Adenosine blockade during reperfusion reverses the infarct limiting effect in preconditioned canine hearts

Abstract

The aim was to investigate whether adenosine release after reperfusion contributes to infarct limitation by ischaemic preconditioning. Dogs underwent preconditioning with four 5 min cycles of left anterior descending coronary artery (LAD) occlusion and reperfusion, followed by 90 min LAD occlusion and 5 h reperfusion with or without the non-specific adenosine receptor blocker, 8-phenyltheophylline (8-PT). Infarct size was assessed by a dual staining method with triphenyltetrazolium chloride and Evans blue. Blood flow measurements in the subendocardial region were made by infusion of coloured microspheres before occlusion and midway through the sustained occlusion. Transcardiac alteration of neutrophillic function was assessed by luminol-enhanced whole blood chemiluminescence induced by zymosan. Infarct size was significantly reduced in the preconditioned dogs [12.5(SEM 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 had no effect on infarct size [42.8(6.3)%, n = 7]. There was no difference in myocardial blood flow in the ischaemic or non-ischaemic subendocardial tissue between any pair of the four groups. The ratio of whole blood chemiluminescence in the cardiac vein to that in the carotid artery was considerably reduced in preconditioned dogs compared with that in control dogs after reperfusion. Myeloperoxidase activity in the ischaemic 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 that in both controls and preconditioned dogs with no 8-PT treatment. There was no difference in neutrophillic function between the 8-PT-treated 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 dogs treated with 8-PT with or without ischaemic preconditioning. An adenosine receptor blocker caused a moderate but significant reversal of infarct limitation by ischaemic preconditioning associated with a significant increase of neutrophillic function in the coronary circulation during early reperfusion.