piperidines and Tachycardia--Ventricular

piperidines has been researched along with Tachycardia--Ventricular* in 28 studies

Reviews

3 review(s) available for piperidines and Tachycardia--Ventricular

ArticleYear
Bruton's tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation.
    Current oncology reports, 2021, 08-03, Volume: 23, Issue:10

    The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton's Tyrosine Kinase inhibitors (BTKIs).. Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

    Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Atrial Fibrillation; Cardiotoxicity; Heart Failure; Hemorrhage; Humans; Hypertension; Piperidines; Protein Kinase Inhibitors; Tachycardia, Ventricular

2021
    The Lancet. Microbe, 2020, Volume: 1, Issue:1

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus-host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown.. We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's. As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV.. May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.. Lower levels of total T3 were strongly correlated with in-hospital mortality in patients with SCMP. A low T3 level might suggest poor prognosis in patients with SCMP.

    Topics: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Bacterial; Anxiety Disorders; Arecaceae; Arrhythmias, Cardiac; Autonomic Nervous System; Bacterial Proteins; Behavior Therapy; Burkholderia pseudomallei; Caco-2 Cells; Campylobacter; Campylobacter Infections; Carbazoles; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Chickens; Computer Simulation; Coumarins; COVID-19; Cross-Sectional Studies; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Diabetes Mellitus, Type 1; Diarrhea; Dietary Supplements; Echocardiography; Educational Measurement; Electrocardiography, Ambulatory; Endoribonucleases; Exercise; Exercise Therapy; Faculty, Dental; Farms; Fear; Female; Flame Retardants; Florida; Gene Expression Regulation, Plant; Halogenated Diphenyl Ethers; Hearing Loss, Sudden; Heart Rate; HIV Infections; Hospital Mortality; Humans; Hypertension; Hypoglycemia; Immunity; In Situ Hybridization; Japan; Kinetics; Kuwait; Lung Neoplasms; Macaca mulatta; Macrophages; Male; Masked Hypertension; Melioidosis; Methyltransferases; Mice; Mice, Inbred BALB C; Middle Aged; Molecular Docking Simulation; Molecular Dynamics Simulation; Myocardium; Oryza; Patient Education as Topic; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Piperidines; Plant Extracts; Plant Proteins; Platelet Count; Poultry Diseases; Prevalence; Protease Inhibitors; Protein Kinase Inhibitors; Protein Kinases; Rabbits; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Resistance Training; Retrospective Studies; Risk Factors; SARS-CoV-2; Saudi Arabia; Severe acute respiratory syndrome-related coronavirus; Students; Substance-Related Disorders; Surveys and Questionnaires; Swine; Tachycardia, Ventricular; Takotsubo Cardiomyopathy; Thyroid Gland; Transcriptome; Transfection; Tropism; United Arab Emirates; Virulence; Virulence Factors; Writing

2020
Drug-induced cardiac arrhythmias: incidence, prevention and management.
    Drug safety, 1997, Volume: 17, Issue:4

    Drugs can cause cardiac arrhythmias in a number of clinical situations, and many of the implicated agents are used to treat non-cardiac conditions. These adverse effects are frequently idiosyncratic, but are often mediated via triggered activity causing torsade de pointes. Drugs being used for treatment of cardiac conditions may promote arrhythmias by re-entrant mechanisms or via triggered activity. Many drugs may cause cardiac arrhythmic complications when taken in excessive amounts. Keys to reducing the incidence of drug-induced cardiac arrhythmias include increased awareness among the medical, pharmaceutical and nursing professions of the potential problems in using certain agents, especially in specific situations. Appropriate monitoring when such treatment is essential and, after diagnosis, prompt withdrawal of the offending agent and treatment for the arrhythmia should be initiated.

    Topics: Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anti-Infective Agents; Arrhythmias, Cardiac; Bradycardia; Cisapride; Digitalis Glycosides; Electrocardiography; Gastrointestinal Agents; Histamine H1 Antagonists; Humans; Incidence; Piperidines; Sotalol; Tachycardia, Ventricular; Torsades de Pointes

1997

Trials

1 trial(s) available for piperidines and Tachycardia--Ventricular

ArticleYear
A Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of JDTic.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015, Volume: 40, Issue:9

    Animal studies suggest that kappa opioid receptor antagonists (KORAn) potentially could treat a wide variety of addictive and depressive disorders. We assessed the KORAn JDTic for safety, tolerability, and pharmacokinetics in a double-blind, placebo-controlled, randomized trial evaluating single oral doses in healthy adult males. Predose and postdose safety assessments included orthostatic vital signs; 6-lead continuous telemetry monitoring (approximately 16 h predose to 24 h postdose); 12-lead electrocardiograms (ECGs); clinical chemistry, hematology, coagulation, and urinalysis; psychomotor functioning (using the Wayne Saccadic Fixator (WSF)); and adverse events. As a potential indicator of JDTic effects on affect, the POMS Standard instrument was administered predose and daily postdose Days 1-6. At 1 mg, 2 of the 6 JDTic (and 0/6 placebo) subjects experienced a single, asymptomatic event of multiple beats of nonsustained ventricular tachycardia (NSVT). Their events were temporally similar with respect to time postdose (and the postdose timing of an NSVT event in a monkey). These events triggered a study stopping rule. No differences were observed between the placebo and JDTic subjects with respect to clinical chemistry, hematology, coagulation, urinalysis, orthostatic vital signs, WSF, or 12-lead ECG parameters. Plasma JDTic levels were below the lower limit of quantitation (0.1 nM) in all subjects. There were no significant differences in POMS scores between the placebo and JDTic groups. Although the evidence is circumstantial, it suggests that NSVT is a potential JDTic toxicity in humans. Given the therapeutic potential of KORAn, further investigation is needed to determine whether a significant JDTic human cardiac effect indeed exists, and if so, whether it is specific to JDTic or represents a KORAn class effect.

    Topics: Administration, Oral; Adolescent; Adult; Area Under Curve; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Fasting; Humans; Male; Middle Aged; Piperidines; Receptors, Opioid, kappa; Tachycardia, Ventricular; Tetrahydroisoquinolines; Time Factors; Young Adult

2015

Other Studies

24 other study(ies) available for piperidines and Tachycardia--Ventricular

ArticleYear
Ventricular Tachycardia Caused by Ibrutinib.
    The Journal of emergency medicine, 2017, Volume: 53, Issue:2

    Topics: Adenine; Electrocardiography; Humans; Piperidines; Pyrazoles; Pyrimidines; Tachycardia; Tachycardia, Ventricular

2017
A Perfect Storm: Tyrosine Kinase Inhibitor-Associated Polymorphic Ventricular Tachycardia.
    The Journal of emergency medicine, 2017, Volume: 52, Issue:4

    Oral tyrosine kinase inhibitors (TKIs) are becoming increasingly common in oncology practice due to ease of administration and patient preference. This class of medications is relatively unknown to emergency physicians.. Here we present a case of electrical storm (ES) thought to be associated with ibrutinib, a TKI. The ES was unabated despite antidysrhythmic therapy and electrical cardioversion, and was treated with supportive care, which eventually included the use of extracorporeal membrane oxygenation. This patient had no risk factors or apparent causes of recurrent ventricular tachycardia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ES has not previously been described with ibrutinib, but may be associated with off-target effects of the drug.

    Topics: Adenine; Amiodarone; Anti-Arrhythmia Agents; Antineoplastic Agents; Cardiotonic Agents; Electric Countershock; Electrocardiography; Electrophysiology; Emergency Service, Hospital; Extracorporeal Membrane Oxygenation; Humans; Intensive Care Units; Intra-Aortic Balloon Pumping; Isoproterenol; Lidocaine; Magnesium; Male; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Respiration, Artificial; Syncope; Tachycardia, Ventricular; Torsades de Pointes; Waldenstrom Macroglobulinemia; Workforce

2017
Ibrutinib, an Approved Tyrosine Kinase Inhibitor as a Potential Cause of Recurrent Polymorphic Ventricular Tachycardia.
    JACC. Clinical electrophysiology, 2016, Volume: 2, Issue:7

    Topics: Adenine; Aged; Electrocardiography; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Tachycardia, Ventricular

2016
Alogliptin, a dipeptidyl peptidase-4 inhibitor, regulates the atrial arrhythmogenic substrate in rabbits.
    Heart rhythm, 2015, Volume: 12, Issue:6

    Dipeptidyl peptidase-4 (DPP-4) inhibitors were recently reported to have cardioprotective effects via amelioration of ventricular function. However, the role of DPP-4 inhibition in atrial remodeling, especially of the arrhythmogenic substrate, remains unclear.. We investigated the effects of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) in a rabbit model of heart failure caused by ventricular tachypacing (VTP).. Rabbits subjected to VTP at 380 bpm for 1 or 3 weeks, with or without alogliptin treatment, were assessed using echocardiography, electrophysiology, histology, and immunoblotting and compared with nonpaced animals.. VTP rabbits exhibited increased duration of atrial burst pacing-induced AF, whereas administration of alogliptin shortened this duration by 73%. The extent of atrial fibrosis after VTP was reduced by 39% in the alogliptin-treated group. VTP rabbits treated with alogliptin displayed a 1.6-fold increase in left atrial myocardial capillary density compared with nontreated rabbits. A 2-fold increase in endothelial nitric oxide synthase (eNOS) phosphorylation was observed in the left atrium of alogliptin-treated rabbits compared with nontreated rabbits. Moreover, a nitric oxide synthase inhibitor (N(ω)-nitro-l-arginine methyl ester) blocked the beneficial effects of alogliptin on AF duration, fibrosis, and capillary density.. Alogliptin shortened the duration of AF caused by VTP-induced fibrotic atrial tissue by augmenting atrial angiogenesis and activating eNOS. Our findings suggest that DPP-4 inhibitors may be useful in the prevention of heart failure-induced AF.

    Topics: Animals; Atrial Fibrillation; Blotting, Western; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Echocardiography; Electrophysiology; Endothelium; Enzyme-Linked Immunosorbent Assay; Fibrosis; Fluorescent Antibody Technique; Heart Atria; Heart Failure; Male; Neovascularization, Physiologic; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Phosphorylation; Piperidines; Rabbits; Tachycardia, Ventricular; Uracil

2015
Kappa Antagonist JDTic in Phase 1 Clinical Trial.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015, Volume: 40, Issue:9

    Topics: Humans; Male; Piperidines; Receptors, Opioid, kappa; Tachycardia, Ventricular; Tetrahydroisoquinolines

2015
Remifentanil-midazolam sedation provides hemodynamic stability and comfort during epicardial ablation of ventricular tachycardia.
    Journal of cardiovascular electrophysiology, 2011, Volume: 22, Issue:4

    Epicardial ablation of ventricular tachycardia (VT) presents multiple challenges for anesthetic management. General anesthesia lowers blood pressure, may interfere with arrhythmia mapping, and use of muscle relaxants precludes identification of the phrenic nerve. We describe a case in which remifentanil with minimal doses of midazolam was employed in a series of epicardial VT ablations and noninvasive programmed stimulations (NIPS), including 5 external cardioversions and discuss the advantages of this approach.

    Topics: Catheter Ablation; Drug Therapy, Combination; Hemodynamics; Humans; Hypnotics and Sedatives; Male; Midazolam; Piperidines; Remifentanil; Tachycardia, Ventricular; Treatment Outcome; Young Adult

2011
Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog.
    Pacing and clinical electrophysiology : PACE, 2010, Volume: 33, Issue:8

    Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I(Kr) blocker, E-4031, each administered to five open-chest dogs.. We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation-recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid-myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation.. Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E-4031, bepridil caused mild, reverse use-dependent changes in ventricular repolarization, and less ARI dispersion than E-4031 during slow ventricular pacing. Both drugs increased ARI(max) and cycle length at 50% of ARI(max), though the changes were smaller after bepridil than after E-4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E-4031 versus no dog treated with bepridil.. Unlike the pure I(kr) blocker, E-4031, bepridil exhibited weak properties of reverse use-dependency and protected against sympathetic stimulation-induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator.

    Topics: Animals; Anti-Arrhythmia Agents; Bepridil; Blood Pressure; Calcium Channel Blockers; Cerebral Revascularization; Dogs; Electrophysiologic Techniques, Cardiac; Heart Rate; Piperidines; Pyridines; Tachycardia, Ventricular; Ventricular Function, Left

2010
Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na(+) current in the heart.
    American journal of physiology. Heart and circulatory physiology, 2009, Volume: 297, Issue:3

    Reduction of repolarization reserve increases the risk of arrhythmia. We hypothesized that inhibition of K(+) current (I(K)) to decrease repolarization reserve would unmask the proarrhythmic role of endogenous, physiological late Na(+) current (late I(Na)). Monophasic action potentials (MAP) and 12-lead electrocardiogram were recorded from female rabbit isolated hearts. To block I(K) and reduce repolarization reserve, E-4031, 4-aminopyridine, and BaCl(2) were used; to block endogenous late I(Na), tetrodotoxin (TTX) and ranolazine were used. E-4031 (1-60 nM) concentration-dependently prolonged MAP duration (MAPD(90)) and increased duration of the T wave from T(peak) to T(end) (T(peak)-T(end)), transmural dispersion of repolarization (TDR), and beat-to-beat variability (BVR) of MAPD(90). E-4031 caused spontaneous and pause-triggered polymorphic ventricular tachycardia [torsade de pointes (TdP)]. In the presence of 60 nM E-4031, TTX (0.6-3 muM) and ranolazine (5-10 muM) shortened MAPD(90), decreased TDR, BVR, and T(peak)-T(end) (n = 9-20, P < 0.01), and abolished episodes of TdP. In hearts treated with BaCl(2) or 4-aminopyridine plus E-4031, TTX (0.6-3 muM) shortened MAPD(90) and decreased T(peak)-T(end). Ranolazine could not reverse the effect of E-4031 to inhibit human ether-a-go-go-related gene (HERG) K(+) current; thus, the reversal by ranolazine of effects of E-4031 was likely due to inhibition of late I(Na) and not to antagonism of the HERG-blocking action of E-4031. We conclude that endogenous, physiological late I(Na) contributes to arrhythmogenesis in hearts with reduced repolarization reserve. Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by I(K) inhibitors.

    Topics: 4-Aminopyridine; Acetanilides; Action Potentials; Animals; Anti-Arrhythmia Agents; Barium Compounds; Cell Line; Chlorides; Enzyme Inhibitors; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Female; Heart Conduction System; Humans; Kidney; Patch-Clamp Techniques; Piperazines; Piperidines; Potassium Channel Blockers; Pyridines; Rabbits; Ranolazine; Sodium; Sodium Channel Blockers; Sodium Channels; Tachycardia, Ventricular; Tetrodotoxin; Torsades de Pointes

2009
Glibenclamide attenuates the antiarrhythmic effect of endotoxin with a mechanism not involving K(ATP) channels.
    Vascular pharmacology, 2007, Volume: 46, Issue:2

    The role of K(ATP) channels in the antiarrhythmic effect of Escherichia coli endotoxin-induced nitric oxide synthase (iNOS) was examined in an anesthetised rat model of myocardial ischemia and reperfusion arrhythmia by using glibenclamide (1 mg kg(-1)), nateglinide (10 mg kg(-1)) and repaglinide (0.5 mg kg(-1)). Endotoxin (1 mg kg(-1)) was administered intraperitoneally 4 h before the occlusion of the left coronary artery and glibenclamide, nateglinide or repaglinide was administered 30 min before coronary artery occlusion. We also evaluated the effects of K(ATP) channel blockers and nonselective K(+) channel blocker tetraethylammonium (TEA) on cardiac action potential configuration in the atria obtained from endotoxemic rats. The mean arterial blood pressure of rats receiving endotoxin was lower during both the occlusion and reperfusion periods. Endotoxin significantly reduced the total number of ectopic beats and the duration of ventricular tachycardia. Glibenclamide, but not nateglinide and repaglinide, prevented the hypotension and antiarrhythmic effects of endotoxin. Atria obtained from endotoxin-treated rats had prolonged action potential duration. This effect was abolished with pretreatment of iNOS inhibitors, l-canavanine and dexamethasone and perfusion of glibenclamide, but not with TEA and non-sulfonylurea drug, nateglinide. We demonstrated that glibenclamide inhibits the antiarrhythmic effect of endotoxin and this effect does not appear to involve K(ATP) channels.

    Topics: Action Potentials; Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Blood Pressure; Carbamates; Cyclohexanes; Disease Models, Animal; Drug Interactions; Endotoxemia; Glyburide; Heart Atria; Heart Conduction System; Lipopolysaccharides; Male; Myocardial Ischemia; Nateglinide; Phenylalanine; Piperidines; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Tetraethylammonium; Time Factors; Ventricular Fibrillation; Ventricular Premature Complexes

2007
Calculate the QT interval in patients taking drugs for dementia.
    BMJ (Clinical research ed.), 2007, Sep-15, Volume: 335, Issue:7619

    Topics: Aged; Dementia; Donepezil; Female; Humans; Indans; Long QT Syndrome; Nootropic Agents; Piperidines; Tachycardia, Ventricular

2007
Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil.
    Emergency medicine journal : EMJ, 2006, Volume: 23, Issue:8

    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.

    Topics: Aged, 80 and over; Alzheimer Disease; Cardiac Pacing, Artificial; Cholinesterase Inhibitors; Donepezil; Electrocardiography; Heart Block; Humans; Indans; Male; Piperidines; Tachycardia, Ventricular; Treatment Outcome

2006
Restitution properties and occurrence of ventricular arrhythmia in LQT2 type of long QT syndrome.
    Journal of cardiovascular electrophysiology, 2002, Volume: 13, Issue:9

    The aim of this study was to clarify the ventricular tachyarrhythmia mechanism induced by the I(Kr)-blocking agent E4031, simulating the LQT2 form. Electrophysiologic properties were examined in 13 canines before and after administration of E4031.. Thirty-six needle electrodes were inserted into the anterior left ventricular wall. From each needle, local unipolar electrograms were obtained from four intramural sites. Activation time (AT) and activation-recovery interval (ARI) were measured. To evaluate the susceptibility to ventricular arrhythmia, intramural ARI dispersions and the restitution relationship between ARI and diastolic interval were calculated. After E4031 administration, ARI prolonged uniformly in each myocardial layer. However, ARI dispersion was not augmented compared with control. The slope of the ARI restitution curve after E4031 was significantly steeper than control. A steep slope may result from augmented ARI alternans. In 11 of the 13 canines, ventricular tachyarrhythmia was induced by programmed stimulation after E4031, whereas no arrhythmia was induced by the same protocol in control.. Steepness of electrical restitution may play a major role in arrhythmogenicity in LQT2 hearts.

    Topics: Animals; Anti-Arrhythmia Agents; Cardiac Pacing, Artificial; Disease Models, Animal; Disease Susceptibility; Dogs; Electrocardiography; Electrophysiologic Techniques, Cardiac; Heart Conduction System; Heart Ventricles; Long QT Syndrome; Models, Cardiovascular; Piperidines; Pyridines; Tachycardia, Ventricular

2002
4-aminopyridine inhibits the occurrence of ventricular fibrillation but not ventricular tachycardia in the reperfused, P6olated rat heart.
    Japanese circulation journal, 2000, Volume: 64, Issue:8

    The 4-aminopyridine (4-AP)-sensitive transient outward current (Ito) has been reported to play an important role in the ischemia- or high [Ca2+]o-induced reentrant ventricular arrhythmias. However, the role of 4-AP sensitive Ito in reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode solution (control), and treated with 0.5 micromol/L verapamil, 1 micromol/L glibenclamide, 10 micromol/L E-4031 or 2 mmol/L 4-AP. After a 10-min perfusion, hearts were subjected to 30-min global ischemia followed by 10-min reperfusion. The effects of the ion-channel blockers on the incidence of ventricular tachycardia (VT), torsades de pointes (Tdp) and ventricular fibrillation (VF) during the reperfusion period were investigated. Verapamil and 4-AP abolished VF and Tdp. The incidence of VT was also attenuated by verapamil, but not by 4-AP. Glibenclamide and E-4031 (a blocker of a rapidly activating component of delayed rectifier K+ current) did not affect the incidence of those tachyarrhythmias. Accordingly, (1) the underlying mechanism of VF or Tdp is different from that of VT, and (2) 4-AP sensitive Ito is required for the occurrence of reperfusion Tdp or VF in the present model.

    Topics: 4-Aminopyridine; Animals; Anti-Arrhythmia Agents; Blood Flow Velocity; Glyburide; Heart; Heart Rate; In Vitro Techniques; Male; Myocardial Reperfusion; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Torsades de Pointes; Ventricular Fibrillation; Verapamil

2000
Metabolism of MK-499, a class III antiarrhythmic agent, in rats and dogs.
    Drug metabolism and disposition: the biological fate of chemicals, 1998, Volume: 26, Issue:5

    MK-499 [(+)-N-[1'-(6-cyano-1, 2, 3, 4-tetrahydro-2(R)-naphthalenyl)-3, 4-dihydro-4(R)-hydroxyspiro(2H-1-benzopyran-2, 4'-piperidin)-6-yl]methanesulfonamide] monohydrochloride is an investigational class III antiarrhythmic agent for treatment of malignant ventricular tachyarrhythmias. The disposition of [3H]MK-499 and [14C]MK-499 was studied in rats and dogs after oral and iv administration. MK-499 was concentrated in organs of excretion and the heart. In the rat, urinary radioactivity elimination values after iv (0.5 mg/kg) and oral (6.25 mg/kg) doses were 21 +/- 3% and 10 +/- 2%, respectively. Corresponding fecal recoveries were 68 +/- 6% and 78 +/- 7%. Similar results were found after corresponding doses of [14C]MK-499. In dogs, urine and feces accounted for 16 +/- 3% and 75 +/- 4% of recovered radioactivity after a [3H]MK-499 iv dose (0.1 mg/kg). Corresponding recoveries after an oral dose (1 mg/kg) were 12 +/- 2% and 76 +/- 3%. Biliary (0-24 hr) excretion accounted for 39 +/- 5% and 41 +/- 18% of [3H] and [14C] oral doses in rats, respectively. Dogs excreted 34% of [3H] oral dose in (0-24 hr) bile. The data indicated that a substantial amount of MK-499 was absorbed by rats and dogs. MK-499, metabolite I (formed by loss of N-substitution), and metabolite II (an acid formed by metabolic scission across the benzopyran ring) each represented 30% of rat urinary label. Rat bile contained MK-499 (10%), II (20%), and IV (10%), which was formed by carbon-4 hydroxylation of the tetralin ring. Additionally, rat bile included glutathione (V) and N-acetyl-1-cysteine (VI) conjugates of a ring-opened metabolite. Metabolite III, a positional isomer of IV, was excreted in rat urine. The major labeled species excreted in dog bile were unchanged MK-499 and its glucuronide (VII), which, respectively, represented 50% and 30% of the biliary radioactivity. MK-499 and a small amount of I represented dog urinary radioactivity. The bioavailability of MK-499 was high in dogs (100%) but low in rats (17%). This difference was probably due to the more extensive presystemic metabolism of MK-499 in rats.

    Topics: Animals; Anti-Arrhythmia Agents; Benzopyrans; Biological Availability; Chromatography, High Pressure Liquid; Dogs; Dose-Response Relationship, Drug; Magnetic Resonance Spectroscopy; Male; Metabolic Clearance Rate; Piperidines; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Tissue Distribution

1998
Effects of class I and III antiarrhythmic drugs on ventricular tachycardia-interrupting critical paced cycle length with rapid pacing.
    Japanese circulation journal, 1998, Volume: 62, Issue:4

    The most common mechanism of sustained ventricular tachycardia (VT) is re-entry with an excitable gap, but the electrophysiologic properties and response to antiarrhythmic drugs in the area of slow conduction are not yet fully known. The purpose of this study was to assess the effects of a class I antiarrhythmic drug (procainamide) and class III agents (amiodarone, E-4031, and MS-551) on re-entrant VT using the width of the zone of entrainment. The cycle length (CL) of VT (VTCL), the block CL that was the longest paced CL that interrupted the VT, and the width of the zone of entrainment, defined as the difference between VTCL and block CL, were compared before and after treatment with antiarrhythmic drugs. The VTCL was prolonged significantly from 308+/-63 to 410+/-77 msec after procainamide (p<0.005) but was not changed after the administration of the class III agents: from 294+/-50 to 292+/-13 msec after amiodarone, and from 305+/-47 to 313+/-31 msec after E-4031 or MS-551 (p=NS). The block CL was prolonged from 255+/-61 to 331+/-70 msec after procainamide (p <0.01), from 256+/-20 to 260+/-25 msec after amiodarone, and unchanged after E-4031 or MS-551 (253+/-31 msec before and 270+/-43 msec after) (p=NS). The width of the zone of entrainment as a representative of the width of the excitable gap was changed from 52+/-26 to 79+/-35 msec (p<0.05) after procainamide, whereas it was unchanged after amiodarone (48+/-7 msec before and 43+/-7 msec after) and after E-4031 or MS-551 (50+/-10 msec before and 40+/-9 msec after). Therefore, amiodarone, E-4031, and MS-551 did not affect VTCL and block CL whereas procainamide increased these parameters. The excitable gap substituting as the zone of entrainment was increased by procainamide but slightly reduced by amiodarone, E-4031, and MS-551. The effects of these antiarrhythmic drugs on the excitable gap of re-entrant VT were variable and should be examined further.

    Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Child; Electrophysiology; Female; Heart Conduction System; Humans; Male; Middle Aged; Piperidines; Pyridines; Pyrimidinones; Tachycardia, Ventricular

1998
Comparison of electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, in patients with ventricular tachyarrhythmias.
    Japanese heart journal, 1998, Volume: 39, Issue:4

    Electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, were evaluated in 5 and 6 patient with ventricular tachyarrhythmia, respectively. Six patients had sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation (VF). Electrophysiologic study was performed before and after administration of E-4031 and MS-551 [E-4031; loading infusion 9 micrograms/kg for 5 min + 0.15 microgram/kg/min, MS-551; loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min]. The QT intervals were significantly prolonged after administration of E-4031 and MS-551 from 409 +/- 37 to 455 +/- 49 msec (11%), and from 359 +/- 52 to 411 +/- 63 msec (14%), respectively. The QTc intervals were significantly prolonged from 457 +/- 17 to 494 +/- 24 msec (8%), and from 410 +/- 36 to 452 +/- 47 (10%), respectively. There were no significant differences in the QT and QTc intervals between these two agents. The right ventricular effective refractory period (VERP) with E-4031 was prolonged at 600 (from 244 +/- 27 to 270 +/- 31 msec, 11 +/- 2%), 400 (from 222 +/- 23 to 242 +/- 24 msec, 9 +/- 3%), and 300 msec (from 206 +/- 19 to 218 +/- 25 msec, 6 +/- 4%), and those with MS-551 were prolonged at 600 (from 240 +/- 23 to 268 +/- 23 msec, 12 +/- 2%), 400 (from 225 +/- 22 to 250 +/- 24 msec, 11 +/- 4%), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, 7 +/- 4%). Both E-4031 and MS-551 prolonged VERP in a "reverse" use-dependent manner without changing the conduction velocity. E-4031 prevented the induction of VT in one patient. MS-551 prevented the induction of VT and VF in one patient each. Further evaluation of these selective class III agents may be needed to determine if higher doses are required to achieve the pharmacological effects in patients with ventricular tachyarrhythmias.

    Topics: Adult; Aged; Anti-Arrhythmia Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Female; Heart Ventricles; Humans; Infusions, Intravenous; Male; Middle Aged; Piperidines; Pyridines; Pyrimidinones; Tachycardia, Ventricular; Treatment Outcome

1998
Cisapride, erythromycin and arrhythmia.
    Anaesthesia and intensive care, 1996, Volume: 24, Issue:6

    Topics: Adult; Anti-Bacterial Agents; Cisapride; Drug Interactions; Erythromycin; Humans; Male; Piperidines; Tachycardia, Ventricular

1996
Antiarrhythmic action of the new calcium antagonist [1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine dihydrochloride.
    Arzneimittel-Forschung, 1996, Volume: 46, Issue:12

    Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine in rats, and by ouabain in guinea-pigs were used as experimental models for studying the effects of a new calcium antagonist AR-1 ([1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine, calcium channel blocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation caused 90% lethality (ventricular fibrillation) with 12.5 min in untreated control cats, which was prevented by administration of AR-1 (4 mg/kg body weight (b.w.) before or after arrhythmia induction. Pretreatment with AR-1 afforded protection in a dose-related fashion. A dose of 1.5 mg/KG b.w. increased survival to 45%, and all cats dosed with 3 to 5 mg/Kg b.w. survived. CaCl2 (180 mg/Kg b.w., i.v.) induced ventricular fibrillation and 100% lethality. These effects were completely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w.). Epinephrine-induced ventricular arrhythmias were also prevented by the same dose of AR-1. AR-1 (5 mg/kg b.w.) did not prevent ouabain (0.5 mg/kg b.w.)-induced arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective effects during 67 +/- 7.7 min. The results from these animal studies, in conjunction with previously studies demonstrating coronarodilatory and anti-platelet efficacy of this compound, collectively suggest that AR-1 has a potential to become a useful antianginal and antiarrhythmic therapeutic agent.

    Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Calcium Chloride; Cardiovascular Agents; Coronary Vessels; Electrocardiography; Epinephrine; Male; Ouabain; Piperidines; Rats; Rats, Wistar; Tachycardia, Ventricular; Ventricular Fibrillation

1996
Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide.
    Heart and vessels, 1995, Volume: 10, Issue:1

    We investigated the antiarrhythmic effects of bidisomide (SC-40230), a new class I antiarrhythmic drug, in early-phase ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. The effects of bidisomide were compared with those of mexiletine (MXT) and disopyramide (DSP), established class I antiarrhythmic drugs. Drugs were administered intravenously, 5 min before induction of coronary occlusion. Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion. In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5-min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP. All three drugs significantly slowed the heart rate. Our results suggest that bidisomide may effectively reduce the severity of life-threatening ventricular arrhythmias that occur during acute coronary syndrome.

    Topics: Animals; Anti-Arrhythmia Agents; Blood Pressure; Cardiac Complexes, Premature; Coronary Disease; Disopyramide; Heart Rate; Male; Mexiletine; Myocardial Reperfusion Injury; Piperidines; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Ventricular Fibrillation

1995
Protection against programmed electrical stimulation-induced ventricular tachycardia and sudden cardiac death by NE-10064, a class III antiarrhythmic drug.
    Journal of cardiovascular pharmacology, 1993, Volume: 22, Issue:6

    The electrophysiologic and antifibrillatory properties of NE-10064 were studied in vivo in a conscious canine model of sudden cardiac death. Purpose bred male mongrel dogs weighing 14.5-21.5 kg were anesthetized, and surgical anterior myocardial infarction (MI) was induced by a 2-h occlusion, with reperfusion, of the left anterior descending coronary artery (LAD). Three to 5 days after induction of anterior wall MI, animals were subjected to testing by programmed electrical stimulation (PES). As compared with predrug incidence (12 of 12), NE-10064 (10 mg/kg intravenously, i.v.) reduced (p < 0.05) the incidence (8 of 12) of PES-induced ventricular tachycardia (VT). All but 1 control animal remained inducible after vehicle (5% dextrose in water). The cycle length of induced VT was not prolonged by NE-10064 (0.245 +/- 0.046 s predrug vs. 0.301 +/- 0.060 s postdrug). NE-10064 increased ventricular effective refractory period (VERP 166 +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p = 0.045). The drug did not affect ECG-indexes of conduction velocity: QRS and P-R intervals were not affected, nor were activation delay and conduction time of noninfarcted and infarcted myocardium. In the sudden cardiac death protocol, NE-10064 protected (p = 0.018) against ischemia-induced ventricular fibrillation (VF, 75% survival with drug vs. 25% survival without drug). NE-10064 afforded protection (p = 0.040) throughout 14 h posterolateral ischemia in the presence of the previous anterior infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Anti-Arrhythmia Agents; Death, Sudden, Cardiac; Disease Models, Animal; Dogs; Electric Stimulation; Electrocardiography; Electrophysiology; Heart Rate; Hydantoins; Imidazoles; Imidazolidines; Male; Myocardial Infarction; Piperazines; Piperidines; Tachycardia, Ventricular; Ventricular Fibrillation

1993
Effect of E-4031, a new class III antiarrhythmic drug, on reentrant ventricular arrhythmias: comparison with conventional class I drugs.
    Cardiovascular drugs and therapy, 1993, Volume: 7 Suppl 3

    We evaluated the antiarrhythmic efficacy of E-4031, a new class III drug, and compared it with that of conventional class I and II antiarrhythmic agents in terms of electrophysiological actions on refractoriness and conduction in a 7-day-old canine model of myocardial infarction. Sustained monomorphic VT was reproducibly induced in 26 dogs by a premature stimulation method from the right ventricle. Class I drugs (disopyramide, aprindine, flecainide) prevented VT induction in 5 of 13 dogs, and propranolol and E-4031 prevented it in 6 of 6 and 6 of 7 dogs, respectively. The effective refractory period (ERP) was determined at 47 epicardial sites overlying the infarct in each experiment by a S1S2 method. The standard deviation (SD) of the mean ERP of these sites was used as an index of ERP dispersion. The extent of ERP prolongation produced by class I drugs and E-4031 was significantly more marked than that produced by propranolol. However, the SD was increased by class I drugs and E-4031, but not by propranolol. Class I drugs increased the ERP dispersion mainly by an effect on the transmural infarct zone in which the control ERP was more prolonged than in the normal zone. E-4031 tended to prolong the ERP in both the normal and infarct zones, and had a minimal tendency to increase ERP dispersion. In contrast, propranolol decreased the ERP dispersion between zones. Conduction velocity calculated by epicardial mapping was significantly decreased by flecainide, but not by E-4031. We conclude that the antiarrhythmic effect of E-4031 depends largely on its ability to prolong refractoriness without suppressing conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Anti-Arrhythmia Agents; Aprindine; Arrhythmias, Cardiac; Disease Models, Animal; Disopyramide; Dogs; Electrophysiology; Flecainide; Myocardial Infarction; Piperidines; Potassium Channel Blockers; Pyridines; Tachycardia, Ventricular

1993
Class III actions in an experimental model of ventricular tachycardia.
    European heart journal, 1993, Volume: 14 Suppl H

    Simplified models of re-entry may help in our understanding of the electrophysiologic effects of class III drugs. In a model of re-entrant ventricular tachycardia around a ring of epicardium in Langendorff-perfused rabbit hearts, the electrophysiologic effects of class III antiarrhythmic drugs were studied and compared to those of class I drugs. Class III drugs were effective in terminating fast re-entrant ventricular tachycardias. Prolongation of the refractory period without affecting conduction velocity resulted in a closure of the excitable gap and collision of the head of the propagating impulse against its own tail of refractoriness. In slow ventricular tachycardias, despite a similar increase in refractory period, the excitable gap remained large enough to allow perpetuation of the tachycardia.

    Topics: Animals; Anti-Arrhythmia Agents; Chromans; Dose-Response Relationship, Drug; Female; Heart Conduction System; Male; Perfusion; Piperidines; Rabbits; Tachycardia, Ventricular

1993
Efficacy of class 1C antiarrhythmic agents in patients with inducible ventricular tachycardia refractory to therapy with class 1A antiarrhythmic drugs.
    Journal of clinical pharmacology, 1993, Volume: 33, Issue:7

    The efficacy of class 1C antiarrhythmic agents was determined in 36 patients with inducible sustained monomorphic ventricular tachycardia during baseline electrophysiology study (EPS), who continued to have inducible monomorphic ventricular tachycardia during EPS on class 1A antiarrhythmic therapy. Of 12 patients who partially responded to class 1A drugs, 11 (91.7%) continued to have a partial response during EPS on class 1C therapy, whereas one patient did not respond. Of 24 nonresponders to class 1A therapy, 2 (8.3%) responded during EPS on class 1C therapy, 7 (29.2%) partially responded, and 15 (62.5%) did not respond. In the 24 nonresponders to class 1A therapy, 9 of 17 patients (53%) with left ventricular ejection fraction (EF) > or = 30% responded or partially responded to class 1C therapy, compared with none of 7 patients with EF < 30% (P < .05). The EPS on class 1C agents in patients who fail to respond to class 1A therapy may be warranted only in those with EF > or = 30%.

    Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Benzeneacetamides; Electric Stimulation; Encainide; Female; Flecainide; Humans; Male; Middle Aged; Piperidines; Quinidine; Retrospective Studies; Stroke Volume; Tachycardia, Ventricular

1993
Specific IK1 blockade: a new antiarrhythmic mechanism? Effect of RP58866 on ventricular arrhythmias in rat, rabbit, and primate.
    Circulation, 1993, Volume: 87, Issue:6

    The effectiveness of blockade of the inwardly rectifying K+ current (IK1) in prevention of arrhythmias is unknown. We have examined the antiarrhythmic potential of a new selective IK1 blocker, RP58866, in rat, rabbit, and primate (marmoset) isolated hearts in the settings of acute ischemia and reperfusion.. In concentration-response studies (n = 12 per group), the drug reduced ischemia-induced ventricular fibrillation (VF) in rat from control incidence of 100 to 50%, 17% (p < 0.05), and 0% (p < 0.05) at 1, 3, and 10 mumol/L, respectively. RP58866 produced significant bradycardia at the 3- and 10-mumol/L concentrations and significant QT interval widening at all three concentrations (p < 0.05). When rat hearts (n = 12 per group) were paced (5 Hz) via the left atrium to prevent bradycardia, the antiarrhythmic effects of 10-mumol/L RP58866 were unmodified (ischemia-induced VF incidence was reduced by drug from 83% in control hearts to 8%; p < 0.05). Similarly, pacing did not prevent the drug's QT-widening activity at 90% repolarization (QT90 was 64 +/- 3 msec in control hearts versus 128 +/- 17 msec in the presence of 10 mumol/L of drug after 10 minutes of ischemia; p < 0.05). These values are similar to equivalent values in unpaced hearts (65 +/- 3 msec in control hearts versus 159 +/- 15 msec with 10 mumol/L of drug; p < 0.05). In separate groups of rat hearts (n = 10 per group) subjected to 10 minutes of ischemia, reperfusion-induced VF incidence was reduced from 90% in control hearts to 10% (p < 0.05), 0% (p < 0.05), and 0% (p < 0.05) by 1-, 3-, and 10-mumol/L RP58866. To examine whether drug actions were species-specific, we performed further studies in rabbit and primate using the middle concentration of RP58866 (3 mumol/L). Ischemia-induced VF incidence was too low in these species to assess the effects of the drug. However, RP58866 widened QT interval (p < 0.05), slowed heart rate (p < 0.05), and reduced the incidence of reperfusion-induced VF from 67% to 8% (p < 0.05) in rabbit. Furthermore, in the more clinically relevant primate species (marmoset; n = 9-12 per group), RP58866 (3 mumol/L) abolished ischemia-induced VT (36% incidence in control hearts; p < 0.05) and significantly reduced the incidence of ischemia-induced ventricular premature beats from 91% to 33% (p < 0.05). The drug was also effective against reperfusion VF in primates (incidence reduced from 64% in control hearts to 11%; p < 0.05). As in rat and rabbit, RP58866 significantly widened QT interval in primate and caused bradycardia before and during ischemia. RP58866 had no significant influence on coronary flow in any species. Finally, in further studies on rat, QT widening by RP58866 was found to persist relatively unmodified in nonischemic hearts perfused with solution containing K+. RP58866, a selective IK1 blocker, is a potent and efficacious new antiarrhythmic drug in ischemia and reperfusion in rat, rabbit, and primate. When tested in rat, pharmacological activity was undiminished by cardiac pacing or elevation of extracellular K+.

    Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Callithrix; Cardiac Pacing, Artificial; Chromans; Electrocardiography; Heart; Male; Myocardial Reperfusion Injury; Piperidines; Potassium Channels; Rabbits; Rats; Rats, Wistar; Tachycardia, Ventricular; Ventricular Fibrillation

1993