Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release

Cardiovasc Toxicol. 2021 Feb;21(2):169-178. doi: 10.1007/s12012-020-09610-5. Epub 2020 Oct 12.


Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.

Keywords: Atrioventricular; Catecholamines; Cigarette; Cotinine; Dopamine; Electrocardiography; P wave; PR interval; PR segment; Smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Adult
  • Arrhythmias, Cardiac / etiology*
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / urine
  • Biomarkers / urine
  • Cotinine / urine
  • Dopamine / urine*
  • Electrocardiography
  • Ex-Smokers
  • Female
  • Heart Conduction System / physiopathology*
  • Heart Disease Risk Factors
  • Heart Rate*
  • Humans
  • Male
  • Middle Aged
  • Non-Smokers
  • Smokers*
  • Smoking / adverse effects*
  • Smoking / physiopathology
  • Smoking / urine
  • Urinalysis


  • Biomarkers
  • Cotinine
  • Dopamine