Dofetilide reduces the incidence of ventricular fibrillation during acute myocardial ischaemia. A randomised study in pigs.
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.
Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Denmark.
H R
HR
Andersen
H
H
Wiggers
L L
LL
Knudsen
I
I
Simonsen
P E
PE
Thomsen
N
N
Christiansen
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004562:Electrocardiography; D017202:Myocardial Ischemia / Q000150:complications*; D010627:Phenethylamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D015221:Potassium Channels; D013449:Sulfonamides; C063533:dofetilide