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

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.

Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death

“…In autonomically-intact dogs, spontaneous ischaemia-induced VF increased in vivo following i.v. atropine (Goldstein et al 1973), with similar conclusions drawn from control experiments in the dog model of SCD (Schwartz et al 1984;Vanoli et al 1991). This is supported by data during direct VNS where atropine abolished protection (Yoon et al 1977).…”

“…The seminal work by Schwartz and his group provided insight in the association between autonomic tone and arrhythmic death in a conscious canine model of sudden ischaemic cardiac death. It was found that concomitant vagus nerve stimulation significantly prevented ischaemia-induced VF (Vanoli et al 1991). Of equal significance, it was found that baseline baroreflex sensitivity was high in animals resistant to VF and low in susceptible animals .…”

“…Kolman (Kolman et al 1976), however, showed that vagal stimulation alone did not affect the VF threshold but prevented the decrease in VF threshold induced by simultaneous sympathetic stimulation. Others have noted that the anti-arrhythmic effects of vagal stimulation are most pronounced during sympathetic activation (Vanoli et al 1991). The effects of sympathetic and vagal stimulation have a different time course of action and the interactions between the two are complicated and unpredictable (Levy 1997).…”

“…The authors also found that muscarinic blockade with atropine promoted premature ventricular contractions, VT and VF in animals with no arrhythmia during control. The group also studied the effects of direct VNS on the occurrence of SCD in dogs that survived MI (Vanoli et al 1991). Right VNS, applied before and throughout coronary artery occlusion, reduced the occurrence of VF from 92% in control to 10% during VNS.…”

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

“…In animals, electrical stimulation of the cervical vagus nerve has been shown to evoke cardiovascular effects, for example by lowering the ventricular fibrillation threshold (Brack et al, 2013). Moreover, VNS is known to reduce incidence of ventricular arrhythmias and mortality during ischemia (Brack et al, 2013) and prevent sudden cardiac death in dogs with myocardial infarction (Vanoli et al, 1991). VNS has also been investigated in animal models of chronic heart failure, a condition characterised by a sustained increase in sympathetic drive and a concurrent withdrawal of parasympathetic activity (Triposkiadis et al, 2009).…”