SUPPRESSION OF THE DEGRADATION OF ADENINE-NUCLEOTIDES DURING ISCHEMIAMAY NOT BE A SUFFICIENT MECHANISM FOR INFARCT SIZE LIMITATION BY PRECONDITIONING

Preconditioning is known to decelerate degradation of the tissue adeni ne nucleotides during ischemia and to delay ischemic myocardial necros is. However, it is not known whether these two phenomena are related. To obtain an insight into this question, the present study examined wh ether adenosine and B2 receptor antagonists, which block the infarct s ize-limiting effect of preconditioning, modify the interstitial purine levels during preconditioning and subsequent sustained ischemia. In p entobarbital anesthetized open-chest rabbits, a microdialysis probe wa s placed in the territory of a branch of the left coronary artery, and perfused with Ringer solution. Preconditioning was performed with 5 m in ischemia/5 min reperfusion. Dialysate adenosine and inosine were el evated from the baseline values of 0.064 +/- 0.011 and 0.329 +/- 0.044 mu M to 0.189 +/- 0.069 and 4.106 +/- 1.451 mu M, respectively during preconditioning, but their elevation during a subsequent 20 min of is chemia was significantly lower compared with that in the non-precondit ioned myocardium. This suppression of the purine accumulation during i schemia by preconditioning was not abolished by 2 mu g/kg of Hoe 140, a specific B2 receptor antagonist, or by 10 mg/kg of 8-phenyltheophyll ine, a non-selective adenosine receptor antagonist. Since the doses of Hoe 140 and S-phenyltheophylline are sufficient to block the infarct size-limiting effect of preconditioning, the present results suggest t hat there is a dissociation between the suppression of adenine nucleot ide degradation during ischemia by preconditioning and the enhancement of myocardial resistance against infarction. Thus, it is unlikely tha t a reduction of adenine nucleotide utilization by preconditioning is sufficient to protect the myocardium against ischemic necrosis.