Pacing-induced delayed protection against arrhythmias is attenuated by aminoguanidine, an inhibitor of nitric oxide synthase

1 Cardiac pacing, in anaesthetized dogs, protects against ischaemia and rep erfusion-induced ventricular arrhythmias when this is initiated 24 h after the pacing stimulus. Now we have examined whether this delayed cardioprotec tion afforded by cardiac pacing is mediated through nitric oxide. 2 Twenty-two dogs were paced (4x5 min periods at 220 beats min(-1)) by way of the right ventricle, 24 h prior to a 25 min period of coronary artery oc clusion. Nine of these dogs were given the inhibitor of induced nitric oxid e synthase, aminoguanidine (50 mg kg(-1) i.v.), 0.5 h prior to coronary art ery occlusion. Sham-operated non-paced dogs with and without aminoguanidine treatment served as controls. 3 Pacing markedly (P<0.05) reduced arrhythmia severity (ventricular fibrill ation, VF, during occlusion 15%; survival from the combined ischaemia-reper fusion insult 62%) compared to control, sham-operated, unpaced dogs (VF dur ing occlusion 58%; survival 17%). This protection was attenuated by the adm inistration of aminoguanidine prior to coronary artery occlusion (survival from the combined ischaemia-reperfusion insult 11%, which was significantly (P<0.05) less than in the paced dogs not given aminoguanidine and similar to the controls). Aminoguanidine had no significant effects on coronary art ery occlusion when given to dogs that had not been paced. In the dose used aminoguanadine transiently elevated systemic arterial pressure by a mean of 20 mmHg and reduced heart rate by a mean of 22 beats min(-1). 4 These results suggest that nitric oxide, probably derived from induced ni tric oxide synthase, contributes significantly to the delayed cardioprotect ion afforded by cardiac pacing.