The effect of body temperature on myocardial protection conferred by ischaemic preconditioning or the selective adenosine A(1) receptor agonist GR79236, in an anaesthetized rabbit model of myocardial ischaemia and reperfusion

1 The cardioprotective effect of N-[(1S, trans)-2-hydroxycyclopentyl]adenos ine (GR79236), an adenosine A, receptor agonist, was compared with that pro duced by ischaemic preconditioning in an anaesthetized rabbit model of myoc ardial ischaemia and reperfusion. In addition, we examined the effect of di fferent body core temperatures on GR79236- or ischaemic preconditioning-ind uced cardioprotection when administered prior to ischaemia, and on cardiopr otection induced by GR79236 administered 10 min prior to the onset of reper fusion. 2 When rabbits were subjected to 30 min occlusion of the left coronary arte ry, followed by 2 h reperfusion, GR79236 (3 x 10(-8) mol kg(-1) i.v. (10.5 mu g kg(-1) i.v.)) or ischaemic preconditioning (5 min ischaemia followed b y 5 min reperfusion), administered or applied 10 min prior to the occlusion , significantly limited the development of infarction. The cardioprotective effect of ischaemic preconditioning was significantly greater than that se en after administration of GR79236. Pre-treatment with the selective adenos ine A, receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 3.3 x 10(-6) mol kg(-1) (1 mg kg(-1) i.v.)), prevented the cardioprotective effe ct of GR79236, but not that of ischaemic preconditioning. 3 Maintaining body core temperature at 38.5 degrees C rather than at 37.0 d egrees C did not influence infarct size in control groups of rabbits, but r educed the cardioprotective effect of GR79236 when administered 10 min prio r to occl usion or 10 min prior to the onset of reperfusion, The cardioprot ective effec t of ischaemic preconditioning was not temperature-dependent. 4 In conclusion, myocardial protection conferred by GR79236 in anaesthetize d rabbits is mediated via adenosine A, receptors. Myocardial protection can be conferred when GR79236 is administered before the onset of ischaemia or reperfusion, and is reduced when body core temperature is maintained at 38 .5 degrees C rather than at 37.0 degrees C. In contrast, myocardial protect ion conferred b y ischaemic preconditioning is not reduced by adenosine A, receptor blockade, or by maintaining body core temperature at 38.5 degrees C rather than at 37. 0 degrees C. These findings point to distinct differen ces in the mechanisms of induction of myocardial protection by adenosine A, receptor agonist and i schaemic preconditioning. They also highlight the n eed for careful control o f body core temperature when investigating the ph enomenon of cardioprotectio n.