BIOMAT Database Logo BIOMAT Database Logo

The effect of bidisomide (SC-40230), a new class Ia/Ib antiarrhythmic agent, on defibrillation energy requirements in dogs with healed myocardial infarctions. 1993

A M Hackett, and P Gardiner, and S M Garthwaite
Department of Clinical Research, Searle Research and Development, Skokie, Illinois 60077.

Bidisomide is a Class Ia/Ib antiarrhythmic agent with activity against ventricular and supraventricular arrhythmias. The potential for bidisomide to increase defibrillation threshold (DFT) was tested in anesthetized dogs with healed left ventricular infarcts (> or = 10 days). Defibrillation patches were attached to each ventricle and shocks were delivered via an external cardioverter/defibrillator. Three groups were studied: placebo (saline), canine therapeutic bidisomide (TB, 2-5 micrograms/mL plasma concentration) and supratherapeutic bidisomide (STB, 6-14 micrograms/mL). Each animal received only one treatment. An abbreviated DFT curve was determined before and after treatment. Heart rate, blood pressure, PR, QRS, infarct size, and hematocrit were also measured before and after treatment. DFT was significantly increased (average +3 to +5 joules [J], P < 0.05) by TB and STB. TB (5/5) did not increase DFT beyond 40 J. In 6/7 experiments, STB did not increase DFT beyond 40 J. Placebo (n = 6) had no significant effect on DFT. Infarct size (mean = 11% of the left ventricle) was not significantly different between groups. Heart rate and QRS were not significantly altered but blood pressure was significantly decreased (16%-31% systolic, 29%-45% diastolic) and hematocrit was significantly increased (19% to 25%) in all groups. PR was significantly increased by STB only. CONCLUSIONS therapeutic and supratherapeutic doses of bidisomide slightly but significantly increased DFT (3-5 J) in a canine infarcted heart model.

UI MeSH Term Description Entries
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D010880 Piperidines A family of hexahydropyridines.
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004554 Electric Countershock An electrical current applied to the HEART to terminate a CARDIAC ARRHYTHMIA. Cardiac Electroversion,Cardioversion,Defibrillation, Electric,Electroversion, Cardiac,Electrical Cardioversion,Electroversion Therapy,Therapy, Electroversion,Cardiac Electroversions,Cardioversion, Electrical,Cardioversions,Cardioversions, Electrical,Countershock, Electric,Countershocks, Electric,Defibrillations, Electric,Electric Countershocks,Electric Defibrillation,Electric Defibrillations,Electrical Cardioversions,Electroversion Therapies,Electroversions, Cardiac,Therapies, Electroversion
D004562 Electrocardiography Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY. 12-Lead ECG,12-Lead EKG,12-Lead Electrocardiography,Cardiography,ECG,EKG,Electrocardiogram,Electrocardiograph,12 Lead ECG,12 Lead EKG,12 Lead Electrocardiography,12-Lead ECGs,12-Lead EKGs,12-Lead Electrocardiographies,Cardiographies,ECG, 12-Lead,EKG, 12-Lead,Electrocardiograms,Electrocardiographies, 12-Lead,Electrocardiographs,Electrocardiography, 12-Lead
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000889 Anti-Arrhythmia Agents Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic
D014693 Ventricular Fibrillation A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST. Fibrillation, Ventricular,Fibrillations, Ventricular,Ventricular Fibrillations

Related Publications

A M Hackett, and P Gardiner, and S M Garthwaite
Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.
April 1992, Clinical pharmacology and therapeutics,
A M Hackett, and P Gardiner, and S M Garthwaite
Absorption and disposition of a new antiarrhythmic agent bidisomide in man.
November 1993, Pharmaceutical research,
A M Hackett, and P Gardiner, and S M Garthwaite
Mexiletine has no effect on defibrillation energy requirements in dogs.
December 1994, Pacing and clinical electrophysiology : PACE,
A M Hackett, and P Gardiner, and S M Garthwaite
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.
January 1995, Heart and vessels,
A M Hackett, and P Gardiner, and S M Garthwaite
Effects of a new class I antiarrhythmic drug bidisomide on canine ventricular arrhythmia models.
February 1993, Molecular and cellular biochemistry,
A M Hackett, and P Gardiner, and S M Garthwaite
Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation.
May 1989, Circulation,
A M Hackett, and P Gardiner, and S M Garthwaite
Isoproterenol increases defibrillation energy requirements in dogs.
February 1992, Journal of cardiovascular pharmacology,
A M Hackett, and P Gardiner, and S M Garthwaite
Effects of the novel class Ia and class III antiarrhythmic agent RS-87337 on myocardial conduction in the anaesthetised dog.
January 1988, Archives internationales de pharmacodynamie et de therapie,
A M Hackett, and P Gardiner, and S M Garthwaite
Effect of cibenzoline, a class ia antiarrhythmic agent, on left ventricular diastolic function in hypertrophic cardiomyopathy.
September 2001, Cardiovascular drugs and therapy,
A M Hackett, and P Gardiner, and S M Garthwaite
Membrane potential-dependent effects of SC-36602, a new class I antiarrhythmic agent on cardiac action potentials.
January 1987, Journal of cardiovascular pharmacology,
Copied contents to your clipboard!