Nicotine, Heart Rhythm and Myocarditis: The Research

Nicotine acts on the heart through adrenaline and directly on cardiac ion channels, and the alpha-7 anti-inflammatory pathway has been studied in heart-muscle inflammation. This page collects the published research on nicotine, heart rhythm and myocarditis, each paper summarised in plain language with its PubMed record.

This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.

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The Papers (23)

Newest first. Study types on this page — Human trial: 2 · Review: 4 · Animal study: 10 · Cell study: 7. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels

Cell study, 2022. Researchers tested five different concentrations of nicotine on three types of healthy cells grown in the lab: skin cells, heart muscle cells and liver cells. They also tested it on the membrane of fertilised hen's eggs, a lab method used to check whether a substance irritates blood vessels. In all three cell types, nicotine strongly reduced cell survival, with fewer than 2% of cells still alive at the highest concentration tested. The cells also changed shape, their nuclei showed signs of programmed cell death, and nicotine strongly irritated the egg membrane's blood vessels. These results come only from lab-grown cells and egg membranes, not from people.

Chioran D, Sitaru A, Macasoi I et al. (2022). Nicotine Exerts Cytotoxic Effects in a Panel of Healthy Cell Lines and Strong Irritating Potential on Blood Vessels. Int J Environ Res Public Health. — PubMed PMID: 35886732 · doi:10.3390/ijerph19148881

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

Nicotine supplementation enhances simulated game performance of archery athletes

Human trial, 2021. Eleven college archers each took 2 mg of nicotine gum on one occasion and a placebo on another, in a randomized crossover trial. Thirty minutes after the nicotine gum, they were faster on a 'correct rejection' attention task (7.29 vs 8.23 msec) and on a pegboard dexterity test (48.76 vs 53.41 seconds), but their motor reaction times did not change. Nicotine lowered heart rate variability and changed a saliva enzyme linked to the stress response, and the archery score was higher with nicotine than with placebo (the abstract reports 298.05 and 290.58 points for the two conditions). The authors conclude that nicotine improved the archers' performance by sharpening cognitive function and stimulating the body's adrenaline-driven stress system.

Hung BL, Chen LJ, Chen YY et al. (2021). Nicotine supplementation enhances simulated game performance of archery athletes. J Int Soc Sports Nutr. — PubMed PMID: 33602279 · doi:10.1186/s12970-021-00413-9

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

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Cell study, 2020. Researchers tested how nicotine affects heart muscle cells taken from newborn rats, grown in the lab. Nicotine made the cells grow abnormally large, a change linked to heart thickening, and disrupted autophagy, the cell's recycling system. It did this by lowering the activity of an enzyme called cathepsin B and raising levels of reactive oxygen species, which switched on two stress pathways known as p38MAPK and JNK. A drug used for poor circulation in the legs, cilostazol, reversed these effects in the cells, as did an antioxidant and blockers of the two stress pathways. These results come only from rat cells in the lab.

Wang SY, Ni X, Hu KQ et al. (2020). Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop. Int J Biol Sci. — PubMed PMID: 32398966 · doi:10.7150/ijbs.43825

Adverse effects of nicotine on cardiogenic differentiation from human embryonic stem cells detected by single-cell RNA sequencing

Cell study, 2020. Researchers exposed human embryonic stem cells in the lab to nicotine while coaxing them to turn into heart cells, and used single-cell genetic analysis to see which cell types and genes were affected. Nicotine at 0.1 to 10 micromolar did not change how fast the stem cells multiplied, but at 1 micromolar it reduced the numbers of early heart-forming cells and related cell types and switched down genes that guide heart development, leading to a significant drop in a marker of mature heart muscle cells. The authors conclude that nicotine may directly harm early heart development, though this was shown only in cells in a dish, not in people or animals.

He B, Chen J, Tian M et al. (2020). Adverse effects of nicotine on cardiogenic differentiation from human embryonic stem cells detected by single-cell RNA sequencing. Biochem Biophys Res Commun. — PubMed PMID: 32276728 · doi:10.1016/j.bbrc.2020.03.149

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

Electronic cigarettes and cardiovascular health: what do we know so far?

Review, 2019. This review looks at what is known about how e-cigarettes affect the heart and blood vessels. The authors note that nicotine is the main biologically active substance in e-cigarette vapor, while the cancer-causing chemicals and burning by-products found in tobacco smoke are very low or undetectable. They describe how tobacco cigarettes harm the heart through inflammation, oxidative damage, clogged arteries, blood clots and nervous-system activation, and they discuss which of these ways of causing harm may also apply to e-cigarette use. They conclude that although e-cigarettes are generally thought to be safer than tobacco cigarettes, their overall effects on heart health are still uncertain, and they discuss the debate between rising e-cigarette use among young people and the use of e-cigarettes to help people quit smoking.

MacDonald A, Middlekauff HR (2019). Electronic cigarettes and cardiovascular health: what do we know so far?. Vasc Health Risk Manag. — PubMed PMID: 31417268 · doi:10.2147/VHRM.S175970

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

Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development

Cell study, 2019. Researchers grew human embryonic stem cells into early embryo-like cell clusters in the laboratory, with and without nicotine, and used single-cell genetic sequencing to see how each type of cell responded. Nicotine changed how different developing cell lines behaved and disrupted signaling between cells. It also lowered cell survival, raised levels of damaging reactive oxygen molecules, changed the cell cycle, and caused abnormal calcium signaling in muscle cells, which the researchers confirmed in stem-cell-derived heart muscle cells. These results come only from cells in a dish, and the authors say they point to direct harmful effects of nicotine on early human embryonic development.

Guo H, Tian L, Zhang JZ et al. (2019). Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development. Stem Cell Reports. — PubMed PMID: 30827876 · doi:10.1016/j.stemcr.2019.01.022

Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats

Animal study, 2017. This study in pregnant rats tested whether breathing in nicotine, delivered as an aerosol designed to reach the lungs and produce blood nicotine levels like those of a human smoker, harms the heart and blood flow to the womb. Inhaled nicotine briefly reduced blood flow in the uterine artery and made it irregular, caused large irregular swings in blood pressure, and triggered several kinds of irregular heartbeat, including heart block. These effects were prevented by a drug that blocks nicotinic receptors, and cutting the ovarian nerve that supplies the womb's blood vessels prevented the drop in uterine blood flow. The authors suggest this may help explain smoking-related pregnancy complications and say the findings challenge the safety of inhaling pure nicotine, as with e-cigarettes; these results are in rats only.

Shao XM, López-Valdés HE, Liang J et al. (2017). Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats. Sci Rep. — PubMed PMID: 29209071 · doi:10.1038/s41598-017-17301-5

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 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

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

E-cigarettes and cardiovascular risk: beyond science and mysticism

Review, 2014. This review looks at what is known about e-cigarettes, which deliver nicotine, and the risk to the heart and blood vessels. The authors say e-cigarettes seem less hazardous than regular cigarettes. However, studies show that users can inhale several potentially harmful substances during repeated puffing, especially nicotine, ultrafine particles and volatile organic compounds, and these can also be released in exhaled air. The authors say this could raise the risk of irregular heart rhythms and high blood pressure, which may increase some users' risk of heart events. They also note reported poisonings from absorbing large amounts of nicotine, and they call for more research to establish whether these devices are safe for the heart.

Lippi G, Favaloro EJ, Meschi T et al. (2014). E-cigarettes and cardiovascular risk: beyond science and mysticism. Semin Thromb Hemost. — PubMed PMID: 24343348 · doi:10.1055/s-0033-1363468

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

Prenatal nicotine exposure alters postnatal cardiorespiratory integration in young male but not female rats

Animal study, 2011. Researchers gave pregnant rats either nicotine (6 mg/kg/day) or salt water and then measured heart rate and breathing in the offspring at three young ages (postnatal days 13, 16 and 26). Male pups exposed to nicotine before birth showed a trend toward a higher resting heart rate, an altered heart-rate response to low oxygen (blunted at day 13 and raised at day 26), and reduced respiratory sinus arrhythmia (the normal rise and fall of heart rate with breathing) at day 26; breathing rate itself was not affected. No significant effects were found in female offspring at any age. The authors suggest these changes in males may persist and could raise the risk of conditions such as high blood pressure later in life, though this was shown only in rats.

Boychuk CR, Hayward LF (2011). Prenatal nicotine exposure alters postnatal cardiorespiratory integration in young male but not female rats. Exp Neurol. — PubMed PMID: 21945005 · doi:10.1016/j.expneurol.2011.09.006

Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis

Animal study, 2011. Researchers caused an autoimmune inflammation of the heart muscle (myocarditis) in mice and then gave some of the mice nicotine in their drinking water at two concentrations, for either 3 days or 21 days. The untreated mice developed extensive heart inflammation and scarring, with high levels of the inflammatory signals interleukin-6 and tumor necrosis factor-alpha. In the mice given nicotine, there was less inflammation in the heart muscle, lower levels of these inflammatory signals and related chemokines, and less of several proteins linked to heart failure. Another drug that raises the body's own acetylcholine (neostigmine) did not change the disease, and these results come from mice only, not people.

Leib C, Göser S, Lüthje D et al. (2011). Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis. Circ Res. — PubMed PMID: 21597011 · doi:10.1161/CIRCRESAHA.111.245563

Fetal and offspring arrhythmia following exposure to nicotine during pregnancy

Animal study, 2010. Researchers gave nicotine to pregnant sheep and pregnant rats to see whether it affects the heart rhythm of the unborn young and of the offspring later in life. In fetal sheep, nicotine given to the mother changed the fetal heart rate and caused irregular heartbeats, including single and multiple skipped beats, and lowered the oxygen level in the fetal blood, while other blood measures such as pH, lactic acid and salt levels did not change. In rat offspring 4-5 months after birth, those exposed to nicotine before birth had a faster heart rate and more premature ventricular contractions (extra heartbeats) under restraint stress, and more arrhythmias when given nicotine. These results come from animals only; the authors conclude that nicotine exposure in pregnancy can cause fetal arrhythmia, possibly through low oxygen in the womb, and raises the risk of arrhythmia in adult offspring.

Feng Y, Caiping M, Li C et al. (2010). Fetal and offspring arrhythmia following exposure to nicotine during pregnancy. J Appl Toxicol. — PubMed PMID: 19728315 · doi:10.1002/jat.1471

Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts

Animal study, 2003. Researchers studied hearts from normal mice and from mice that lack the Kcnq1 gene, which helps the heart reset between beats. They tested the hearts outside the body. At rest the two groups had the same heart rhythm readings. When nicotine was added, the hearts lacking the gene took clearly longer to recover after each beat, a pattern called long QT (corrected QT of 92 ms compared with 66 ms in normal hearts). The stress hormones epinephrine and isoproterenol had the same effect, and in live mice the stress of handling and injection raised corrected QT by 11% in the gene-lacking mice versus -1% in normal mice, so the authors conclude that stimulation of the body's fight-or-flight nerves brings out the long QT pattern in these mice. These results come from mice only.

Tosaka T, Casimiro MC, Rong Q et al. (2003). Nicotine induces a long QT phenotype in Kcnq1-deficient mouse hearts. J Pharmacol Exp Ther. — PubMed PMID: 12766260 · doi:10.1124/jpet.103.053017

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

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