ADENOSINE-DEAMINASE INHIBITION AUGMENTS INTERSTITIAL ADENOSINE BUT DOES NOT ATTENUATE MYOCARDIAL-INFARCTION

Objective: The objectives were to determine the effects of the adenosi ne deaminase inhibitor pentostatin (deoxycoformycin) on interstitial f luid (ISF) adenosine before, during, and after myocardial ischaemia an d to ascertain whether augmented endogenous ISF adenosine reduces myoc ardial infarction. Methods: Untreated anaesthetised dogs (n = 11) were compared to dogs treated with intravenous pentostatin 30 min before i schaemia (0.2 mg . kg(-1) n = 11). The changes in ISF adenosine, adeno sine metabolites, and lactate were assessed by cardiac microdialysis, using dialysate concentrations as indices of ISF levels. Both groups w ere exposed to 60 min of regional myocardial ischaemia followed by 3 h of reperfusion. Results: Although ISF adenosine increased during isch aemia in untreated animals, inosine and hypoxanthine were the predomin ant purine metabolites which accumulated in the ISE Pentostatin increa sed dialysate adenosine 3.5-fold before ischaemia, resulted in a susta ined and pronounced augmentation of adenosine during ischaemia, and ma intained the raised ISF adenosine during early reperfusion. However, t he augmentation of ISF adenosine was not associated with a reduction i n infarct size [untreated = 33.3(SEM 4.8)% of the area at risk; pentos tatin treated = 35.6(4.6)% of the area at risk], nor did pentostatin a lter the ischaemia induced increase in ISF lactate. Plasma adenosine, as measured by a microdialysis probe in the femoral artery, increased in pentostatin treated animals upon reperfusion, leading to systemic h ypotension, increased blood flow in the non-ischaemic region, and an a ttenuated reactive hyperaemia in the ischaemic region. Conclusions: Al though inhibition of adenosine deaminase effectively enhances ISF aden osine before and during ischaemia, the increase before ischaemia does not ''precondition'' the myocardium, nor does the augmentation of aden osine during and after ischaemia attenuate necrosis in this model of i schaemia. Therefore, the enhancement of ISF adenosine to the extent pr ovided by adenosine deaminase inhibition alone is not sufficient to pr otect the heart in the way seen with ischaemic preconditioning.