TY - JOUR
T1 - Transcutaneous electrical nerve stimulation as a novel method of remote preconditioning
T2 - In vitro validation in an animal model and first human observations
AU - Merlocco, Anthony C.
AU - Redington, Kathrine L.
AU - Disenhouse, Tara
AU - Strantzas, Samuel C.
AU - Gladstone, Rachel
AU - Wei, Can
AU - Tropak, Michael B.
AU - Manlhiot, Cedric
AU - Li, Jing
AU - Redington, Andrew N.
N1 - Funding Information:
This study was supported by grants from the Leducq Foundation and Canadian Institutes of Health Research.
PY - 2014/5
Y1 - 2014/5
N2 - Remote ischemic preconditioning (rIPC) induced by transient limb ischemia (li-rIPC) leads to neurally dependent release of blood-borne factors that provide potent cardioprotection. We hypothesized that transcutaneous electrical nerve stimulation (TENS) is a clinically relevant stimulus of rIPC. Study 1: seven rabbits were subjected to lower limb TENS; six to li-rIPC, and six to sham intervention. Blood was drawn and used to prepare a dialysate for subsequent analysis of cardioprotection in rabbit Langendorff preparation. Study 2: 14 healthy adults underwent upper limb TENS stimulation on one study day, 10 of whom also underwent li-rIPC on another study day. Blood was drawn before and after each stimulus, dialysate prepared, and cardioprotective activity assessed in mouse Langendorff preparation. The infarct size and myocardial recovery were measured after 30 min of global ischemia and 60 or 120 min of reperfusion. Animal validation: compared to control, TENS induced marked cardioprotection with significantly reduced infarct size (TENS vs. sham p\0.01, rIPC vs. sham p\0.01, TENS vs. rIPC p = ns) and improved functional recovery during reperfusion. Human study: compared to baseline, dialysate after rIPC (pre-rIPC vs. post-rIPC, p\0.001) and TENS provided potent cardioprotection (pre-TENS vs. post-TENS p\0.001) and improved myocardial recovery during reperfusion. The cardioprotective effects of TENS dialysates were blocked by pretreatment of the receptor heart with the opioid antagonist naloxone. TENS is a novel method for inducing cardioprotection and may provide an alternative to the limb ischemia stimulus for induction of rIPC clinically.
AB - Remote ischemic preconditioning (rIPC) induced by transient limb ischemia (li-rIPC) leads to neurally dependent release of blood-borne factors that provide potent cardioprotection. We hypothesized that transcutaneous electrical nerve stimulation (TENS) is a clinically relevant stimulus of rIPC. Study 1: seven rabbits were subjected to lower limb TENS; six to li-rIPC, and six to sham intervention. Blood was drawn and used to prepare a dialysate for subsequent analysis of cardioprotection in rabbit Langendorff preparation. Study 2: 14 healthy adults underwent upper limb TENS stimulation on one study day, 10 of whom also underwent li-rIPC on another study day. Blood was drawn before and after each stimulus, dialysate prepared, and cardioprotective activity assessed in mouse Langendorff preparation. The infarct size and myocardial recovery were measured after 30 min of global ischemia and 60 or 120 min of reperfusion. Animal validation: compared to control, TENS induced marked cardioprotection with significantly reduced infarct size (TENS vs. sham p\0.01, rIPC vs. sham p\0.01, TENS vs. rIPC p = ns) and improved functional recovery during reperfusion. Human study: compared to baseline, dialysate after rIPC (pre-rIPC vs. post-rIPC, p\0.001) and TENS provided potent cardioprotection (pre-TENS vs. post-TENS p\0.001) and improved myocardial recovery during reperfusion. The cardioprotective effects of TENS dialysates were blocked by pretreatment of the receptor heart with the opioid antagonist naloxone. TENS is a novel method for inducing cardioprotection and may provide an alternative to the limb ischemia stimulus for induction of rIPC clinically.
KW - Ischemia
KW - Ischemic preconditioning
KW - Reperfusion
KW - Transcutaneous electrical nerve stimulation
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U2 - 10.1007/s00395-014-0406-0
DO - 10.1007/s00395-014-0406-0
M3 - Article
C2 - 24604614
AN - SCOPUS:84894871419
SN - 0300-8428
VL - 109
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
IS - 3
M1 - 406
ER -