Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model (Oxford CEBM Level 5)
PubMed 2019002 · doi:10.1161/01.res.68.5.1471
What was done
Myocardial infarction was induced in 161 dogs, leaving 105 survivors evaluated 1 month later with an exercise stress test and 2-minute circumflex coronary artery occlusion. The 59 dogs that developed ventricular fibrillation were assigned to either a control group (n = 24) or chronic implantation of a right cervical vagal nerve stimulation device (n = 35; 5 excluded for electrode malfunction, leaving n = 30). During repeat exercise-induced ischemia testing, the incidence of ventricular fibrillation was measured during active vagal stimulation and compared with controls, an internal unstimulated re-test, and a subgroup tested during constant atrial pacing (n = 9).
What was found
Vagal stimulation reduced peak exercise-ischemia heart rate from 255 ± 33 to 170 ± 36 beats/min (a decrease of ~75 beats/min, p < 0.001). During repeat testing, ventricular fibrillation occurred in 22 of 24 (92%) control dogs compared with 3 of 30 (10%) dogs receiving vagal stimulation (p < 0.001). In subsequent testing without stimulation, ventricular fibrillation recurred in 26 of 30 (87%) dogs (p < 0.001 vs stimulation). When heart rate was held constant by atrial pacing, vagal stimulation remained protective, with 5 of 9 (55%) dogs surviving the ischemic challenge (p = 0.015).
Why it matters
This study provides direct proof-of-concept in conscious post-infarction animals that vagal nerve stimulation protects against ischemia-induced ventricular fibrillation through both heart-rate reduction and independent anti-adrenergic electrophysiological mechanisms.
Limits
The study is restricted to a canine model of acute coronary occlusion, which may not fully capture the complexity of human chronic ischemic heart disease and spontaneous arrhythmias. Mechanistic sub-analyses like fixed-rate pacing were small (n = 9), and device failure occurred in 5 of 35 instrumented animals.
Cited by
- supports In canine models of exercise ischemia, vagal nerve stimulation or prior exercise training prevents ventricular fibrillation and sudden cardiac death during acute coronary artery occlusion.