Pre-conditioning activates adenosine utilization in a cost-effective way during myocardial ischaemia

During pre-conditioning the interstitial concentration of adenosine, in con trast to lactate, presents a die-away curve-pattern for every successive ep isode of ischaemia. This die-away pattern might not necessarily be attribut ed to diminished adenosine production. The present study was undertaken to Investigate whether pre-conditioning alters the metabolic turnover of adeno sine as observed by the lactate production during ischaemia. Interstitial l evels of metabolites In pre-conditioned (n = 21) and non-preconditioned (n = 21) porcine hearts were monitored with microdialysis probes Inserted in b oth Ischaemic and non-ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buf fer containing adenosine (375 muM), or buffer containing deoxyadenosine (37 5 muM) were studied. All animals were subjected to 90 min of equilibrium mi crodialysis before 40 min of regional myocardial Ischaemia and 120 min of r eperfusion. Pre-conditioning consisted of four repetitive episodes of 10 mi n of ischaemia and 20 min of reperfusion. Significantly higher levels of In osine and lactate were found in the ischaemic tissue of the pre-conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgro ups receiving deoxyadenosine and plain buffer, respectively. This differenc e was only valid for pre-conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non-preconditioned Isch aemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non-ischaemic myocardium baseline levels of metabolites were measur ed in all subgroups. Pre-conditioning favoured degradation of exogenous ade nosine to Inosine successively ending up In enhanced lactate production. Th is was probably because of the involvement of the hexose monophosphate path way in the pre-conditioned ischaemic myocardium. This route may therefore b e supplementary In energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (A TP) investment. Utilization of adenosine in this way may also explain the s uccessive die-away pattern of adenosine seen in consecutive pre-conditionin g cycles.