"Dose"-dependency and temporal characteristics of protection by ischaemic preconditioning against ischaemia-induced arrhythmias in rat hearts.

Brief episodes of ischaemia and reperfusion (preconditioning) can increase the resistance of the myocardium to ischaemic injury. We investigated the temporal characteristics of anti-arrhythmic protection by preconditioning. Rat hearts underwent regional ischaemia (+/- reperfusion) of the left coronary territory. Control isolated blood-perfused hearts underwent 40 min ischaemia; in the preconditioned groups this was preceded by one, two or three cycles of 5 min ischaemia and 5 min reperfusion. Control anaesthetized rats underwent 60 min ischaemia; this was preceded by three cycles of 3 min ischaemia and 3 min reperfusion in the preconditioned group. Preconditioning led to: (i) the abolition of ventricular fibrillation in both in vivo and in vitro preparations; (ii) a reduced incidence of ventricular tachycardia (from 100% to 8% in vitro and 100% to 25% in vivo); and (iii) a reduced incidence of ventricular premature beats (from 246 +/- 36 to 8 +/- 5 in vitro and 85 +/- 21 to 24 +/- 13 in vivo). In isolated hearts protection was proportional to the number of preconditioning cycles. Although preconditioning caused a dramatic reduction in the severity of arrhythmias it did not result in any significant alteration in their temporal profiles. We conclude that protection by preconditioning against ischaemia-induced arrhythmias is "dose"-dependent in rat hearts in vitro and results in an absolute reduction in the severity of ischaemia-induced arrhythmias rather than an alteration in their time-course, both in vivo and in vitro.