Adenosine A(3) pretreatment before cardioplegic arrest attenuates postischemic cardiac dysfunction

Background. The cardioprotective effects of the adenosine A(3) receptor in a cardioplegia model have not been described. We tested the hypothesis that infusion of the A(3) receptor agonist, Cl-IB-MECA (100 nM), as a pretreatm ent (PTx) and/or as a cardioplegic (CP) additive reduces postischemic myoca rdial injury. Methods. Isolated perfused rat hearts underwent 30 minutes of normothermic ischemia, 60 minutes of intermittent hypothermic cardioplegia (10 degrees C ), followed by 2 hours of reperfusion. Hearts were divided into four groups : (1) no pretreatment (PTx) and unsupplemented cardioplegia (CP) (control), (2) Cl-IB-MECA PTx and unsupplemented CP (A(3)-PTx), (3) no PTx and Cl-IB- MECA CP (A(3)-CP), or (4) Cl-IB-MECA PTx and Cl-IB-MECA CP (A(3)-[PTx+CP]). Results. Coronary now was not increased after A(3) pretreatment when compar ed to baseline values. After 2 hours of reperfusion, left ventricular devel oped pressure in control and A(3)-CP groups was depressed to 43% +/- 3% and 47% +/- 2% of baseline; while A(3)-PTx and A(3)-[PTx+CP] significantly inc reased left ventricular developed pressure (65% +/- 3% and 61% +/- 5%) from baseline relative to control and A(3)-CP. Effluent creatine kinase activit y was significantly decreased by A(3)-PTx (1520 +/- 32 IU/L), A(3)-[PTx+CP] (1481 +/- 41 IU/L) from control (1734 +/- 54 IU/L) and A(3)-CP (1750 +/- 4 3 IU/L). Myocardial edema (% tissue water) was significantly less in A(3)-P Tx (78 +/- 0.6%) and A(3)-[PTx+CP] (76% +/- 2%) compared with control (85% +/- 0.4%) and A(3)-CP (83% +/- 2%). Conclusions. Adenosine A(3) receptor stimulation as a pretreatment attenuat es postischemic cardiodynamic dysfunction and creatine kinase release but h as no cardioprotection as an adjunct to cold cardioplegia. (C) 1999 by The Society of Thoracic Surgeons.