Preconditioning and post-ischaemic contractile dysfunction: the role of impaired oxygen delivery vs extracellular...

The aim of the present study was to identify components of ischaemia involved in the induction of preconditioning. Isolated rat hearts (n = 8 per group) were perfused with bicarbonate buffer. Following 10 min aerobic perfusion they were randomised and subjected to 5 min periods during which the perfusion conditions were: (i) normal aerobic perfusion (controls); (ii) zero flow ischaemia; (iii) low flow ischaemia (10% of control O2 delivery); (iv) hypoxia (10% of control O2 delivery); or (v) acidosis (pH 6.4). After these periods of "preconditioning", all hearts underwent 5 min aerobic perfusion followed by 40 min zero flow global ischaemia and 35 min reperfusion. Contractile function was measured at the beginning and at the end of the experiment. Despite profound differences in coronary flow during preconditioning, substantial and similar protection was observed in all groups preconditioned by transiently limiting oxygen delivery. Recovery of cardiac output was 66.7 +/- 6.3%, 58.7 +/- 5.1% and 62.6% +/- 3.3% in the zero flow, low flow and hypoxic groups, respectively, vs 31.0 +/- 3.0% in controls (all P < 0.05). In hearts subjected to acidosis there was no protection (recovery of cardiac output 38.1 +/- 2.7%). Impairment of oxygen delivery appears to be the principle component of ischaemia responsible for the induction of preconditioning. Metabolite accumulation appears to play no significant role.