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IcyHot analgesic topical cream limits cardiac injury in rodents.
Transl Res. 2020 Jul 03 [Online ahead of print]TR

Abstract

Little is known whether topical analgesic creams, whose natural products enter the blood stream after application, affect myocardial infarct size. Here we tested whether topical analgesic creams can trigger remote cardioprotection and the mechanism involved. Male Sprague Dawley rats were used for an in vivo rodent model consisting of 30 minutes left anterior descending coronary artery ischemia and 2 hours of reperfusion followed by infarct size assessment. The topical analgesic IcyHot, applied to the abdomen prior to ischemia, reduced myocardial infarct size versus control (41 ± 3* vs 62 ± 1, n= 6/group, *P < 0.001). In contrast, the topical analgesic creams Preparation H, Aspercreme Heat, or Tiger Balm did not alter infarct size. IcyHot, unlike Preparation H, increased circulating methyl salicylate levels during reperfusion (3.0 ± 0.6 vs 0.4 ± 0.2 mg/dL, n = 6, *P < 0.001, measured at the internal jugular vein). Methyl salicylate (10 μM) applied to isolated adult cardiac myocytes during reoxygenation reduced cell death when compared to vehicle (21% ± 2%* vs 30% ± 2% of trypan blue positive cells, n = 9/group, *P < 0.01). Further, treatment with the TRP ankyrin 1 (TRPA1) inhibitors TCS-5861528 (1 μM) or AP-18 (1 μM) blocked the methyl salicylate-induced protective effect in isolated adult cardiomyocytes. In intact rodents, either of the TRPA1 inhibitors (1 mg/kg, intravenous) given prior to IcyHot topical application blocked IcyHot-induced infarct size reduction. IcyHot also reduced infarct size when applied 24 hours prior to myocardial ischemia or during myocardial ischemia versus control. Together, these findings support IcyHot analgesic cream can trigger remote cardioprotection through releasing methyl salicylate into the bloodstream with cardioprotection occurring by a TRPA1-dependent mechanism.

Authors+Show Affiliations

Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California. Electronic address: ergross@stanford.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32629175

Citation

Wu, Yun, et al. "IcyHot Analgesic Topical Cream Limits Cardiac Injury in Rodents." Translational Research : the Journal of Laboratory and Clinical Medicine, 2020.
Wu Y, Chen AW, Goodnough CL, et al. IcyHot analgesic topical cream limits cardiac injury in rodents. Transl Res. 2020.
Wu, Y., Chen, A. W., Goodnough, C. L., Lu, Y., Zhang, Y., & Gross, E. R. (2020). IcyHot analgesic topical cream limits cardiac injury in rodents. Translational Research : the Journal of Laboratory and Clinical Medicine. https://doi.org/10.1016/j.trsl.2020.06.009
Wu Y, et al. IcyHot Analgesic Topical Cream Limits Cardiac Injury in Rodents. Transl Res. 2020 Jul 3; PubMed PMID: 32629175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IcyHot analgesic topical cream limits cardiac injury in rodents. AU - Wu,Yun, AU - Chen,Annabel W, AU - Goodnough,Candida L, AU - Lu,Yao, AU - Zhang,Ye, AU - Gross,Eric R, Y1 - 2020/07/03/ PY - 2020/01/09/received PY - 2020/05/15/revised PY - 2020/06/17/accepted PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez JF - Translational research : the journal of laboratory and clinical medicine JO - Transl Res N2 - Little is known whether topical analgesic creams, whose natural products enter the blood stream after application, affect myocardial infarct size. Here we tested whether topical analgesic creams can trigger remote cardioprotection and the mechanism involved. Male Sprague Dawley rats were used for an in vivo rodent model consisting of 30 minutes left anterior descending coronary artery ischemia and 2 hours of reperfusion followed by infarct size assessment. The topical analgesic IcyHot, applied to the abdomen prior to ischemia, reduced myocardial infarct size versus control (41 ± 3* vs 62 ± 1, n= 6/group, *P < 0.001). In contrast, the topical analgesic creams Preparation H, Aspercreme Heat, or Tiger Balm did not alter infarct size. IcyHot, unlike Preparation H, increased circulating methyl salicylate levels during reperfusion (3.0 ± 0.6 vs 0.4 ± 0.2 mg/dL, n = 6, *P < 0.001, measured at the internal jugular vein). Methyl salicylate (10 μM) applied to isolated adult cardiac myocytes during reoxygenation reduced cell death when compared to vehicle (21% ± 2%* vs 30% ± 2% of trypan blue positive cells, n = 9/group, *P < 0.01). Further, treatment with the TRP ankyrin 1 (TRPA1) inhibitors TCS-5861528 (1 μM) or AP-18 (1 μM) blocked the methyl salicylate-induced protective effect in isolated adult cardiomyocytes. In intact rodents, either of the TRPA1 inhibitors (1 mg/kg, intravenous) given prior to IcyHot topical application blocked IcyHot-induced infarct size reduction. IcyHot also reduced infarct size when applied 24 hours prior to myocardial ischemia or during myocardial ischemia versus control. Together, these findings support IcyHot analgesic cream can trigger remote cardioprotection through releasing methyl salicylate into the bloodstream with cardioprotection occurring by a TRPA1-dependent mechanism. SN - 1878-1810 UR - https://www.unboundmedicine.com/medline/citation/32629175/IcyHot_analgesic_topical_cream_limits_cardiac_injury_in_rodents L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-5244(20)30148-1 DB - PRIME DP - Unbound Medicine ER -
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