Postischemic cardiac function recovery in the isolated rat heart: effects of adenosine deaminase and nucleoside transport inhibition.
OBJECTIVE
This study assessed the cardioprotective effects of inhibitors of adenosine metabolism in an isolated perfused rat heart model. Specifically, we studied the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine and the selective nucleoside transport inhibitor S-(p-nitrobenzyl)-6-thioinosine, in terms of their potential to enhance protection when added to Bretschneider's cardioplegic solution.


METHODS
Rat hearts were infused for 5 min with Krebs-Henseleit buffer solution (group 1), Bretschneider's cardioplegic solution (group 2), Bretschneider's cardioplegic solution with the addition of 25 microM erythro-9-(2-hydroxy-3-nonyl)-adenine and 5 microM S-(p-nitrobenzyl)-6-thioinosine (group 3), and Bretschneider's cardioplegic solution with the addtion of 25 microM erythro-9-(2-hydroxy-3-nonyl)-adenine only (group 4). After cardioplegic arrest and 45 min of ischemic storage at 25 degrees C, the functional recovery of the hearts was tested during 15 min of Langendorff reperfusion and then 45 min of working heart reperfusion.


RESULTS
In relation to the cardioprotective effects of Bretschneider's cardioplegic solution alone, we observed an improved recovery of hemodynamic function of the hearts with the addition of both erythro-9-(2-hydroxy-3-nonyl)-adenine and S-(p-nitrobenzyl)-6-thioinosine. However, the myocardial adenosine triphosphate (ATP) concentration remained unchanged. Bradycardia observed under the addition of erythro-9-(2-hydroxy-3-nonyl)-adenine alone was prevented by the addition of S-(p-nitrobenzyl)-6-thioinosine.


CONCLUSIONS
A combination of both substances may be tested further for cardiac preservation, as it might improve the recovery from ischemia at moderate temperatures.
Keeling
I M
IM
Department of Surgery, University Hospital, Graz, Austria. keelingi@medscape.com
Obermayr
R P
RP
Schneider
B
B
Spieckermann
P G
PG
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000378:metabolism*; D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D011343:Procaine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000345:Affinity Labels; C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D004791:Enzyme Inhibitors; D008353:Mannitol; D013868:Thioinosine; D011343:Procaine; C010192:9-(2-hydroxy-3-nonyl)adenine; D011189:Potassium Chloride; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D005947:Glucose; D000225:Adenine