Nicotine, Heart Rhythm and Myocarditis: The Research

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1. Research at a Glance
2. The Papers
3. PubMed Topic Searches
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Research at a Glance

What kind of study each paper on this page is, and when the papers were published. Hover over a bar for its count.

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The Papers (26)

Newest first. Study types on this page — Human trial: 2 · Human observational study: 1 · Review: 2 · Animal study: 12 · Cell study: 8 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine Induces Fetal Cardiac Dysfunction by Promoting Cardiomyocyte Apoptosis Through Regulating the KCTD10-Notch Signaling

Animal study, 2025. Researchers exposed pregnant mice to nicotine and studied fetal heart effects, along with isolated heart muscle cells in the lab. Nicotine exposure lowered fetal weight, worsened heart function, and reduced pregnancy success rates in the mice; in isolated heart cells, nicotine increased cell death and inflammation. The study found nicotine does this by lowering a protein called KCTD10 and turning on a signaling pathway called Notch, and blocking that pathway in the lab reversed the heart cell damage.

Zhong L, Yang X, Zhang H et al. (2025). Nicotine Induces Fetal Cardiac Dysfunction by Promoting Cardiomyocyte Apoptosis Through Regulating the KCTD10-Notch Signaling. Int Heart J. — PubMed PMID: 40634059 · doi:10.1536/ihj.24-427

In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway

Animal study, 2024. Pregnant rats were exposed to repeated nicotine aerosol puffs (similar to vaping) from early to late pregnancy, and their adult offspring (6 months old) were studied. The offspring exposed to nicotine before birth had worse heart damage and heart function problems when their hearts were deprived of blood flow, linked to changes in several heart signaling pathways (angiotensin II receptor, TGF-beta, reactive oxygen species, and others) in heart muscle cells.

Yu W, Chen Z, Li Y et al. (2024). In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway. Reprod Toxicol. — PubMed PMID: 38945500 · doi:10.1016/j.reprotox.2024.108650

Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart

Animal study, 2024. Rabbits were given chronic nicotine (transdermal patches, 21 mg/day for 28 days) or control patches, then had their isolated hearts studied with optical mapping of electrical activity and calcium handling. Nicotine-exposed hearts had a higher baseline heart rate, developed abnormal beat-to-beat electrical and calcium alternans more easily, had fewer sympathetic nerve fibers in the heart muscle, and showed altered responses to norepinephrine stimulation, suggesting nicotine remodels the heart's nerve supply and electrical stability in ways that could raise arrhythmia risk with longer exposure.

Guevara A, Smith CER, Caldwell JL et al. (2024). Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart. Am J Physiol Heart Circ Physiol. — PubMed PMID: 38551482 · doi:10.1152/ajpheart.00749.2023

Nicotine Ingestion Reduces Heart Rate Variability in Young Healthy Adults

Human trial, 2022. This randomized controlled trial gave 4 mg of nicotine by mouth to 80 young, healthy non-smokers (40 men and 40 women) and measured heart rate variability, a marker of how flexibly the heart's rhythm adjusts. Nicotine reduced heart rate variability in both men and women, and the size of the effect did not differ between the sexes. The authors concluded that nicotine at doses of 4 mg or more is harmful to the heart of young people.

Guo QN, Wang J, Liu HY et al. (2022). Nicotine Ingestion Reduces Heart Rate Variability in Young Healthy Adults. Biomed Res Int. — PubMed PMID: 35028314 · doi:10.1155/2022/4286621

Adverse effects of fetal exposure of electronic-cigarettes and high-fat diet on male neonatal hearts

Animal study, 2021. Researchers fed pregnant mice a high-fat diet and exposed them to either saltwater mist or e-cigarette aerosol containing 2.4% nicotine for most of the pregnancy, then examined the hearts of the male offspring. Pups exposed to the e-cigarette aerosol plus the high-fat diet showed more heart muscle cell death on days 1, 3 and 14 after birth, along with increased oxidative stress and changes in proteins that control cell death. Electron microscope images at day 14 showed damaged cell nuclei, disorganized muscle fibers and enlarged mitochondria, which the authors describe as signs of heart muscle disease. These results are only in mice, and the authors say the damage may lead to long-term heart problems in adulthood.

Hasan KM, Munoz A, Tumoyan H et al. (2021). Adverse effects of fetal exposure of electronic-cigarettes and high-fat diet on male neonatal hearts. Exp Mol Pathol. — PubMed PMID: 33212125 · doi:10.1016/j.yexmp.2020.104573

Nicotine induces cardiac toxicity through blocking mitophagic clearance in young adult rat

Animal study, 2020. Researchers gave young adult rats nicotine over a long period to see how it affects the heart. The nicotine damaged heart muscle cells, increased scarring (fibrosis) in the heart, and clearly weakened heart function compared with untreated rats. The authors found that nicotine raised harmful reactive oxygen molecules, which blocked the cell's normal clean-up of damaged mitochondria (the cell's energy units) and set off a cell-death pathway. These results come from rats only, and the authors suggest nicotine may harm heart muscle in young adults as well.

Jia G, Meng Z, Liu C et al. (2020). Nicotine induces cardiac toxicity through blocking mitophagic clearance in young adult rat. Life Sci. — PubMed PMID: 32663572 · doi:10.1016/j.lfs.2020.118084

Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression

Cell study, 2020. This study tested nicotine on heart muscle cells taken from newborn mice and grown in the lab. Low doses of nicotine increased autophagy, the cell's own clean-up and recycling process, and reduced cell death, but high doses did the opposite: they blocked autophagy and increased cell death. The low-dose effects depended on a protective protein called heme oxygenase-1 (HO-1) and on the alpha-7 nicotinic receptor, and low-dose nicotine also lessened damage caused by a fatty acid called palmitic acid. These results come only from cells in a dish, not from animals or people.

Xing R, Cheng X, Qi Y et al. (2020). Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression. Biochem Biophys Res Commun. — PubMed PMID: 31813548 · doi:10.1016/j.bbrc.2019.11.086

Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte

Animal study, 2019. This study looked at how nicotine affects insulin response in heart muscle cells grown in the lab and in mice. In the heart cells, nicotine raised levels of reactive oxygen species (harmful oxygen-based molecules) and reduced the glucose the cells took up in response to insulin. It also lowered the activity of Nrf2, a protein that helps protect cells, and pretreatment with the antioxidant N-acetyl-L-cysteine reversed these effects. Mice given nicotine developed glucose intolerance and impaired insulin tolerance, with similar changes in their heart tissue; these results come only from cells and mice.

Li Z, Xu W, Su Y et al. (2019). Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte. Mol Cell Endocrinol. — PubMed PMID: 31315024 · doi:10.1016/j.mce.2019.110507

Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice

Animal study, 2019. This study in mice bred to develop clogged arteries exposed the animals for 12 weeks to e-cigarette vapor with 2.4% nicotine, e-cigarette vapor without nicotine, or a saltwater mist. Only the mice given vapor with nicotine showed weaker heart pumping, signs of heart muscle damage under the microscope, more oxidative stress, more mutations in mitochondrial DNA, and changes in genes tied to metabolism, daily body rhythms and inflammation. These mice also had more artery plaque than the mice given the saltwater mist. These results come from mice only, and the authors concluded that e-cigarettes with nicotine harm heart function in mice.

Espinoza-Derout J, Hasan KM, Shao XM et al. (2019). Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice. Am J Physiol Heart Circ Physiol. — PubMed PMID: 31172811 · doi:10.1152/ajpheart.00738.2018

Nicotine induces H9C2 cell apoptosis via Akt protein degradation

Cell study, 2017. Researchers exposed rat heart muscle cells grown in the lab (the H9C2 cell line) to nicotine at 0, 10 and 100 µM for 48 hours. Nicotine made more of the cells undergo programmed cell death (apoptosis). It also lowered levels of Akt, a protein that helps cells survive, and the higher the dose, the bigger the drop. The authors found that nicotine raised levels of another protein, TTC3, which appears to tag Akt for breakdown. When they added extra Akt or blocked TTC3, more cells survived. These results come only from cells in a dish, not from animals or people.

Huang C, Guo X, Zhao H et al. (2017). Nicotine induces H9C2 cell apoptosis via Akt protein degradation. Mol Med Rep. — PubMed PMID: 28849146 · doi:10.3892/mmr.2017.7331

Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine

Cell study, 2017. Researchers tested nicotine at 4, 40 and 400 nM, levels they describe as clinically relevant, on heart muscle cells taken from the upper chambers (atria) of rats. They measured a potassium current that is linked to atrial fibrillation, a common irregular heart rhythm. At 40 and 400 nM, nicotine raised the part of this current that is always switched on, with the largest effect at 40 nM (roughly a 100% increase); 4 nM had little effect on average, and adding alcohol did not increase the effect further. Nicotine had a two-way effect on the part of the current triggered by acetylcholine, raising it in cells where it started small and lowering it where it started large. These results come only from isolated rat cells.

Bébarová M, Matejovič P, Švecová O et al. (2017). Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine. Naunyn Schmiedebergs Arch Pharmacol. — PubMed PMID: 28160016 · doi:10.1007/s00210-017-1341-z

Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis

Animal study, 2017. Researchers gave adult male mice either a normal diet or a high-fat diet for 16 weeks, along with twice-daily injections of nicotine or salt water. In mice on the high-fat diet, nicotine caused a large increase in the death of heart muscle cells. This was fully prevented by a drug that blocks nicotine's receptors. The cell death came with more oxidative stress, activation of a cell-death pathway, and switching off of an energy-sensing enzyme called AMPK. These results come from mice only.

Sinha-Hikim I, Friedman TC, Falz M et al. (2017). Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell Tissue Res. — PubMed PMID: 27917437 · doi:10.1007/s00441-016-2536-1

Addictive drugs, arrhythmias, and cardiac inward rectifiers

Review, 2017. This review looks at addictive drugs, including alcohol and nicotine, which have been reported to disturb the heart's rhythm. It summarizes what is currently known about how these drugs may trigger irregular heartbeats, focusing on a group of potassium channels in heart cells called inward rectifier channels. The authors say important data are still missing and call for more research so that the risk these drugs pose to heart rhythm is better understood.

Bébarová M, Horáková Z, Kula R (2017). Addictive drugs, arrhythmias, and cardiac inward rectifiers. Europace. — PubMed PMID: 27302393 · doi:10.1093/europace/euw071

Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3

Animal study, 2016. This study used mice infected with coxsackievirus B3, a virus that causes inflammation of the heart muscle (viral myocarditis), to test nicotine acting on the alpha7 nicotinic receptor. Compared with mice given a drug that blocks this receptor, mice given nicotine survived more often, had less heart-muscle inflammation and better pumping function of the left ventricle, and had lower levels of the inflammatory signals TNF-alpha, IL-1beta, IL-6 and IL-17A. Nicotine had no significant antioxidant or antiviral effect. These results are only in mice; the authors suggest that drugs acting on this receptor may be a possible new approach for myocarditis.

Li-Sha G, Jing-Lin Z, Li L et al. (2016). Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3. Life Sci. — PubMed PMID: 26851533 · doi:10.1016/j.lfs.2016.02.003

Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

Animal study, 2015. This study tested nicotine, which acts on the alpha7 nicotinic receptor (a receptor linked to calming inflammation), in mice infected with coxsackievirus B3, a virus that causes inflammation of the heart muscle (viral myocarditis). Mice received 0.1, 0.2 or 0.4 mg/kg of nicotine three times a day for 7 or 14 days. Survival at day 14 rose with the dose and was markedly higher in the 0.2 and 0.4 mg/kg groups than in untreated infected mice; the high dose reduced heart inflammation, improved the heart's pumping function and lowered the inflammatory signals TNF-α, IL-1β, IL-6 and IL-17A. These results are in mice only; the authors suggest drugs that activate the alpha7 receptor may be a promising approach for patients with viral myocarditis.

Li-Sha G, Jing-Lin Z, Guang-Yi C et al. (2015). Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3. Sci Rep. — PubMed PMID: 26507386 · doi:10.1038/srep15895

Downregulation of miR-133 via MAPK/ERK signaling pathway involved in nicotine-induced cardiomyocyte apoptosis

Cell study, 2014. This laboratory study exposed heart muscle cells grown in dishes to different amounts of nicotine for 48 hours. Nicotine reduced the cells' survival, and the more nicotine and the longer the exposure, the bigger the effect. It also pushed the cells toward programmed cell death. The researchers traced this to nicotine lowering a muscle-specific molecule called miR-133 through a signaling chain (ERK1/2 and SRF), which raised the cell-death enzymes caspase-9 and caspase-3; these results come from cells only, not from animals or people.

Wang L, Li X, Zhou Y et al. (2014). Downregulation of miR-133 via MAPK/ERK signaling pathway involved in nicotine-induced cardiomyocyte apoptosis. Naunyn Schmiedebergs Arch Pharmacol. — PubMed PMID: 24190542 · doi:10.1007/s00210-013-0929-1

Nicotine, cigarette smoking and cardiac arrhythmia: an overview

Review, 2012. This review looks at published studies on how cigarette smoking may cause irregular heart rhythms (arrhythmias), and at what nicotine's role might be. The authors say the cause is probably complex. One possible part is nicotine's effect in promoting scarring (fibrosis) in heart muscle, which may make the heart more sensitive to stress hormones such as adrenaline. They also say other parts of cigarette smoke, such as carbon monoxide and oxidative stress, probably contribute, and that smoking-related coronary artery disease and chronic lung disease may cause arrhythmias on their own.

D'Alessandro A, Boeckelmann I, Hammwhöner M et al. (2012). Nicotine, cigarette smoking and cardiac arrhythmia: an overview. Eur J Prev Cardiol. — PubMed PMID: 22779085 · doi:10.1177/1741826711411738

Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis

Animal study, 2011. Researchers gave adult male mice nicotine injections (2 mg/kg per day) for 10 days. They compared ordinary mice with mice bred to make extra metallothionein in the heart, a protein that soaks up harmful oxygen molecules. In the ordinary mice, nicotine weakened the heart's pumping, slowed how fast heart muscle cells contracted and relaxed, and upset their calcium handling. It also caused a build-up of harmful oxygen molecules, heart-cell death and scarring (fibrosis), while the size of the heart muscle cells did not change. The extra metallothionein lessened these effects. These results come only from mice.

Hu N, Guo R, Han X et al. (2011). Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis. Toxicol Lett. — PubMed PMID: 21238558 · doi:10.1016/j.toxlet.2011.01.007

Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression

Cell study, 2010. Researchers grew heart muscle cells in the lab and exposed them to different amounts of nicotine (0.1 to 100 micromolar). The higher the nicotine dose, the fewer of the cells stayed alive. Nicotine also pushed the cells toward programmed cell death (apoptosis) by causing oxidative stress, and it changed the activity of genes that control cell death: some protective genes such as Bcl-2 were turned down, and others such as P53 and Bax were turned up. The antioxidant glutathione protected the cells by blocking the oxidative stress. These results come from cells in a dish only, not from animals or people.

Zhou X, Sheng Y, Yang R et al. (2010). Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression. Cardiology. — PubMed PMID: 20339300 · doi:10.1159/000301278

Cigarette smoking induces atrial fibrosis in humans via nicotine

Human observational study, 2007. Researchers compared heart tissue from 95 people having heart bypass surgery (46 smokers and 49 non-smokers) to see whether smoking is linked to scarring (fibrosis) in the upper chambers of the heart. In smokers, the amount of smoking over the years was the only factor linked to more scarring, and people who developed an irregular heartbeat (atrial fibrillation) after surgery had more scarring. When heart tissue from 8 non-smokers was exposed to nicotine in the laboratory, a scar-building collagen gene became up to 10 times more active, depending on the nicotine dose. The authors conclude that smoking contributes to this heart scarring through nicotine, and note that such scarring may make irregular heart rhythms more likely.

Goette A, Lendeckel U, Kuchenbecker A et al. (2007). Cigarette smoking induces atrial fibrosis in humans via nicotine. Heart. — PubMed PMID: 17395670 · doi:10.1136/hrt.2005.087171

Nicotine gum-induced atrial fibrillation

Other, 2003. This is a case report of one 39-year-old man with no history of atrial fibrillation (an irregular, often fast heartbeat) who was hospitalized with it after chewing nicotine gum on his own for 7 months. In the week his palpitations began, he was chewing more than one piece per hour at work. Doctors found no other cause, and his heart was shocked back into a normal rhythm. Six months later he had stopped the gum, his heart rhythm was still normal and he had no more palpitations, which the authors say suggests the heavy gum use, and probably a high level of nicotine in his blood, caused the episode.

Choragudi NL, Aronow WS, DeLuca AJ (2003). Nicotine gum-induced atrial fibrillation. Heart Dis. — PubMed PMID: 12713677 · doi:10.1097/01.hdx.0000061700.11321.1a

Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl

Cell study, 2002. Researchers recorded the electrical currents in individual heart muscle cells taken from guinea pigs and exposed them to nicotine at concentrations from 30 microM to 1 mM. Nicotine reduced several of the currents that control the heartbeat's electrical rhythm. At 30 microM it cut one potassium current (IK1) by 43.0% without changing the calcium current. At 100 microM it cut the delayed potassium current by 42.7%, mainly its rapid part (IKr). At 300 microM it reduced the calcium current by 29.3%, and at 1 mM it blocked about 90% of it. The effects were not changed by drugs that block nicotinic receptors, which suggests nicotine acted on the ion channels directly; these results are from animal cells only.

Satoh H (2002). Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl. Vascul Pharmacol. — PubMed PMID: 12616991 · doi:10.1016/s1537-1891(02)00194-5

Direct block of inward rectifier potassium channels by nicotine

Cell study, 2000. Researchers tested whether nicotine directly blocks inward rectifier potassium channels, which help set the resting electrical state of heart cells. They used two cloned human channels, Kir2.1 and Kir2.2, grown in frog egg cells, and the natural version of this current in heart muscle cells from dogs. Nicotine blocked the channels in a dose-dependent way. The block was stronger in the dog heart cells, about 60% at a concentration as low as 0.5 microM, and it was partly reversed when nicotine was washed out. Drugs that block nicotinic, muscarinic and beta-adrenergic receptors did not undo the effect, so nicotine appeared to act on the channels directly. The authors say this may help explain nicotine's effects on the electrical activity of heart cells and may partly contribute to its ability to promote abnormal heart rhythms. These results come from isolated cells only.

Wang H, Yang B, Zhang L et al. (2000). Direct block of inward rectifier potassium channels by nicotine. Toxicol Appl Pharmacol. — PubMed PMID: 10739749 · doi:10.1006/taap.2000.8896

Nicotine depresses the functions of multiple cardiac potassium channels

Cell study, 1999. Researchers tested how nicotine affects potassium channels in heart cells. They used heart muscle cells taken from dogs and frog egg cells engineered to carry human heart potassium channels. Nicotine blocked several types of potassium current that help the heart reset after each beat. Even at a concentration as low as 10 nM, it reduced one of these currents by about 20%. The effect did not depend on nicotinic receptors or on the release of adrenaline-like hormones, so the authors conclude that nicotine acts directly on the channel proteins. They suggest this may help explain how nicotine could trigger heart rhythm problems. These results come from isolated cells only, not from living animals or people.

Wang H, Shi H, Wang Z (1999). Nicotine depresses the functions of multiple cardiac potassium channels. Life Sci. — PubMed PMID: 10503950 · doi:10.1016/s0024-3205(99)00370-7

Additive cardiovascular effects of nicotine and ethanol

Human trial, 1986. Healthy volunteers were given oral ethanol (at two doses) followed by intravenous nicotine to see how alcohol changes nicotine's effects on the heart and blood vessels. Ethanol raised heart rate and blood pressure on its own, and nicotine added to those increases rather than counteracting them; nicotine also narrowed skin blood vessels, but ethanol blunted that particular effect. Ethanol did not change how fast the body broke down nicotine overall, though it modestly increased how quickly nicotine was cleared by the kidneys. The researchers noted these combined heart and blood-vessel effects of alcohol and nicotine together could potentially contribute to abnormal heart rhythms and sudden death in people with existing coronary heart disease.

Benowitz NL, Jones RT, Jacob P (1986). Additive cardiovascular effects of nicotine and ethanol. Clin Pharmacol Ther. — PubMed PMID: 3757405 · doi:10.1038/clpt.1986.200

A study of the effects of nicotine in the intact dog and the propensity for arrhythmias

Animal study, 1979. This 1979 study tested nicotine's effects on heart rhythm in intact dogs. After nicotine exposure, the refractory periods (how long heart tissue needs to recover between beats) became longer, and the diastolic current threshold rose in every animal. In four dogs the threshold for repetitive firing dropped, and those same four had prolonged relative refractory periods. The researchers concluded that nicotine may increase the risk of abnormal heart rhythms (arrhythmias) when a well-timed, strong-enough extra heartbeat hits a ventricle where recovery times vary enough to sustain a re-entrant arrhythmia.

Flowers NC, Hand RC, Sohi GS et al. (1979). A study of the effects of nicotine in the intact dog and the propensity for arrhythmias. J Environ Pathol Toxicol. — PubMed PMID: 44719

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PubMed Topic Searches

1. PubMed: Heart Rhythm and Myocarditis and nicotine (the search this page is built from)

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Connections

• The Heart’s Electrical System & the ECG — interactive animation
• Nicotine: The Research
• Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery

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