Peroxynitrite decreases arrhythmias induced by ischaemia reperfusion in anaesthetized dogs, without involving mitochondrial KATP channels.
OBJECTIVE
Exogenous peroxynitrite from nanomolar to micromolar concentrations exerts cardioprotection. Here, we have assessed its effects on ischaemia- and reperfusion-induced ventricular arrhythmias in vivo and a possible role for mitochondrial K(ATP) channels in these effects, using the channel inhibitor 5-hydroxydecanoate (5-HD).


METHODS
Chloralose-urethane-anaesthetized dogs were treated twice for 5 min with peroxynitrite (100 nM, by intracoronary infusions) in both the absence and presence of 5-HD (150 microg kg(-1) min(-1)), and then subjected to 25 min occlusion of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, as well as the levels of nitrotyrosine were assessed and compared with a group of control dogs, subjected only to a 25 min occlusion and reperfusion insult.


RESULTS
Compared with controls, infusion of peroxynitrite markedly suppressed the number of ventricular premature beats (388+/-88 vs 133+/-44), the incidence of ventricular fibrillation both during occlusion (50% vs 10%) and reperfusion (100% vs 44%), and increased survival (0% vs 50%; all P<0.05). The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) during occlusion and nitrotyrosine levels on reperfusion were significantly less in the peroxynitrite-treated dogs than in the controls. 5-HD did not modify the cardioprotective effects of peroxynitrite.


CONCLUSIONS
Exogenous peroxynitrite provided antiarrhythmic protection in vivo, which might have been on account of a reduction in endogenous peroxynitrite formation. This protection seemed not to be mediated through mitoK(ATP) channels.
1Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Hungary.
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Kiss
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Juhász
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Huliák
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Végh
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D003652:Decanoic Acids / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012720:Severity of Illness Index; D015996:Survival Rate; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; C052853:5-hydroxydecanoic acid