  
Potential Role ◽  
Cardiac Repolarization ◽  
Repolarization Reserve ◽  
K Currents

scholarly journals The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations

2021 ◽  
Author(s):  
Leila Topal ◽  
Muhammad Naveed ◽  
Péter Orvos ◽  
Bence Pászti ◽  
János Prorok ◽  
...  
Keyword(s):  
Side Effects ◽  
Action Potentials ◽  
Oral Intake ◽  
Potassium Currents ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Cardiovascular Side Effects ◽  
Channel Inhibition ◽  
Repolarization Reserve ◽  
Electrophysiological Effects

AbstractCannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased IKr, IKs and Ito (only in dog) significantly with corresponding estimated EC50 values of 4.9, 3.1 and 5 µM, respectively, without changing IK1. Although the EC50 value of CBD was found to be higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.

scholarly journals Interaction of different potassium channels in cardiac repolarization in dog ventricular preparations: role of repolarization reserve

2002 ◽  
Vol 137 (3) ◽  
pp. 361-368 ◽  
Author(s):  
Péter Biliczki ◽  
László Virág ◽  
Norbert Iost ◽  
Julius Gy Papp ◽  
András Varró
Keyword(s):  
Potassium Channels ◽  
Cardiac Repolarization ◽  
Repolarization Reserve

Psilocybin-assisted therapy for depression: How do we advance the field?

2019 ◽  
Vol 54 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Sally E Meikle ◽  
Paul Liknaitzky ◽  
Susan L Rossell ◽  
Margaret Ross ◽  
Nigel Strauss ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Potential Role ◽  
Treatment Options ◽  
Clinical Environment ◽  
Psychedelic Drugs ◽  
Key Issues ◽  
New Treatment ◽  
Potential Use

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.

Role of Mg2+ block of the inward rectifier K+ current in cardiac repolarization reserve: A quantitative simulation

2009 ◽  
Vol 47 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Keiko Ishihara ◽  
Nobuaki Sarai ◽  
Keiichi Asakura ◽  
Akinori Noma ◽  
Satoshi Matsuoka
Keyword(s):  
Inward Rectifier ◽  
Cardiac Repolarization ◽  
Repolarization Reserve ◽  
K Current

scholarly journals New progress in understanding the cellular mechanisms of anti-arrhythmic drugs

2018 ◽  
Vol 13 (1) ◽  
pp. 335-339
Author(s):  
Zhe An ◽  
Guang Yang ◽  
Xuanxuan Liu ◽  
Zhongfan Zhang ◽  
Guohui Liu
Keyword(s):  
Atrial Fibrillation ◽  
Ventricular Tachycardia ◽  
Side Effects ◽  
Catheter Ablation ◽  
Antiarrhythmic Drugs ◽  
Ionic Currents ◽  
Cellular Mechanisms ◽  
New Targets

AbstractAntiarrhythmic drugs are widely used, however, their efficacy is moderate and they can have serious side effects. Even if catheter ablation is effective for the treatment of atrial fibrillation and ventricular tachycardia, antiarrhythmic drugs are still important tools for the treatment of arrhythmia. Despite efforts, the development of antiarrhythmic drugs is still slow due to the limited understanding of the role of various ionic currents. This review summarizes the new targets and mechanisms of antiarrhythmic drugs.

scholarly journals Conservative treatment of hypertrophic pyloric stenosis in children

2004 ◽  
Vol 132 (suppl. 1) ◽  
pp. 93-96 ◽  
Author(s):  
Aleksandar Sretenovic ◽  
Zeljko Smoljanic ◽  
Gradimir Korac ◽  
Sanja Sindjic ◽  
Marija Lukac ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Side Effects ◽  
Oral Administration ◽  
Nasogastric Tube ◽  
Potential Role ◽  
Hypertrophic Pyloric Stenosis ◽  
Atropine Sulfate ◽  
Oral Feeding ◽  
Intravenous Atropine

INTRODUCTION. Hypertrophy of the pylorus causing obstruction of the gastric outlet, or infantile hypertrophic pyloric stenosis (IHPS), is the most common indication for abdominal surgery in infancy. The incidence of the condition is 3-4 per 1000 live births, and male infants are affected more often than females, in 4:1 ratio. Vomiting, as the first symptom, most often occurs between the third and fourth week after birth, rarely after second month, but there have been few reports of vomiting as late as 5 months. Etiology of IHPS is still controversial. Two theories have been quoted most: absence of non-adrenergic and non-cholinergic nerve fibers which are mediators of smooth muscle contraction, and absence of nitric oxide inhibitory innervation of pyloric smooth-muscle resulting in unopposed contraction of the sphincter in response to muscarinic stimulation. Atropine sulfate is known to inhibit acetylcholine competitively in neuroreceptors, acting peripherally as a competitive inhibitor of the muscarinic effects of acetylcholine, leading to decreased gastrointestinal peristalsis. This action is believed to be important in IHPS cases. AIM. The aim of this paper is to provide further information on potential role of atropine in the management of patients with IHPS. METHODS. From April 2000 to October 2002, 22 patients (16 boys and 6 girls), aged 21 days to 3 months, with IHPS were treated by oral administration of atropine sulfate in our institution. Diagnosis of IHPS was based on US examination in all cases. A nasogastric tube was inserted and left in situ. Medical treatment involved initial correction of fluid and electrolyte imbalance combined with oral administration of atropine sulfate. Atropin was given in the form of aqueous solution in initial dose of 0.05 mg/kg/d. The total daily dose was divided into 8 equal doses. Each dose was formulated to be given in a volume of 1 ml. Before the administration of each dose of atropine, stomach was decompressed by suction via nasogastric tube. The infant was placed on the right side with the head on the cot elevated 20? to 30? for 15 to 30 minutes after each atropine dose. Oral feeding with 10 ml of 10% glucose was then attempted. If feeding was tolerated, the same dose of atropine was administered 3 hours later, followed by a trial of 20 ml of 10% glucose. If tolerated, 10 ml of conventional formula was then tried after atropine administration 3 hours later. The volume of formula was then increased 10 ml per feed until full feeding (120 ml/kg/d) was tolerated. Dribbling (2-3 times per day) was ignored. If vomiting occurred, the same dose of atropine, volume and type of feed, were tried again 3 hours later, and if still not tolerated, atropine was increased by 1 ?g/kg/dose without increasing the volume of feed. This approach was repeated until oral feeding was tolerated at least twice, and only then the volume of oral feed was increased. During night shift (between 11 p.m. and 5 a.m.), atropine concentration and amount of oral feed were not increased. If vomiting recurred, the volume of oral feed was decreased to the last tolerated volume and maintained until the following day. Oral atropine was increased until predetermined maximum oral dose (0.1 mg/kg/d) was reached. If oral administration of atropine was ineffective, a decision to perform pyloromyotomy was made no later than 7 days after commencement of oral atropine. RESULTS. Atropine had effect (vomiting frequency less than twice per day) on average 3.29 days (range 1-7 days) from commencement. Oral atropine was tolerated very well, and was effective in 18 cases. Four cases were referred to pyloromyotomy, on day 4 (2 patients), day 5 (1 patient) and on day 6 (1 patient) of atropine treatment. Therapy was continued until US showed normalization of pyloric muscle thickness, passage of food through wide pyloric channel and until patients started gaining weight. Average duration of therapy was 24.05 days (11-39 days). Neither of patients from our group was treated with intravenous atropine sulfate. DISCUSSION. Although intravenous atropine is more effective (as shown by Nagita et al [7]), there is an increased incidence of side effects such as flushing and tachycardia. Oral atropine has been used successfully by other teams without side effects [9, 11, 13], and there were no side effects or complications related to the use of atropine in this study. Prospective, randomized study comparing outcomes of medical versus surgical management of IHPS in our hospital has been currently in progress and will provide further information on potential role of atropine in the management of patients with IHPS. CONCLUSION. We believe it is unlikely that oral or intravenous atropine will ever replace surgery for IHPS, but it may be a good alternative to pyloromyotomy, particularly in children with major concurrent primary disease, or when parents are not enthusiastic about surgery in so young children.

Migraine

1994 ◽  
Vol 15 (11) ◽  
pp. 456-456
Keyword(s):  
Side Effects ◽  
Potential Role ◽  
Reye Syndrome ◽  
Analgesic Medication ◽  
Effective Prophylaxis ◽  
Low Dosage

A reader raised two questions regarding the article on migraine in children (Pediatrics in Review. 1994; 15:94-101): 1. Is low dosage aspirin effective prophylaxis for migraine? 2. What is the role of platelets in the pathogenesis of migraine? Dr. Singer responds: Aspirin does, indeed, provide relief for many of those who have migraines. Its overuse, however, can have serious side effects. Further, some are hesitant to use it based on established reports of headaches induced by chronic aspirin treatment and its potential role as a factor in Reye syndrome. Although the value of aspirin in headache syndromes may be related, in part, to its effect on platelets, it also is a well-established analgesic medication.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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