Journal
CIRCULATION
Volume 120, Issue 11, Pages S1-S9Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.108.843938
Keywords
apoptosis; capsaicin; infarction; nervous system; remote preconditioning; signal transduction; sympathetic
Funding
- NHLBI NIH HHS [HL63034, R01 HL063034, HL-087861, HL62984, R01 HL091478-02, HL091478, R01 HL063034-09, R01 HL087861-02, R01 HL087861-03, R01 HL087861-03S1, HL076684, R01 HL076684, P01 HL062984, R01 HL087861, R01 HL087861-01, R01 HL091478] Funding Source: Medline
- NINDS NIH HHS [NS55860, R01 NS045594, R01 NS055860, NS45594] Funding Source: Medline
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Background-Although remote ischemic stimuli have been shown to elicit cardioprotection against ischemia/reperfusion injury, there is little known about the effects of nonischemic stimuli. We previously described a remote cardioprotective effect of nonischemic surgical trauma (abdominal incision) called remote preconditioning of trauma (RPCT). In the present study, we elucidate mechanisms underlying this phenomenon. Methods and Results-We used a murine model of myocardial infarction to evaluate ischemia/reperfusion injury, and either abdominal surgical incision, or application of topical capsaicin, to elicit cardioprotection. We show that the cardioprotective effect of RPCT is initiated by skin nociception, and requires neurogenic signaling involving spinal nerves and activation of cardiac sensory and sympathetic nerves. Our results demonstrate bradykinin-dependent activation and repression, respectively, of PKC epsilon and PKC delta in myocardium after RPCT, and we show involvement of the K-ATP channels in cardioprotection. Finally, we show that topical application of capsaicin, which selectively activates C sensory fibers in the skin, mimics the cardioprotective effect of RPCT against myocardial infarction. Conclusions-Nontraumatic nociceptive preconditioning represents a novel therapeutic strategy for cardioprotection with great potential clinical utility. (Circulation. 2009;120[suppl 1]:S1-S9.)
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