Cardioprotection: intermittent ventricular fibrillation and rapid pacing can induce preconditioning in the blood-perfused rat heart.

The aim of the study was to use the isolated blood-perfused rat heart to: (i) determine whether brief intermittent rapid pacing and ventricular fibrillation are able to mimic preconditioning by ischemia and thereby protect the isolated blood-perfused heart against ischemia-induced injury and (ii) characterize the effects of these interventions on cardiac metabolism. To this end, isolated, blood-perfused (2.4 ml/min), paced (360 beats/min) rat hearts (n = 6/group), were aerobically perfused for 20 min. Hearts were then randomized to four groups: (i) a further 16 min aerobic perfusion (UC, untreated controls), (ii) ischemic preconditioning (IP, 3 min ischemia + 3 min reperfusion followed by 5 min ischemia + 5 min reperfusion), (iii) electrically induced ventricular fibrillation (VF, 3 min fibrillation + 3 min sinus rhythm followed by 5 min fibrillation + 5 min sinus rhythm) and (iv) rapid pacing at > or = 600 beats/min (RP, 3 min rapid pacing + 3 min normal heart rate followed by 5 min rapid pacing + 5 min normal heart rate). Hearts were then subjected to 35 min of zero-flow, global ischemia (37 degrees C) and 40 min reperfusion. In parallel studies, blood samples were collected during the first 3 min of treatment and plasma taken for the analysis of noradrenaline. The hearts were then immediately frozen and assayed for high energy phosphates and noradrenaline content. Time-to-50% contracture during ischemia was 13.2 +/- 0.8 min in controls; this was reduced to 6.3 +/- 1.1 min by IP but was unaffected by VF or RP (12.4 +/- 1.1 and 12.8 +/- 1.2 min respectively). Post-ischemic left ventricular developed pressure (LVDP) in untreated controls recovered to only 19.9 +/- 8.4% of its pre-ischemic value whereas with IP, VF and RP substantial and similar improvements were observed (60.3 +/- 7.4, 56.2 +/- 5.7 and 45.3 +/- 10.3%, respectively, P < 0.01). This protection was achieved without any significant depletion of high energy phosphates during VF or RP. Noradrenaline was essentially unchanged in controls and with RP, but VF caused a loss from tissue and a large elevation in the plasma. Our results suggest that both RP and VF are as effective as brief ischemia in protecting the heart against injury during ischemia and reperfusion. In contrast to IP, this protection can be achieved without the exacerbation of ischemic contracture and without inducing ischemia during the preconditioning period.