CoChat
Sign Up
Cited by 681Vagus Nerve Stimulation ResearchHeart Rate Variability and Autonomic ControlCardiac pacing and defibrillation studies

Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction.

Open access
Vanoli, E, De Ferrari, G M, Stramba-Badiale, M, Hull, S S, Foreman, R D, Schwartz, P J·1991·Circulation Research
DOI 10.1161/01.res.68.5.1471
Open this paper in CoChat — free accountOpen PDF

Abstract

The interest for the antifibrillatory effect of vagal stimulation has been largely limited by the fact that this concept seemed restricted to acute experiments in anesthetized animals. To explore the potentially protective role of vagal stimulation in conscious animals we developed a chronically implantable device to be placed around the cervical right vagus. An anterior myocardial infarction was produced in 161 dogs; 1 month later an exercise stress test was performed on the 105 survivors. Toward the end of the test the circumflex coronary artery was occluded for 2 minutes. Fifty-nine (56%) dogs developed ventricular fibrillation and, before this test was repeated, were assigned either to a control group (n = 24) or to be instrumented with the vagal device (n = 35). Five dogs were excluded because of electrode malfunction. Compared with the heart rate level attained after 30 seconds of occlusion during exercise in the control test, vagal stimulation led to a decrease of approximately 75 beats/min (from 255 +/- 33 to 170 +/- 36 beats/min, p less than 0.001). In the control group 22 (92%) of 24 dogs developed ventricular fibrillation during the second exercise and ischemia test. By contrast, during vagal stimulation ventricular fibrillation occurred in only 3 (10%) of the 30 dogs tested and recurred in 26 (87%) during an additional exercise and ischemia test in the control condition (p less than 0.001 versus the vagal stimulation test; internal control analysis). Combined analysis of the tests performed in the control condition showed that ventricular fibrillation was reproducible in 48 (89%) of the 54 dogs tested. The protective effect of vagal stimulation was also significant in the group comparison analysis and even after exclusion of those four dogs in which ventricular fibrillation was not reproducible (92% versus 11.5%, control versus vagal stimulation, p less than 0.001). When heart rate was kept constant by atrial pacing, the vagally mediated protection was still significant (p = 0.015) as five (55%) of nine dogs survived the test. This study shows that vagal stimulation, performed shortly after the onset of an acute ischemic episode in conscious animals with a healed myocardial infarction, can effectively prevent ventricular fibrillation. This striking result seems to depend on multiple mechanisms having a synergistic action. The decrease in heart rate is an important but not always essential protective mechanism. The electrophysiological effects secondary to the vagally mediated antagonism of the sympathetic activity on the heart are likely to play a major role.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/01.res.68.5.1471

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Post-exercise recovery is a critical phase for sudden cardiovascular events, predominantly in the 30 minutes immediately following vigorous exercise, attributable to increased sympathetic and decreased parasympathetic nerve activity.

    “In particular, post-exercise recovery is a critical phase for sudden cardiovascular events, predominantly in the 30 minutes immediately following vigorous exercise, 5 which is attributable to increased sympathetic and decreased parasympathetic nerve activity.6”

    From Caffeine delays autonomic recovery following acute exercise (2015) · cites this paper as [6]

    The Electrophysiological Effects section describes vagal activity as protective against arrhythmias in the presence of elevated sympathetic activity, supporting the proposed autonomic mechanism in general. But this study concerns dogs undergoing exercise and induced myocardial ischemia; it does not establish that a sympathetic–parasympathetic imbalance causes events during post-exercise recovery. The 30-minute timing is attached to a different citation in the citing sentence. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 13

  1. [4]4. Janse MJ, Schwartz PJ, Wilms-Schopman F, Peters RJG, Durrer D: Effects of unilaterate stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs. Circulation 1985;72:585-595
  2. [11]11. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, Multicenter Postinfarction Research Group: Heart rate variability: A variable predicting mortality following acute myocardial infarction. Am J Cardiol 1987;59:256-262
  3. [20]20. Kent KM, Smith ER, Redwood DR, Epstein SE: Electrical stability of acutely ischemic myocardium: Influences of heart rate and vagal stimulation. Circulation 1973;47:291-298
  4. [21]21. Myers RW, Pearlman AS, Hyman RM, Goldstein RA, Kent KM, Goldstein RE, Epstein SE: Beneficial effect of vagal stimulation and bradycardia during experimental acute myo- cardial ischemia. Circulation 1974;49:943-947
  5. [22]22. Verrier RL, Lown B: Sympathetic-parasympathetic interac- tions and ventricular electrical stability, in Schwartz PJ, Brown AM, Malliani A, Zanchetti A (eds): Neural Mechanisms in Cardiac Arrhythmias. New York, Raven Press, Publishers, 1978, pp 75-85
  6. [38]38. Verrier RL, Hohnloser SH: How is the nervous system impli- cated in the genesis of cardiac arrhythmias?, in Hearst DG, Manning AS, Janse MJ (eds): Life-Threatening Arrhythmias During Ischemia and Infarction. New York, Raven Press, Publishers, 1987, pp 153-168
  7. [48]48. Gonzales-Serrato H, Alanis J: La acci6n de los nervios cardi- acos y de la acetilacolina sobre el automatismo del coraz6n. Acta Physiol Latinoam 1962;12:139-152
  8. [50]50. Carrier GO, Bishops VS: The interaction of acetylcholine and norepinephrine on heart rate. JPharmacol Exp Ther 1972;180: 31-37
  9. [51]51. Fleming JW, Watanabe AM: Biochemical mechanisms of parasympathetic regulation of cardiac function, in Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE (eds): The Heart and Cardiovascular System. New York, Raven Press, Publishers, 1986, pp 1679-1688
  10. [59]59. Levy MN: Sympathetic-parasympathetic interactions in the heart. Circ Res 1972;29:437-445
  11. [64]64. Waxman MB, Wald RW: Termination of ventricular tachycar- dia by increase in cardiac vagal drive. Circulation 1977;56: 385-394
  12. [66]66. Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM: A cardio-cardiac sympatho-vagal reflex in the cat. Circ Res 1973;32:215-220
  13. [82]82. Redwood DR, Smith ER, Epstein SE: Coronary artery occlu- sion in the conscious dog: Effects of alterations in heart rate and arterial pressure on the degree of myocardial ischemia. Circulation 1972;46:323-332

Cited by

Sorted by citations

Related

Authors
Vanoli, E., De Ferrari, G. M., Stramba-Badiale, M., Hull, S. S., Foreman, R. D., & Schwartz, P. J.
Affiliations
  • University of Oklahoma (US)
  • Department of Physiology and Biophysics, University of Oklahoma, Oklahoma City.
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1991-05
Volume
68
Issue
5
Pages
1471-1481
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/01.res.68.5.1471
OpenAlex
W2123181530
Cited by
681
References
73
Citations by year
2026: 8 · 2025: 11 · 2024: 10 · 2023: 22 · 2022: 18 · 2021: 19 · 2020: 20 · 2019: 23 · 2018: 16 · 2017: 22 · 2016: 29 · 2015: 42 · 2014: 35 · 2013: 28 · 2012: 25
FWCI
8.20
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
  • National Institutes of Health (5p01hl033727-03)
  • National Heart, Lung, and Blood Institute (HL33727)
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Keywords
vagus nerve stimulation, sudden cardiac death prevention, ventricular fibrillation, myocardial infarction, anterior myocardial infarction, coronary artery occlusion, exercise stress testing, heart rate reduction, atrial pacing, conscious dogs, ischemia-induced arrhythmia, antifibrillatory effect, atrial fibrillation prevention
MeSH terms
Animals, Blood Pressure, Cardiac Pacing, Artificial, Death, Sudden, Dogs, Electric Stimulation, Electrocardiography, Heart Rate, Hemodynamics, Myocardial Infarction, Vagus Nerve, Ventricular Fibrillation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review