Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury

Abstract

Background. Severe burn trauma leads to an immediate and strong inflammatory response inciting cardiac dysfunction that is associated with high morbidity and mortality. The aim of this study was to determine whether transdermal application of nicotine could influence the burn-induced cardiac dysfunction via its known immunomodulatory effects. Material and Methods. A standardized rat burn model was used in 35 male Sprague Dawley rats. The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham group with five experimental animals per group. The latter two groups received nicotine administration. Using microtip catheterization, functional parameters of the heart were assessed 12 or 24 hours after infliction of burn trauma. Results. Burn trauma led to significantly decreased blood pressure (BP) values whereas nicotine administration normalized BP. As expected, burn trauma also induced a significant deterioration of myocardial contractility and relaxation parameters. After application of nicotine these adverse effects were attenuated. Conclusion. The present study showed that transdermal nicotine administration has normalizing effects on burn-induced myocardial dysfunction parameters. Further research is warranted to gain insight in molecular mechanisms and pathways and to evaluate potential treatment options in humans.

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“… 19 In their study, Van Maanen et al 20 showed that intraperitoneally nicotine application to mice could alleviate clinical rheumatoid arthritis. In addition, Leib et al 21 showed that nicotine reduces inflammation in a mouse model of autoimmune Myocarditis and Claassen et al 35 , 36 verified an antiinflammatory effect of Nicotine after burn trauma. In clinical studies, the anti-inflammatory effect of nicotine has been verified in patients suffering from ulcerative colitis.…”

Cholinergic modulation of the immune system presents new approaches for treating inflammation

“…Beneficial effects of VNS were mediated by nicotinic receptors since they were blocked by hexamethonium but unaffected by atropine. Consistent with nicotinic receptor mediation of responses to VNS, transdermal administration of nicotine to rats at the time of burn injury attenuated or inhibited elevation of tissue pro-inflammatory cytokine levels, normalized blood pressure, and improved myocardial contractile function (Claassen et al, 2014; Claassen et al, 2015). While these were primarily acute studies, other investigators have demonstrated that treatment with GTS-21 increases 7-day survival in burned mice to 100% as compared to 25% in saline treated mice (Khan et al., 2012).…”

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“…Transdermal nicotine has already been found to be highly effective in attenuating life-threatening cardiac dysfunction triggered by severe burns. 8 Therapeutic benefits were associated with anti-inflammatory and immunomodulating effects of nicotine in this study. 8 Nicotine has been demonstrated to interact with a target—the α7 nicotinic acetylcholine receptor (α7nAChR)—for attenuation of proinflammatory cytokine release.…”