ADENOSINE BLOCKADE DURING REPERFUSION REVERSES THE INFARCT LIMITING EFFECT IN PRECONDITIONED CANINE HEARTS

Objectives: The aim was to investigate whether adenosine release after reperfusion contributes to infarct limitation by ischaemic preconditi oning. Methods: Dogs underwent preconditioning with four 5 min cycles of left anterior descending coronary artery (LAD) occlusion and reperf usion, followed by 90 min LAD occlusion and 5 h reperfusion with or wi thout the non-specific adenosine receptor blocker, 8-phenyltheophyllin e (8-PT). Infarct size was assessed by a dual staining method with tri phenyltetrazolium chloride and Evans blue. Blood flow measurements in the subendocardial region were made by infusion of coloured microspher es before occlusion and midway through the sustained occlusion. Transc ardiac alteration of neutrophillic function was assessed by luminol-en hanced whole blood chemiluminescence induced by zymosan. Results: Infa rct size was significantly reduced in the preconditioned dogs [12.5(SE M 4.0)%, n = 10, p < 0.01] compared with the control dogs [40.5(6.1)%, n = 10], an effect significantly reduced by the 8-PT treatment [23.4( 4.9)%, n = 8]. Treatment with 8-PT without ischaemic preconditioning h ad no effect on infarct size [42.8(6.3)%, n = 7]. There was no differe nce in myocardial blood flow in the ischaemic or non-ischaemic subendo cardial tissue between any pair of the four groups. The ratio of whole blood chemiluminescence in the cardiac vein to that in the carotid ar tery was considerably reduced in preconditioned dogs compared with tha t in control dogs after reperfusion. Myeloperoxidase activity in the i schaemic myocardium and the peripheral neutrophil count at the end of the experiment were both also decreased compared with control dogs. In preconditioned dogs treated with 8-PT, neutrophillic function in the coronary circulation after reperfusion was increased compared with tha t in both controls and preconditioned dogs with no 8-PT treatment. The re was no difference in neutrophillic function between the 8-PT-treate d dogs with or without ischaemic preconditioning. Treatment with 8-PT increased myeloperoxidase activity in the ischaemic myocardium of the preconditioned dogs, and no difference was seen in activity between do gs treated with 8-PT with or without ischaemic preconditioning. Conclu sions: An adenosine receptor blocker caused a moderate but significant reversal of infarct limitation by ischaemic preconditioning associate d with a significant increase of neutrophillic function in the coronar y circulation during early reperfusion.