Abstract
Purpose
Topical capsaicin application was shown to reduce infarct size in experimental animal models. We hypothesized that cardioprotective properties of topical capsaicin application could be related to its hypothermic effect.
Methods
In the first arm of the study, anesthetized rats received capsaicin cream (Caps group) or vehicle (Control group, Ctrl) applied either 15 or 30 min prior to a 30-min coronary artery occlusion followed by 2-h reperfusion. Core body temperature was allowed to run its course, and was monitored via rectal probe. At the end of the protocol, hearts were excised and risk zone and infarct size were measured. In an additional set of animals, hearts were excised immediately after a 15-min application of capsaicin/vehicle, and were used to measure phosphorylated Akt and Erk1/2 with western blots. In the second arm of the study Ctrl (n = 6) and Caps-treated (n = 5) animals were subjected to the same protocol as rats in the first arm, but core body temperature was maintained at 36 °C.
Results
In the first arm of the study, capsaicin produced a rapid decrease in rectal temperature ranging from 0.22 to 1.78 °C at pre-occlusion, with a median level of 0.97 °C. A capsaicin-induced temperature decrease of >0.97 °C was associated with a 31.2 % smaller infarct compared to the control group. Capsaicin treatment induced an increase in the levels of phosphorylated Akt and Erk1/2 at the end of capsaicin cream application. No increase in the phosphorylation of downstream p70S6 was observed. Levels of phosphorylated Akt- and Erk1/2 did not correlate with temperature changes after treatment. In the second arm of the study, in which body core temperature was maintained at 36 °C, no change in the infarct size was observed in the capsaicin vs. control group.
Conclusion
In the current study we for the first time demonstrated that the capsaicin induced cardioprotective effect might be related to mild hypothermia, caused by capsaicin topical application. The salvage kinase pathway appears not to be critical for capsaicin-induced cardioprotection.
Similar content being viewed by others
References
Hale SL, Kloner RA. Mild hypothermia as a cardioprotective approach for acute myocardial infarction: laboratory to clinical approach. J Cardiovasc Pharmacol Ther. 2011;16:131–9.
Tissier R, Ghaleb B, Cohen MV, Downey JM, Berdeaux A. Myocardial protection with mild hypothermia. Cardiovasc Res. 2012;94:217–25.
Swanson DM, Dubin AE, Shah C, et al. Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist. J Med Chem. 2005;48:1857–72.
Jakab B, Heyles Z, Varga A, et al. Pharmacological characterization of the TRPV1 receptor antagonist JYL1421 (SC0030) in vivo and in vitro in the rat. Eur J Pharmacol. 2005;517:35–44.
Jones WK, Fan GC, Liao S, et al. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation. 2009;120 suppl 1:S1–9.
Gross GJ, Hsu A, Gross ER, Falck JR, Nithipatikom K. Factors mediating remote preconditioning of trauma in the rat heart: central role of the cytochrome P450 epoxygenase pathway in mediating infarct size reduction. J Cardiovasc Pharmacol Ther. 2013;18:38–45.
Yang X, Liu Y, Yang XM, et al. Cardioprotection by mild hypothermia during ischemia involves preservation of ERK activity. Basic Res Cardiol. 2011;106:421–30.
National Research Council. Guide for the care and use of laboratory animals, 8th ed. Washington, DC: The National Academies Press; 2011.
Dow J, Bhandari A, Simkhovich BZ, Hale SL, Kloner RA. The effect of acute versus delayed remote ischemic preconditioning on reperfusion induced ventricular arrhythmias. J Cardiovasc Electrophysiol. 2012;23:1374–83.
Gross ER, Hsu AK, Gross GJ, Mochly-Rosen D. Acute capsaicin treatment reduces myocardial infarct size in rats via the transient receptor potential vanilloid 1 channel. J Crit Care. 2010;25:E18.
Duncker DJ, Klassen CL, Ishibashi Y, Herrlinger SH, Pavek TJ, Bache RJ. Effect of temperature on myocardial infarction in swine. Am J Physiol. 1996;270:H1189–99.
Chien GL, Wolff RA, Davis RF, Van Winkle D. Normothermic range temperature affects myocardial infarct size. Cardiovasc Res. 1994;28:1014–7.
Hale SL, Kloner RA. Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia. Am J Physiol 1977;273:H220–7.
Jancso-Gabor A, Szolcsanyi J, Jancso N. Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J Physiol. 1970;206:495–507.
Simkhovich BZ, Hale SL, Kloner RA. Metabolic mechanism by which mild regional hypothermia preserves ischemic tissue. J Cardiovasc Pharmacol Ther. 2004;9:83–90.
Shao ZH, Sharp WW, Wojcik KR, et al. Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants. Am J Physiol. 2010;298:H2164–73.
Mochizuki T, Yu S, Katoh T, Aoki K, Sato S. Cardioprotective effect of therapeutic hypothermia at 34 °C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model. Resuscitation. 2012;83:238–42.
Acknowledgments
This study was supported by a generous grant from the Los Angeles Thoracic and Cardiovascular Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dow, J., Simkhovich, B.Z., Hale, S.L. et al. Capsaicin-Induced Cardioprotection. Is Hypothermia or the Salvage Kinase Pathway Involved?. Cardiovasc Drugs Ther 28, 295–301 (2014). https://doi.org/10.1007/s10557-014-6527-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10557-014-6527-8