DOES INTERSTITIAL ADENOSINE MEDIATE ACUTE HIBERNATION OF GUINEA-PIG MYOCARDIUM

Objective: The aim was to test the role of interstitial adenosine in p rotective downregulation of myocardial energy demand during myocardial hibernation. Methods: Isolated working guinea pig hearts, perfused wi th glucose fortified Krebs-Henseleit, were subjected to 60 min global low flow ischaemia followed by 30 min reperfusion. Left ventricular pe rformance was assessed from heart rate-developed pressure product and pressure-volume work. Cytosolic energy level was indexed by creatine p hosphate and ATP phosphorylation potentials measured in snap frozen my ocardium. Lactate and purine nucleosides (adenosine, inosine) were mea sured in venous effluent. Results: When coronary flow was lowered by 8 0% for 60 min, heart rate-pressure product and pressure-volume work fe ll 87% and 75%, respectively, and stabilised at these low levels, but fully recovered when flow was restored. Myocardial ATP phosphorylation potential fell by 67% during the first 10 min of ischaemia, but subse quently recovered to preischaemic levels despite continuing ischaemia, indicating downregulation of myocardial energy demand. Lactate releas e increased about 10-fold during ischaemia and remained increased unti l reperfusion. Purine nucleoside release varied reciprocally with phos phorylation potential, peaking at 10 min of ischaemia, then gradually returning to the preischaemic level during the subsequent 50 min of is chaemia. The ecto 5'-nucleotidase inhibitor alpha,beta-methylene adeno sine 5'-diphosphonate (50 mu M) decreased ischaemic purine nucleoside release by 41%, but did not attenuate postischaemic contractile recove ry. The unspecific adenosine receptor antagonist 8-p-sulphophenyl theo phylline (8-SPT, 20 mu M) doubled ischaemic lactate release and lowere d coronary venous purine nucleoside release by 21%. 8-SPT increased ph osphorylation potential at 10 min ischaemia relative to untreated hear ts, but blunted the subsequent rebound of phosphorylation potential. 8 -SPT treatment during ischaemia resulted in a significantly higher cyt osolic phosphorylation potential at 30 min of reperfusion, but did not affect postischaemic contractile function. Conclusions: We conclude t hat activation of adenosine receptors results in recovery of cytosolic energy level of moderately Ischaemic working myocardium, but this ene rgetic recovery is not solely responsible for postischaemic contractil e recovery.