Evaluation of the antiarrhythmic effects of Verapamil,propranolol and lidocainein Adrenaline induced cardiac arrhythmias in dogs
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, xvi 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 xvii 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 xviii 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.