Aims: 

Since the early 1990 we have been extensively examining the role of nitric oxide (NO) in cardioprotection, particularly against the acute ischaemia and reperfusion (I/R)-induced severe ventricular arrhythmias. The achievements of these twenty years of research are now summarised.

Methods: 

In choralose-urethane anaesthetised dogs ischaemia was induced by a 25 min occlusion of the anterior descending branch of the left coronary artery (LAD) followed by rapid reperfusion. The severity of ischaemia and of arrhythmias, changes in NO availability and in the formation of superoxide and peroxynitrite resulting from I/R, were determined. The role of NO was assessed under various experimental conditions; e.g. in the early and delayed effects of preconditioning (PC) using inhibitors of NO generation, and in situations when NO availability was increased prior to and during I/R by drugs, such as NO donors, peroxynitrite or sodium nitrite.

Results: 

Inhibition of NO synthesis abolished both the early and the delayed antiarrhythmic effects of preconditioning induced by brief coronary artery occlusions, rapid cardiac pacing or heavy physical exercise, indicating a role for NO in the PC-induced cardioprotection. Moreover, increasing local NO availability by drugs results in a marked antiarrhythmic protection, indicating that the replacement of NO loss during I/R attenuates the generation of arrhythmias. This effect is due, in part, to the inhibition of superoxide production following reperfusion.

Conclusion: 

NO is a cardioprotective molecule and preservation of NO availability during I/R results in profound antiarrhythmic effect perhaps by attenuating the harmful consequences of oxidative stress.