Postischemic cardiac function recovery in the isolated rat heart: effects of adenosine deaminase and nucleoside transport inhibition

Background and aims: This study assessed the cardioprotective effects of in hibitors of adenosine metabolism in an isolated perfused rat heart model. S pecifically, we studied the adenosine deaminase inhibitor erythro-9-(2-hydr oxy-3-nonyl)adenine and the selective nucleoside transport inhibitor 6-(p-n itrobenzyl)-6-thioinosine, in terms of their potential to enhance protectio n when added to Bretschneider's cardioplegic solution. Methods: Rat hearts were infused for 5 min with Krebs-Henseleit buffer solution (,group 1), Bre tschneider's cardioplegic solution (group 2), Bretschneider's cardioplegic solution with the addition of 25 CIM erythro-9-(2-hydroxy3-nonyl)-adenine a nd 5 muM S-(p-nitrobenzyl)-6 -thioinosine (group 3), and Bretschneider's ca rdioplegic solution with the addtion of 25 I-IM erythro-9-(2-hydroxy-3-nony l)-adenine only (group 4). After cardioplegic arrest and 45 min of ischemic storage at 25 degreesC, the functional recovery of the hearts was tested d uring 15 min of Langendorff reperfusion and then 45 min of working heart re perfusion. Results: In relation to the cardioprotective effects of Bretschn eider's cardioplegic solution alone, we observed an improved recovery of he modynamic function of the hearts with the addition of both erythro-9- (2-hy droxy-3-nonyl)adenine and S-(p-nitrobenzyl)-6-thioinosine. However, the myo cardial adenosine triphosphate (ATP) concentration remained unchanged. Brad ycardia observed under the addition of erythro-9-(2-hydroxy3-nonyl)-adenine alone was prevented by the addition of S-(p-nitrobenzyl)-6-thioinosine. Co nclusion: A combination of both substances may be tested further for cardia c preservation, as it might improve the recovery from ischemia at moderate temperatures.