Repeated cardiac pacing extends the time during which canine hearts are protected against ischaemia-induced arrhythmias: Role of nitric oxide

Right ventricular pacing in lightly anaesthetized dogs (4 x 5 min periods a t a pacing rate of 220 beats/min) protects against the consequences of coro nary artery occlusion when this is initiated 24 h after the pacing stimulus . The main purpose of the present experiments was to determine whether repe ating the pacing stimulus, at a time when protection from the initial stimu lus had faded (48h;), prolonged the protection afforded against ischaemia-i nduced ventricular arrhythmias and other ischaemic changes (epicardial ST-s egment mapping; changes in the degree of electrical inhomogeneity in the is chaemic region). Dogs were paced on two occasions, with a 48 h period betwe en and, at different times (48, 72 and 96 h) after the second pacing stimul us, were re-anaesthetized and subjected to occlusion of the left anterior d escending 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 fibrill ation, e.g. at 72 h 0/11 during occlusion and only 3/11 following reperfusi on, compared to 7/21 and 10/21 respectively in the controls; P<0.05). The p rotection had disappeared 96h following the second pacing stimulus. Changes in ST-segment elevation and in the degree of inhomogeneity largely followe d these changes in the severity of ventricular arrhythmias. The results sug gest the possibility of maintaining protection against life-threatening arr hythmias following coronary occlusion by repeating a preconditioning pacing stimulus. We also demonstrate that this prolonged protection afforded by r epeated cardiac pacing is mediated by nitric oxide, since the marked antiar rhythmic effect observed, e.g, 72 h after the second pacing stimulus, was a bolished when S-(2-aminoethyl)-isothiourea (AEST), a particularly selective inhibitor of iNOS, had been administered before coronary artery occlusion. (C) 1999 Academic Press.