title: Repeated cardiac pacing extends the time during which canine hearts are protected against ischaemia-induced arrhythmias: role of nitric oxide.
abstract: Right ventricular pacing in lightly anaesthetized dogs (4x5 min periods at a pacing rate of 220 beats/min) protects against the consequences of coronary artery occlusion when this is initiated 24 h after the pacing stimulus. The main purpose of the present experiments was to determine whether repeating the pacing stimulus, at a time when protection from the initial stimulus had faded (48 h), prolonged the protection afforded against ischaemia-induced ventricular arrhythmias and other ischaemic changes (epicardial ST-segment mapping; changes in the degree of electrical inhomogeneity in the ischaemic region). Dogs were paced on two occasions, with a 48 h period between and, at different times (48, 72 and 96 h) after the second pacing stimulus, were re-anaesthetized and subjected to occlusion of the left anterior descending coronary artery. There was a marked reduction in the severity of ischaemia-induced arrhythmias 48 and 72 h after the second pacing stimulus (reduction in occlusion-induced and reperfusion-induced ventricular fibrillation, e.g. at 72 h 0/11 during occlusion and only 3/11 following reperfusion, compared to 7/21 and 10/21 respectively in the controls P<0.05). The protection had disappeared 96 h following the second pacing stimulus. Changes in ST-segment elevation and in the degree of inhomogeneity largely followed these changes in the severity of ventricular arrhythmias. The results suggest the possibility of maintaining protection against life-threatening arrhythmias following coronary occlusion by repeating a preconditioning pacing stimulus. We also demonstrate that this prolonged protection afforded by repeated cardiac pacing is mediated by nitric oxide, since the marked antiarrhythmic effect observed, e.g. 72 h after the second pacing stimulus, was abolished when S-(2-aminoethyl)-isothiourea (AEST), a particularly selective inhibitor of iNOS, had been administered before coronary artery occlusion.
authors.affiliation: Department of Pharmacology, Albert Szent-Györgyi Medical University, Dóm tér 12, Szeged, H-6701, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Kis
authors.forename: A
authors.initials: A
authors.lastname: Végh
authors.forename: J G
authors.initials: JG
authors.lastname: Papp
authors.forename: J R
authors.initials: JR
authors.lastname: Parratt
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D013997:Time Factors; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
chemical_list: D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II