Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling

W. Keith Jones, Guo Chang Fan, Siyun Liao, Jun Ming Zhang, Yang Wang, Neal Lee Weintraub, Evangelia G. Kranias, Jo El Schultz, John Lorenz, Xiaoping Ren

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

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 PKCεe and PKCδ in myocardium after RPCT, and we show involvement of the KATP 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.)

Original languageEnglish (US)
Pages (from-to)S1-S9
JournalCirculation
Volume120
Issue numberSUPPL. 1
DOIs
StatePublished - 2009

Keywords

  • Apoptosis
  • Capsaicin
  • Infarction
  • Nervous system
  • Remote preconditioning
  • Signal transduction
  • Sympathetic

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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