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 reperfusion-induced ventricular arrhythmias when this is initiated 24 h after the pacing stimulus. Now we have examined whether this delayed cardioprotection afforded by cardiac pacing is mediated through nitric oxide. 2. Twenty-two dogs were paced (4 x 5 min periods at 220 beats min(-1)) by way of the right ventricle, 24 h prior to a 25 min period of coronary artery occlusion. Nine of these dogs were given the inhibitor of induced nitric oxide synthase, aminoguanidine (50 mg kg(-1) i.v.), 0.5 h prior to coronary artery occlusion. Sham-operated non-paced dogs with and without aminoguanidine treatment served as controls. 3. Pacing markedly (P<0. 05) reduced arrhythmia severity (ventricular fibrillation, VF, during occlusion 15%; survival from the combined ischaemia-reperfusion insult 62%) compared to control, sham-operated, unpaced dogs (VF during occlusion 58%; survival 17%). This protection was attenuated by the administration 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 artery 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 nitric oxide synthase, contributes significantly to the delayed cardioprotection afforded by cardiac pacing.
Kis
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Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical University, Dóm tér 12, H6701 Szeged, Hungary.
Végh
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Papp
J
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Parratt
J
J
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control*; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D015427:Reperfusion Injury / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control; D018879:Ventricular Premature Complexes / Q000503:physiopathology / Q000517:prevention & control
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C004479:pimagedine