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 fibril lation are able to mimic preconditioning by ischemia and thereby protect th e isolated blood-perfused heart against ischemia-induced injury and (ii) ch aracterize the effects of these interventions on cardiac metabolism, To thi s end, isolated, blood-perfused (2.4 ml/min), paced (360 beats/min) rat hea rts (n = 6/group), were aerobically perfused for 20 min. Hearts were then r andomized to four groups: (i) a further 16 min aerobic perfusion (UC, untre ated controls), (ii) ischemic preconditioning (IP, 3 min ischemia + 3 min r eperfusion followed by i min ischemia + 5 min reperfusion), (iii) electrica lly 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 greater than or equal to 600 beats/min (RP, 3 min rapid pacing 3 min normal heart rate followed by 5 ruin rapid pacing + 5 min normal hear t 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 ass ayed for high energy phosphates and noradrenaline content. Time-to-50% cont racture 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 1 2.8 +/- 1.2 min respectively). Post-ischemic left ventricular developed pre ssure (LVDP) in untreated controls recovered to only 19.9 +/- 8.4% of its p re-ischemic value whereas with IP, VF and RP substantial and similar improv ements were observed (60.3 +/- 7.4, 56.2 +/- 5.7 and 45.3 +/- 10.3%, respec tively, P<0.01). This protection was achieved without any significant deple tion of high energy phosphates during VF or RP. Noradrenaline was essential ly 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 ar e as effective as brief ischemia in protecting the heart against injury dur ing ischemia and reperfusion. In contrast to IF, this protection can be ach ieved without the exacerbation of ischemic contracture and without inducing ischemia during the preconditioning period. (C) 1999 Academic Press.