The acute reduction in nitric oxide release following repetitive myocardial stunning is not associated with the production of peroxynitrite

The fall in endothelial nitric oxide (NO) production following ischaemia-reperfusion (IR) has been hypothesised to result from the reaction of NO and superoxide with the formation of peroxynitrite (ONOO^-). We aimed to study the generation of NO and ONOO^- in response to repetitive episodes of IR leading to myocardial stunning (MS). MS was induced in 6 swine (34-39Kg) by ten 2-minute occlusions of the circumflex artery. Four sham operated animals acted as controls. Regional myocardial function was measured using segment shortening. Paired aortic and local coronary venous blood samples were taken at baseline, immediately after reperfusion and over the following 6 hrs for NO analysis. Plasma nitrotyrosine (the "foot print" of peroxynitrite attack on proteins) was assessed by ELISA, 1 and 5 minutes after the final reperfusion. Tissue samples from the ischaemic and control areas were also immunostained for nitrotyrosine 6 hours post reperfusion. Results: Myocardial function fell to 53 ± 8% (mean ± SEM) of baseline 30 min post final reperfusion, recovering to 92 ± 8.7% at 6 hours and was associated with a significant fall in NO production from baseline compared with controls (-120 +/-13.5% vs. -48 +/- 9%, mean +/-SEM, p