Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors

Kathrine L. Redington, Tara Disenhouse, Samuel C. Strantzas, Rachel Gladstone, Can Wei, Michael B. Tropak, Xiaojing Dai, Cedric Manlhiot, Jing Li

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


We have previously shown that remote ischemic preconditioning by limb ischemia (rIPC) or intra-arterial adenosine releases a dialyzable cardioprotective circulating factor(s), the release of which requires an intact neural connection to the limb and is blocked by pretreatment with S-nitroso-N-acetylpenicillamine (SNAP). Remote cardioprotection can be induced by other forms of peripheral stimulation including topical capsaicin, but the mechanisms of their signal transduction are incompletely understood. Rabbits were anesthetized by intravenous pentobarbital, intubated and ventilated, then randomized (4-7 animals in each group) to receive sham procedure, rIPC (4 cycles of 5 min lower limb ischemia, 5 min reperfusion), direct femoral nerve stimulation, topical capsaicin, pretreatment with intra-arterial SNAP + capsaicin, pretreatment with topical DMSO (a sensory nerve blocker) + topical capsaicin, or pretreatment with intra-arterial SNAP + femoral nerve stimulation, topical DMSO alone, or intra-arterial SNAP alone. Blood was then rapidly drawn from the carotid artery to produce the plasma dialysate which was used to perfuse a naive heart from an untreated donor rabbit. The infarct size and recovery of LV-developed pressure and end-diastolic pressure were measured after 30 min of global ischemia and 120 min of reperfusion. Compared to sham, dialysate from rIPC, femoral nerve stimulation, and topical capsaicin groups all produced significant cardioprotection with significantly reduced infarct size, and improved the postischemic cardiac performance. Cardioprotection was not seen in the topical DMSO-capsaicin, SNAP + capsaicin, and SNAP + FNS groups. These results confirm the central role of peripheral nerves in the local signal transduction of remote cardioprotection. Direct electrical or peripheral neural stimulation evokes the release of cardioprotective substances into the bloodstream, with comparable effects to that of rIPC induced by limb ischemia.

Original languageEnglish (US)
Article number0241
JournalBasic Research in Cardiology
Issue number2
StatePublished - Mar 2012
Externally publishedYes


  • Capsaicin
  • Ischemia
  • Ischemic preconditioning
  • Nerve stimulation
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors'. Together they form a unique fingerprint.

Cite this