Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study

JACC Cardiovasc Interv. 2017 Aug 14;10(15):1511-1520. doi: 10.1016/j.jcin.2017.04.036.

Abstract

Objectives: The aim of this study was to investigate whether low-level tragus stimulation (LL-TS) treatment could reduce myocardial ischemia-reperfusion injury in patients with ST-segment elevation myocardial infarction (STEMI).

Background: The authors' previous studies suggested that LL-TS could reduce the size of myocardial injury induced by ischemia.

Methods: Patients who presented with STEMI within 12 h of symptom onset, treated with primary percutaneous coronary intervention, were randomized to the LL-TS group (n = 47) or the control group (with sham stimulation [n = 48]). LL-TS, 50% lower than the electric current that slowed the sinus rate, was delivered to the right tragus once the patients arrived in the catheterization room and lasted for 2 h after balloon dilatation (reperfusion). All patients were followed for 7 days. The occurrence of reperfusion-related arrhythmia, blood levels of creatine kinase-MB, myoglobin, N-terminal pro-B-type natriuretic peptide and inflammatory markers, and echocardiographic characteristics were evaluated.

Results: The incidence of reperfusion-related ventricular arrhythmia during the first 24 h was significantly attenuated by LL-TS. In addition, the area under the curve for creatine kinase-MB and myoglobin over 72 h was smaller in the LL-TS group than the control group. Furthermore, blood levels of inflammatory markers were decreased by LL-TS. Cardiac function, as demonstrated by the level of N-terminal pro-B-type natriuretic peptide, the left ventricular ejection fraction, and the wall motion index, was markedly improved by LL-TS.

Conclusions: LL-TS reduces myocardial ischemia-reperfusion injury in patients with STEMI. This proof-of-concept study raises the possibility that this noninvasive strategy may be used to treat patients with STEMI undergoing primary percutaneous coronary intervention.

Keywords: acute myocardial infarction; inflammation; ischemia-reperfusion injury; low-level vagal stimulation; ventricular arrhythmia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects*
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control*
  • Biomarkers / blood
  • China
  • Creatine Kinase, MB Form / blood
  • Echocardiography
  • Electrocardiography
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / diagnosis
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myoglobin / blood
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Proof of Concept Study
  • Prospective Studies
  • Recovery of Function
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / physiopathology
  • ST Elevation Myocardial Infarction / therapy*
  • Stroke Volume
  • Time Factors
  • Transcutaneous Electric Nerve Stimulation / adverse effects
  • Transcutaneous Electric Nerve Stimulation / methods*
  • Treatment Outcome
  • Vagus Nerve Stimulation / adverse effects
  • Vagus Nerve Stimulation / methods*
  • Ventricular Function, Left

Substances

  • Biomarkers
  • Inflammation Mediators
  • Myoglobin
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Creatine Kinase, MB Form