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Donors of nitric oxide mimic effects of ischaemic preconditioning on reperfusion induced arrhythmias in isolated rat heart

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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 μM and SIN-1, 10 μM, 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 μM, 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.

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Correspondence to Andrzej Beręsewicz.

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Bilińska, M., Mączewski, M. & Beręsewicz, A. Donors of nitric oxide mimic effects of ischaemic preconditioning on reperfusion induced arrhythmias in isolated rat heart. Mol Cell Biochem 160, 265–271 (1996).

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Key words

  • nitric oxide
  • preconditioning
  • reperfusion arrhythmias
  • isolated rat heart
  • SIN-1
  • glyceryl trinitrate
  • adenosine
  • nitric oxide toxicity