Cardiac Arrhythmias Following Intravenous Nicotine: Experimental Study in Dogs

Background: Nicotine, the active agent in tobacco, is released into the circulation during cigarette smoking. It elevates plasma catecholamines, heart rate, and arterial blood pressure; produces coronary spasm; and increases myocardial work and oxygen demand with con comitant reduction in oxygen supply. This may generate cardiac arrhythmias that might con tribute to an increased incidence of sudden death due to smoking. It is hypothesized that acute administration of nicotine will induce cardiac arrhythmias, and this experimental study was planned with an aim to assess arrhythmogenic activity as a result of acute administration of nicotine. Methods: Nicotine was administered in different doses intravenously in 16 anesthesized dogs, and 52 experiments were carried out at weekly intervals. In each experiment, continu ous electrocardiograph rhythm strip records were obtained for 30 minutes before and follow ing anesthesia and after nicotine administration. They were scrutinized by two experienced electrocardiographers at intervals of 1, 2, 3, 4, 5, 10, 15, and 30 minutes. Results: Data revealed nonsignificant arrhythmias with doses of 2.5, 5.0, and 10.0 mg/kg of intravenous nicotine. The dose of 50 μg/kg induced supraventricular arrhythmias, atrioven tricular junctional arrhythmias, and ventricular arrhythmias. Supraventricular bradycardia in 30 (83%; P < .000 1), supraventricular arrhythmia in 30 (83%; P < .0001), sinus arrest in 18 (50%; P < .003). atrial ectopics in 24 (67%; P < .0004), and atrial tachycardia in 9 experi ments (25%; P < .021). These results were statistically significant. In 18 experiments, sinus arrest was observed to be missing P waves and QRS complexes for a period corresponding to 4:1-10:1 SA block, lasting 2-6 seconds, within 3 seconds of injection. Occurrence of wan dering pacemaker was observed in 6 experiments, atrial flutter in 2, and atrial fibrillation in 2, but these incidents were not significant. Atrioventricular junctional arrhythmias consisted of escape beats in 9 subjects (25%; P < .02), premature contractions in 12 (33%; P < .005), first-degree heart block in 9 (25%; P < .02), second degree heart block in 9 (25%; P < .02) and atrioventricular dissociation in 9 (25%; P < .02). All arrhythmias in this category were significant. Ventricular arrhythmias consisted of ventricular premature contractions that were unifocal in 32 subjects (89%; P < .0001), multifocal in 30 (83%; P < .0001), bigeminy in 28 (78%; P < .0003), trigeminy in 18 (50%; P < .003), interpolated in 15 (42%; P < .004), and salvos in 18 (50%; P < .003). Sustained ventricular tachycardias (> 30 beats) in 12 experi ments (33%; P < .005) proved significant. The dose of 100 μg/kg induced fatal ventricular flutter and ventricular fibrillation. The dog expired and experiments with that dose were not repeated. Conclusion: Data reveal dose-dependent arrhythmogenecity of nicotine in dogs. Smaller doses of nicotine did not produce significant arrhythmias. Higher doses, bioequivalent to smoking two standard cigarettes, may generate cardiac arrhythmias of simple to severe nature. Further work in human beings may confirm whether nicotine in cigarette smoke will generate similar cardiac arrhythmias especially in patients with autonomic imbalance and/or compromised and ischemic myocardium.