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


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 PKCepsilon and PKCdelta 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.
Jones
W Keith
WK
Department of Pharmacology and Cell Biophysics, University of Cincinnati, OH 45267-0575, USA.
Fan
Guo-Chang
GC
Liao
Siyun
S
Zhang
Jun-Ming
JM
Wang
Yang
Y
Weintraub
Neal L
NL
Kranias
Evangelia G
EG
Schultz
Jo El
JE
Lorenz
John
J
Ren
Xiaoping
X
D000818:Animals; D017209:Apoptosis; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000294:innervation*; D019194:Ischemic Preconditioning / Q000379:methods*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010146:Pain / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D054086:KATP Channels; D011493:Protein Kinase C; D002211:Capsaicin