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 journalArticle

Abstract

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
Volume107
Issue number2
DOIs
StatePublished - Jan 9 2012
Externally publishedYes

Fingerprint

S-Nitroso-N-Acetylpenicillamine
Capsaicin
Peripheral Nerves
Femoral Nerve
Ischemia
Dimethyl Sulfoxide
Extremities
Dialysis Solutions
Reperfusion
Signal Transduction
Rabbits
Ischemic Preconditioning
Pentobarbital
Carotid Arteries
Adenosine
Lower Extremity
Blood Pressure
Pressure

Keywords

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

ASJC Scopus subject areas

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

Cite this

Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors. / Redington, Kathrine L.; Disenhouse, Tara; Strantzas, Samuel C.; Gladstone, Rachel; Wei, Can; Tropak, Michael B.; Dai, Xiaojing; Manlhiot, Cedric; Li, Jing.

In: Basic Research in Cardiology, Vol. 107, No. 2, 0241, 09.01.2012.

Research output: Contribution to journalArticle

Redington, Kathrine L. ; Disenhouse, Tara ; Strantzas, Samuel C. ; Gladstone, Rachel ; Wei, Can ; Tropak, Michael B. ; Dai, Xiaojing ; Manlhiot, Cedric ; Li, Jing. / Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors. In: Basic Research in Cardiology. 2012 ; Vol. 107, No. 2.
@article{bcc10b7feeb646b4b55c2a85b0b7b311,
title = "Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors",
abstract = "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.",
keywords = "Capsaicin, Ischemia, Ischemic preconditioning, Nerve stimulation, Reperfusion",
author = "Redington, {Kathrine L.} and Tara Disenhouse and Strantzas, {Samuel C.} and Rachel Gladstone and Can Wei and Tropak, {Michael B.} and Xiaojing Dai and Cedric Manlhiot and Jing Li",
year = "2012",
month = "1",
day = "9",
doi = "10.1007/s00395-011-0241-5",
language = "English (US)",
volume = "107",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "2",

}

TY - JOUR

T1 - Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors

AU - Redington, Kathrine L.

AU - Disenhouse, Tara

AU - Strantzas, Samuel C.

AU - Gladstone, Rachel

AU - Wei, Can

AU - Tropak, Michael B.

AU - Dai, Xiaojing

AU - Manlhiot, Cedric

AU - Li, Jing

PY - 2012/1/9

Y1 - 2012/1/9

N2 - 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.

AB - 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.

KW - Capsaicin

KW - Ischemia

KW - Ischemic preconditioning

KW - Nerve stimulation

KW - Reperfusion

UR - http://www.scopus.com/inward/record.url?scp=84859734215&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859734215&partnerID=8YFLogxK

U2 - 10.1007/s00395-011-0241-5

DO - 10.1007/s00395-011-0241-5

M3 - Article

C2 - 22231674

AN - SCOPUS:84859734215

VL - 107

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 2

M1 - 0241

ER -