Capsaicin-Induced Cardioprotection. Is Hypothermia or the Salvage Kinase Pathway Involved?

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.