1. Depressant effects of fast sodium channel blockade on the electrical activity of ischaemic canine ventricle: mediation by the sympathetic nervous system.
- Author
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Gilmour RF Jr, Morrical DG, Ertel PJ, Maesaka JF, and Zipes DP
- Subjects
- Action Potentials drug effects, Animals, Blood Pressure drug effects, Dogs, Electrocardiography, Female, Heart innervation, Heart physiopathology, Heart Rate drug effects, Male, Stellate Ganglion physiology, Time Factors, Coronary Disease physiopathology, Ion Channels drug effects, Sodium metabolism, Tetrodotoxin pharmacology
- Abstract
In this study we examined the possibility that local anaesthetic agents such as tetrodotoxin may exacerbate electrical changes during acute myocardial ischaemia by inhibiting fast sodium channels, both in cardiac cells and in sympathetic nerve terminals. Bipolar electrograms were recorded during serial 2 to 5 min occlusions of the left anterior descending coronary artery in open-chest, anaesthetised dogs. Tetrodotoxin (1 or 2 micrograms X kg-1 iv) given prior to occlusion did not affect activation times or electrograms in normal myocardium but exacerbated activation delay and loss of electrogram amplitude during ischaemia. Bilateral stellectomy reversed the effects of tetrodotoxin during ischaemia. Tetrodotoxin (1 microgram X kg-1 iv) reduced changes in heart rate and mean arterial blood pressure produced by stellate ganglia stimulation. Intracoronary infusion of tetrodotoxin (10(-5) mol X litre-1) during normal perfusion lengthened mean effective ventricular refractory periods and propranolol (0.5 mg X kg-1 iv) or bilateral stellectomy prevented this effect. Thus, tetrodotoxin appeared to increase ventricular refractoriness and exacerbate ischaemia-induced activation delay by inhibiting sympathetic nerve activity. Other agents with local anaesthetic properties may have similar effects.
- Published
- 1984
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