EFFECTS OF ISCHEMIA, PRECONDITIONING, AND ADENOSINE-DEAMINASE INHIBITION ON INTERSTITIAL ADENOSINE LEVELS AND INFARCT SIZE

In order to examine the relationship between local adenosine concentra tions before, during, and after ischemia and the extent of ischemic my ocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60' coronary artery oc clusion (CAO) and 3 h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inos ine and hypoxanthine), myocardial infarct size, and myocardial blood f low (MBF) were determined in control animals (n = 6), animals precondi tioned with a single 10' cycle of CAO and REP (PC, n = 6), and those t reated with the adenosine deaminase inhibitor pentostatin (n = 6, 0.2 mg/Kg IV 30' prior to CAO). The brief PC occlusion resulted in a trans ient but significant increase in dialysate ADO (6.7 +/- 1.8 mu M vs. 0 .67 +/- 0.1 mu M at baseline). Pentostatin administration had no signi ficant effect on either dialysate nucleosides or MBF at baseline. Duri ng the 60' CAO, diary sate ADO increased in control animals. In PC ani mals, however, dialysate ADO during CAO was lower than control. Pretre atment with pentostatin resulted in a six-fold augmentation in dialysa te ADO during the 60 min CAO when compared to the control values (110. 62 +/- 30.2 mu M vs. 16.31 +/- 2.1 mu M at 60 min of ischemia). Pentos tatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating deaminase activity. There were no significant differences in MBF between groups at any time point. Foll owing 3 h REP, infarct size was 35.4 +/- 5.5 %, 8.1 +/- 1.5 % and 8.3 +/- 1.8 % of the region at risk in control, PC, and pentostatin groups , respectively. These data suggest that marked increase in ISF ADO dur ing CAO, may be as effective in reducing INF as a modest increase in I SF ADO prior to prolonged CAO.