• Mária Kovács, Attila Kiss, Márton Gönczi, Gottfried Miskolczi, György Seprényi, József Kaszaki, Mark J Kohr, Elizabeth Murphy, and Ágnes Végh.
• Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
• Plos One. 2015 Jan 1; 10 (4): e0122243.

Background And PurposeTo provide evidence for the protective role of inorganic nitrite against acute ischaemia and reperfusion-induced ventricular arrhythmias in a large animal model.Experimental ApproachDogs, anaesthetized with chloralose and urethane, were administered intravenously with sodium nitrite (0.2 µmol kg(-1) min(-1)) in two protocols. In protocol 1 nitrite was infused 10 min prior to and during a 25 min occlusion of the left anterior descending (LAD) coronary artery (NaNO2-PO; n = 14), whereas in protocol 2 the infusion was started 10 min prior to reperfusion of the occluded vessel (NaNO2-PR; n = 12). Control dogs (n = 15) were infused with saline and subjected to the same period of ischaemia and reperfusion. Severities of ischaemia and ventricular arrhythmias, as well as changes in plasma nitrate/nitrite (NOx) levels in the coronary sinus blood, were assessed throughout the experiment. Myocardial superoxide and nitrotyrosine (NT) levels were determined during reperfusion. Changes in protein S-nitrosylation (SNO) and S-glutathionylation were also examined.Key ResultsCompared with controls, sodium nitrite administered either pre-occlusion or pre-reperfusion markedly suppressed the number and severity of ventricular arrhythmias during occlusion and increased survival (0% vs. 50 and 92%) upon reperfusion. There were also significant decreases in superoxide and NT levels in the nitrite treated dogs. Compared with controls, increased SNO was found only in NaNO2-PR dogs, whereas S-glutathionylation occurred primarily in NaNO2-PO dogs.ConclusionsIntravenous infusion of nitrite profoundly reduced the severity of ventricular arrhythmias resulting from acute ischaemia and reperfusion in anaesthetized dogs. This effect, among several others, may result from an NO-mediated reduction in oxidative stress, perhaps through protein SNO and/or S-glutathionylation.

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