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Dofetilide reduces the incidence of ventricular fibrillation during acute myocardial ischaemia. A randomised study in pigs. 1994

H R Andersen, and H Wiggers, and L L Knudsen, and I Simonsen, and P E Thomsen, and N Christiansen
Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Denmark.

OBJECTIVE The aim was to investigate whether dofetilide, a new selective cardiac potassium channel blocker, would reduce the incidence of ischaemia induced ventricular fibrillation in closed chest pigs. METHODS A randomised, blinded, and placebo controlled study was performed in 32 closed chest pigs with a body weight of 70-90 kg. The animals were given a dofetilide/placebo bolus of 25 micrograms.kg-1 over a 10 min period followed by a maintenance dose of 12.5 micrograms.kg-1.h-1 for the next 130 min. Electrocardiograms were recorded during sinus rhythm and during atrial pacing, before (t0) and 20 min (t20) after the beginning of drug treatment. Twenty minutes after the start of drug treatment, acute myocardial ischaemia was induced by inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon placed in the left anterior descending coronary artery proximal to the first diagonal branch. If ventricular fibrillation occurred during the 2 h ischaemia period the balloon was deflated and defibrillation attempted by dc shocks (360 joules) up to a maximum of 10 shocks. RESULTS Basal characteristics for the dofetilide group (n = 16) and the placebo group (n = 16) were similar: body weight 76.1(SD 5.4) kg v 75.4(4.4) kg; heart weight 296(29) g v 302(43) g; and heart rate (RR interval) 854(261) ms v 800(307) ms. During atrial pacing 100 beats.min-1 the paced QT interval (QTp) measured at t0 in the dofetilide group and the placebo group were similar, at 335(36) ms v 330(31) ms, respectively. During drug treatment (t20) the QTp interval increased to 412(38) ms in the dofetilide group (p < 0.001) whereas a much smaller increase to 341(32) ms was observed in the placebo group (p < 0.05). The heart rate and ST elevation in the two groups were similar during coronary artery occlusion. During the 2 h ischaemic period, ventricular fibrillation occurred in 6/16 (38%) of the dofetilide treated pigs, and in 13/16 (81%) of the placebo treated pigs (p < 0.01). Defibrillation was successful in 5/6 (83%) and 6/13 (46%) of the animals, respectively (p = 0.3). CONCLUSIONS Dofetilide significantly reduces the incidence of ischaemia induced ventricular fibrillation in closed chest pigs.

UI MeSH Term Description Entries
D010627 Phenethylamines A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed) Phenylethylamines
D002304 Cardiac Pacing, Artificial Regulation of the rate of contraction of the heart muscles by an artificial pacemaker. Pacing, Cardiac, Artificial,Artificial Cardiac Pacing,Artificial Cardiac Pacings,Cardiac Pacings, Artificial,Pacing, Artificial Cardiac,Pacings, Artificial Cardiac
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
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
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
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
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
D015221 Potassium Channels Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits. Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel

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