Myocardial adenosine does not correlate with the protection mediated by ischaemic or pharmacological preconditioning in rat heart.

1. We tested the hypothesis that ischaemic preconditioning of the rat heart activates cardiovascular adenosine formation to provide enhanced cardioprotection. 2. Rat isolated perfused hearts were either non-preconditioned, preconditioned with 5 min ischaemia or treated for 5 min with the alpha1-adrenoceptor agonist phenylephrine (50 micro mol/L) before being subjected to 30 min sustained ischaemia followed by 30 min reperfusion. Isolated cardiomyocytes were either non-preconditioned, subjected to 10 min simulated ischaemia or treated for 10 min with phenylephrine (50 micro mol/L) before being subjected to 30 min simulated ischaemia. Functional recovery of hearts and cell viability were used as indices of the effects of ischaemia. 3. Myocardial adenosine, as well as intracellular pH, was determined at the end of the preconditioning period and at 10, 20 and 30 min of sustained ischaemia. Intracellular pH was also determined during the reperfusion. 4. Ischaemic or pharmacological preconditioning with phenylephrine correlated with an improved functional recovery of perfused hearts during reperfusion and increased cell viability during ischaemia. 5. In perfused hearts, ischaemic preconditioning resulted in increased adenosine production in the myocardium during the following sustained ischaemia. However, in isolated cardiomyocytes, adenosine levels during sustained ischaemia were lower in ischaemically preconditioned cells compared with the respective non-preconditioned cardiomyocytes. 6. The increase in adenosine production was not observed in hearts preconditioned with phenylephrine instead of transient ischaemia. Similarly, pharmacological preconditioning resulted in decreased adenosine levels during sustained ischaemia in isolated cardiomyocytes. 7. Intracellular pH was preserved during ischaemia to the same extent in both ischaemically or pharmacologically preconditioned hearts and cardiomyocytes, indicating that less acidosis during ischaemia is related to protection. 8. Taken together, the results suggest that cardioprotection does not necessarily correlate with increased adenosine production. Thus, adenosine concentration is not crucial to the beneficial effects of preconditioning in rat heart.