Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning

We used mice with genetic disruption of the A(3) adenosine receptor (AR) gene (A(3)AR(-/-) mice) to assess the in vivo role of the A(3)AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A(3)AR(-/-) compared to wild-type mice (A(3)AR(+/+)), The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A(1)ARs. However, neutrophil infiltration within infarcted regions was less in A(3)AR(-/-) mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A(3)AR(-/-) and A(3)AR(+/+) mice. These results indicate that, in the mouse, (i) A(3)ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A(3)ARs are not necessary for the development of the early phase of ischemic PC. (C) 2001 Academic Press.