Evaluation of the antiarrhythmic effects of Verapamil,propranolol and lidocainein Adrenaline induced cardiac arrhythmias in dogs
Abstract
Cardiac arrhythmias can occur in any condition such
as coronary heart disease or hypoxia in which impulse
formation is enhanced, or in which impulse conduction is
impaired, or in which a combination of these factors are
present. Enhancement of automaticity of latent pacemaker
cells by increased sympathetic discharge is a common cause
of arrhythmias such as supraventricular and ventricular
arrhythmias. Management of these arrhythmias calls for a
rational use of drugs with proper diagnosis as use of the wrong
drug will aggravate the existing arrhythmia and even lead to
death. The purpose of this study was to evaluate two older
antiarrhythmic drugs (propranolol and lidocaine) and a new
antiarrhythmic drug (verapamil) in the treatment of
adrenaline induced arrhythmias and observe their effects on
electrocardiographic (ECG) parameters, blood pressure, some
biochemical and haematologic parameters.
Twenty adult mongrel dogs of either sex were used
in the first study. The dogs were divided randomly into 4
groups of 5 dogs each (n=5). The dogs were anaesthetized
with halothane and then pretreated with the drugs (verapamil
0.1 mg/kg bwt., propranolol 0.06 mg/kg bwt., and lidocaine 4
rug/kg bwt.) while the controls received sterile physiological
saline. All drug administrations were done intravenously using
the jugular vein. Adrenaline (4 Jlg/kg bwt.) was administered
10 minutes after drug pretreatments. Blood was collected
from the jugular vein for haematology. ECG recordings were
made before drug pretreatments, after drug pretreatments,
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after adrenaline administration, and 30 minutes after the first
recording.
In another different study, twenty adult mongrel
dogs were used in the experiment. The dogs were also
randomly divided into 4 groups of 5 dogs each (n=5). The
dogs were anaesthetized with halothane and then received
similar drug pretreatments as in the first study except
propranolol was given at a dose of 0.5 mg/kg bwt. while the
controls received sterile physiological saline. Adrenaline (4
Ilg/kg· bwt.) was administered 5 minutes after drug
pretreatments. Blood was collected from the jugular vein at
designated time intervals for evaluation of serum levels of
calcium, a-hydroxybutyrate dehydrogenase and lactic
dehydrogenase enzymes. Blood pressure was monitored via a
catheter placed in the femoral artery. ECG recordings were
made before drug pretreatments, after drug pretreatments,
after adrenaline administration, and 30 minutes after the first
. ECG recording.
In the first study drug pretreatments were able to
prevent death occurring while 3 dogs died in the control
group. In all the dogs that died, ventricular fibrillation which
was preceded by ventricular tachycardia was observed. The
predominant arrhythmias that occurred were ventricular
premature beats, ventricular tachycardia, and second degree
heart block. The mean P wave amplitude (0.277±0.11 mV) of
the lidocaine pretreated dogs was higher (p<0.05) than those
of propranolol (O.221±O.1 mV), verapamil (O.195±O.08 mV)
and control (0.148±.09 mV). Propranolol pretreated dogs
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showed an increased S-T duration while for lidocaine
pretreated dogs there was a decrease on adrenaline
administration (p<O.05). Lidocaine pretreatment was able to
prevent the increase in the total leucocyte count that
occurred in the controls (p<O.05). Mean total neutrophil
percentage for the lidocaine and verapamil pretreated groups
were significantly less than (p<O.05) those of the control
group.
In the second study propranolol pretreatment
protected dogs from death after adrenaline administration. In
control group 3 dogs died, in verapamil pretreated group 2
dogs died whereas 1 dog died in the lidocaine pretreated
group. In all the animals that died ventricular fibrillations
which we~e preceded by ventricular tachycardia occurred.
The predominant arrhythmias that occurred were similar to
those observed in the first study except in one propranolol
pretreated dog in which sinus arrest occurred. There was
significant difference (p<O.05) in the P wave amplitude of the
verapamil pretreated group (O.19±O.06 mV) compared to the
propranolol pretreated (O.14±O.05 mV) and lidocaine
pretreated group (O.14±O.06 mV). There was a significant
difference (p<O.05) in mean QRS complex between control
(O.041±O.OOl sec.) and lidocaine pretreated dogs
(O.044±O.005sec.).There was an apparent increase for T wave
amplitude in all the groups, however, verapamil treated
groups significantly increased (p<O.05) from O.163±O.09 mV
to O.317±O.04 mV. Adrenaline administration caused
significant increase in arterial blood pressure in all the
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experimental groups (p<O.05). The arrhythmias, especially
second degree heart block and the ventricular arrhythmias
when they occurred in runs were associated with decreases in
the elevated arterial pressures.
Increased trend in the serum levels of the enzyme
lactic dehydrogenase and a- hydroxybutyrate dehydrogenase
occurred within the first 8 hours in all the groups. However,
lidocaine pretreated dogs had higher increase (p<0.05)
compared to verapamil pretreated dogs. There was no
difference in the levels of calcium between the drug
pretreated groups and the control dogs.
The results obtained in this study suggests that
propranolol (0.5 mg/kg bwt.) and lidocaine are superior to
verapamil in the control of adrenaline induced ventricular
arrhythmias in the dog at the dosages used. Pretreatments
with the drugs at the dosages used in the study did not
prevent increase in arterial blood pressure induced by
adrenaline. Drug pretreatments did not have any clinical
significant effects on the ECG parameters. Drug pretreatments
did not have much effect on the levels of serum calcium and
the enzymes a-hydroxybutyrate dehydrogenase and lactic
dehydrogenase.
Citation
Kitaa, J.M.A., 1990Publisher
Department of Public Health, pharmacology and Toxicology