TY - JOUR
T1 - Intravenous electrical vagal nerve stimulation prior to coronary reperfusion in a canine ischemia-reperfusion model markedly reduces infarct size and prevents subsequent heart failure
AU - Arimura, Takahiro
AU - Saku, Keita
AU - Kakino, Takamori
AU - Nishikawa, Takuya
AU - Tohyama, Takeshi
AU - Sakamoto, Takafumi
AU - Sakamoto, Kazuo
AU - Kishi, Takuya
AU - Ide, Tomomi
AU - Sunagawa, Kenji
N1 - Funding Information:
This work was supported by Grandin-Aid from Translational Research Network Program [grant number B07 ], Grant-in-Aid for Scientific Research (S) from the Japan Society for the Promotion of Science [grant number 23220013 ], Research and development of supportive device technology for medicine using ICT, Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science [grant number 15K19383 ], and Actelion Academia Prize 2015.
Publisher Copyright:
© 2016 Elsevier Ireland Ltd
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/1/15
Y1 - 2017/1/15
N2 - Background Reducing myocardial damage is a prerequisite to prevent chronic heart failure after acute myocardial infarction (AMI). Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have potent anti-infarct effect, technical difficulties have precluded its clinical application. We developed a novel therapeutic strategy of intravenous VNS (iVNS) and examined whether iVNS administered prior to coronary reperfusion in a canine AMI model reduces infarct size and prevents heart failure. Methods and results In 35 mongrel dogs, we induced ischemia by ligating the left anterior descending coronary artery and then reperfused 3 h later (I/R). We transvenously placed a catheter electrode in the superior vena cava and adjusted the stimulation intensity to a level that induced bradycardia but maintained stable hemodynamics (continuous, 5.1 ± 2.1 V, 10 Hz). We administered iVNS from onset (iVNS-0, n = 7) or 90 min after onset (iVNS-90, n = 7) of ischemia until one hour after reperfusion. Four weeks after ischemia–reperfusion, iVNS markedly reduced infarct size (iVNS-0: 2.4 ± 2.1%, p < 0.05 and iVNS-90: 4.5 ± 4.5%, p < 0.05) compared with I/R control (I/R: 13.3 ± 2.5%), and improved cardiac performance and hemodynamics. Atrial pacing (n = 7) to abolish iVNS-induced bradycardia significantly attenuated the beneficial effects of iVNS. Conclusions Short-term iVNS delivered prior to coronary reperfusion markedly reduced infarct size and preserved cardiac function one month after AMI. The bradycardic effect plays an important role in the beneficial effect of iVNS. How other mechanisms contribute to the reduction of infarct size remains to be studied.
AB - Background Reducing myocardial damage is a prerequisite to prevent chronic heart failure after acute myocardial infarction (AMI). Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have potent anti-infarct effect, technical difficulties have precluded its clinical application. We developed a novel therapeutic strategy of intravenous VNS (iVNS) and examined whether iVNS administered prior to coronary reperfusion in a canine AMI model reduces infarct size and prevents heart failure. Methods and results In 35 mongrel dogs, we induced ischemia by ligating the left anterior descending coronary artery and then reperfused 3 h later (I/R). We transvenously placed a catheter electrode in the superior vena cava and adjusted the stimulation intensity to a level that induced bradycardia but maintained stable hemodynamics (continuous, 5.1 ± 2.1 V, 10 Hz). We administered iVNS from onset (iVNS-0, n = 7) or 90 min after onset (iVNS-90, n = 7) of ischemia until one hour after reperfusion. Four weeks after ischemia–reperfusion, iVNS markedly reduced infarct size (iVNS-0: 2.4 ± 2.1%, p < 0.05 and iVNS-90: 4.5 ± 4.5%, p < 0.05) compared with I/R control (I/R: 13.3 ± 2.5%), and improved cardiac performance and hemodynamics. Atrial pacing (n = 7) to abolish iVNS-induced bradycardia significantly attenuated the beneficial effects of iVNS. Conclusions Short-term iVNS delivered prior to coronary reperfusion markedly reduced infarct size and preserved cardiac function one month after AMI. The bradycardic effect plays an important role in the beneficial effect of iVNS. How other mechanisms contribute to the reduction of infarct size remains to be studied.
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U2 - 10.1016/j.ijcard.2016.10.074
DO - 10.1016/j.ijcard.2016.10.074
M3 - Article
C2 - 27816306
AN - SCOPUS:85006056623
VL - 227
SP - 704
EP - 710
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
ER -