Intermittent adenosine at the beginning of reperfusion does not trigger cardioprotection.
BACKGROUND
Postconditioning (PostC) maneuvers allow post-ischemic accumulation of autacoids, which may trigger protection. Intermittent infusion of either bradykinin or diazoxide during early reperfusion triggered PostC protection via redox signaling. Here we tested whether intermittent adenosine (ADO) may trigger PostC-like cardioprotection.


METHODS
Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. PostC (5 cycles of 10-s reperfusion/ischemia) or short-term ADO treatment were performed immediately after the 30 min ischemia. Non-selective ADO receptor-antagonist (8-SPT) was infused during PostC maneuvers. Left ventricular pressure was monitored, and infarct size was evaluated by using nitro-blue-tetrazolium staining.


RESULTS
In Control hearts after ischemia/reperfusion, infarct size was 64% +/- 4% of risk-area. PostC reduced infarct size to 28% +/- 3% (P < 0.01). PostC protection was abolished by 3 min of the infusion of 8-SPT during PostC maneuvers. Since 3 min of ADO infusion (1 mum or 30 mum) did not trigger PostC protection, protocol with intermittent ADO infusion (5 cycles of 10-s buffer-no-ADO/buffer-plus-ADO) was used to mimic PostC. Also intermittent ADO did not attenuate infarct size (75% +/- 2%; P = NS versus ADO and Control; P < 0.01 versus PostC). Despite disparities on infarct size, post-ischemic systolic function was similar among groups.


CONCLUSIONS
Data suggest a strong ADO-dependent anti-infarct effect, but no an anti-stunning effect, by ischemic PostC. Neither intermittent ADO nor 3 min continuous ADO can trigger protection against infarct size extension. Yet, 3 min ADO antagonist can prevent PostC protection. It is thus likely that endogenous ADO binding with receptors during early reperfusion is necessary, but nonsufficient to induce protection against infarct size extension.
Penna
Claudia
C
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Mancardi
Daniele
D
Tullio
Francesca
F
Pagliaro
Pasquale
P
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage*
D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine