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