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Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release

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Abstract

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.

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Acknowledgements

We thank Karen Beatty, Jessica Nystoriak, and Dan Riggs for technical support and assistance in ECG procurement.

Funding

Research reported in this publication was supported by the National Heart, Lung, And Blood Institute (NHLBI) of the National Institutes of Health (award numbers R01HL147343, HL071739, R01HL147343, N01-HC-95159, and N01-HC-95169), the AHA Tobacco Regulation and Addiction Center (A-TRAC), and FDA Center for Tobacco Products (CTP) (P50HL120163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. C.A. was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Physiology, University of Louisville, Louisville, KY, USA

    Affan B. Irfan & Alex P. Carll

  2. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

    Affan B. Irfan

  3. Diabetes and Obesity Center, University of Louisville, Louisville, KY, USA

    Affan B. Irfan, Claudia Arab, Andrew P. DeFilippis, Pawel Lorkiewicz, Rachel J. Keith, Zhengzhi Xie, Aruni Bhatnagar & Alex P. Carll

  4. Graduate Program in Cardiology, Federal University of São Paulo, São Paulo, Brazil

    Claudia Arab

  5. Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY, USA

    Andrew P. DeFilippis, Pawel Lorkiewicz, Rachel J. Keith, Zhengzhi Xie, Aruni Bhatnagar & Alex P. Carll

  6. American Heart Association-Tobacco Regulatory and Addiction Center, Dallas, TX, USA

    Andrew P. DeFilippis, Pawel Lorkiewicz, Rachel J. Keith, Zhengzhi Xie, Aruni Bhatnagar & Alex P. Carll

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Contributions

Concept/design: ABI, AB, APC. Data analysis/interpretation: ABI, AB, APC. Drafting article: ABI, AB, APC, APD. Critical revision of article: ABI, AB, APC, APD. Data collection: ABI, CA, PL, ZX, APC.

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Correspondence to Alex P. Carll.

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Irfan, A.B., Arab, C., DeFilippis, A.P. et al. Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release. Cardiovasc Toxicol 21, 169–178 (2021). https://doi.org/10.1007/s12012-020-09610-5

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  • DOI: https://doi.org/10.1007/s12012-020-09610-5

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