Intravenous electrical vagal nerve stimulation prior to coronary reperfusion in a canine ischemia-reperfusion model markedly reduces infarct size and prevents subsequent heart failure

Takahiro Arimura, Keita Saku, Takamori Kakino, Takuya Nishikawa, Takeshi Tohyama, Takafumi Sakamoto, Kazuo Sakamoto, Takuya Kishi, Tomomi Ide, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)704-710
Number of pages7
JournalInternational Journal of Cardiology
Volume227
DOIs
Publication statusPublished - Jan 15 2017

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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