Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate‐mediated attenuation

Abstract

Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min −1 ), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 ± 9 Ω, from 611 ± 24 Ω, n = 16) when compared with intact control dogs (+43 ± 5 Ω, from 620 ± 20 Ω, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 ± 11 to 193 ± 15 beats min −1 ) and MEI (+12 ± 1.1 Ω, from 663 ± 18 Ω). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 ± 6 to 73 ± 9 beats min −1 ) and MEI (−16 ± 2 Ω, from 700 ± 44 Ω). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 ± 0.03 versus 0.15 ± 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 ± 4.2 versus 65.8 ± 5.9 ms; QTc, 340 ± 8 versus 254 ± 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand.

Device-Based Autonomic Modulation in Arrhythmia Patients: the Role of Vagal Nerve Stimulation

“…Reduction of electrotonic coupling has been linked to arrhythmogenesis in ischemia [47]. VNS preserves electrotonic coupling during ischemia along with reducing ST segment elevations and dispersion of repolarization [47]. Interestingly, in the same study, pacing attenuated the protective effects of VNS whereas bilateral stellectomy did not, further supporting the notion that VNS mediates its effects by direct innervation of the heart rather than by causing reflex activation of afferent fibers in the central nervous system.…”

“…Reduction of electrotonic coupling has been linked to arrhythmogenesis in ischemia [47]. VNS preserves electrotonic coupling during ischemia along with reducing ST segment elevations and dispersion of repolarization [47].…”

“…When cholinergic effects on heart rate (HR) suppression are eliminated with atropine, VNS causes a surprising increase in HR, primarily through the release of vasoactive intestinal peptide (VIP) [36•, 47, 54]. Additionally, VIP does not seem to protect against ventricular arrhythmias and does not affect VF threshold or ventricular effective refractory period [36•].…”

Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for β-adrenoceptor mediated enhanced coupling during exercise testing

“…As has previously been described, a computer controlled circuit developed in this laboratory was used to measure the complex electrical impedance of the myocardium (Howie et al, 2001 ; Dzwonczyk et al, 2004 ; Del Rio et al, 2005 , 2008a , b ). In short, using a bipolar pacing lead (see above) the myocardium was probed with a sub-threshold zero-mean bipolar current, consisting of two rectangular pulse of alternating polarity (± 5 μA, 100 μs wide) generated 200 ms apart.…”

Neural control hierarchy of the heart has not evolved to deal with myocardial ischemia

“…In a review by Eckberg (9) it was pointed out that "Vagal and sympathetic cardiovascular control is deranged profoundly in patients with congestive heart failure." A study by del Rio et al (8) examined the electrical changes induced by myocardial ischemia in dogs, concluding that "Parasympathetic activity during acute coronary occlusion can protect against ischemiainduced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear." These studies illustrate the fact that experimental or clinical observations in the event of myocardial ischemia, particularly of heart rate, provide the manifestations of a derangement of the neural control system of the heart, but they do not provide the underlying mechanisms.…”