Donors of nitric oxide mimic effects of ischaemic preconditioning on reperfusion induced arrhythmias in isolated rat heart.
NO has been implicated in the mechanism of ischaemic preconditioning. To verify this hypothesis further we have attempted to reproduce effects of ischaemic preconditioning by nitric oxide donors administration prior to the ischaemia. The effect of glyceryl trinitrate (GTN) and 3-morpholino-sydnonimine-hydrochloride (SIN-1), NO donors, on reperfusion induced ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff perfused rat hearts subjected to 10 min regional ischaemia followed by 10 min reperfusion were examined.


RESULTS
GTN, 500 microM and SIN-1, 10 microM, administered for 5 min and washed for another 5 min prior to ischaemia (to mimic ischaemic preconditioning), almost completely abolished reperfusion induced VF. GTN and SIN-1, administered at the time of reperfusion, increased the incidence of sustained VF and the duration of VT and VF. When given 5 min before the ischaemia and throughout the ischaemia and the reperfusion, SIN-1 abolished VF. Adenosine, 10 microM, applied according to the above three protocols, did not affect reperfusion arrhythmias, although adenosine induced changes in coronary flow and post-ischaemic reflow were similar to those produced by the NO donors. In conclusions: (1) NO is able to mimic the effect of ischaemic preconditioning on reperfusion arrhythmias in rat heart, supporting the view that NO may be one of the endogenous substances triggering ischaemic preconditioning; (2) In crystalloid-perfused heart, NO may be deleterious when its administration is restricted to the reperfusion period.
Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
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M
Bilińska
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Maczewski
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Beresewicz
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin; D000241:Adenosine