The time course of cardioprotection induced by GR79236, a selective adenosine A(1)-receptor agonist, in myocardial ischaemia-reperfusion injury in the pig

The cardioprotective effects of the selective adenosine A(1)-receptor agoni st, GR79236 (N-[(1S, trans)-2-hydroxycyclopentyl]adenosine), were examined in a porcine model of myocardial ischaemia-reperfusion injury. When pigs we re subjected to a 50-min coronary artery occlusion followed by 3-h reperfus ion, GR79236 (10 nmol/kg, i.v.) significantly reduced infarct size whether given 10 min before the onset of ischaemia or reperfusion. This effect was independent of the bradycardia induced by GR79236, as it was also observed in animals in which heart rate was maintained by electrical pacing. However , GR79236 administered 10 min after reperfusion did not reduce infarct size . GR79236 had no effect on the incidence or outcome of ventricular dysrhyth mias in this pig model of infarction. Similarly, ischaemic preconditioning (IPC, 2 x 10-min ischaemia and 10-min reperfusion) significantly reduced in farct size. The selective adenosine Al-receptor antagonist, 8-cyclopentyl-1 ,3-dipropylxanthine (DPCPX; 3.3 mu mol/kg, i.v.), abolished the haemodynami c and cardioprotective effects of GR79236 and the cardioprotective effects of IPC in anaesthetised pigs. In conclusion, GR79236 exerted a marked cardi oprotective effect in a porcine model of myocardial ischaemia-reperfusion i njury, provided that it was administered before reperfusion. This suggests that GR79236 may have clinical utility in the treatment of various aspects of ischaemic heart disease.