Adenosine A3 pretreatment before cardioplegic arrest attenuates postischemic cardiac dysfunction.
BACKGROUND
The cardioprotective effects of the adenosine A3 receptor in a cardioplegia model have not been described. We tested the hypothesis that infusion of the A3 receptor agonist, Cl-IB-MECA (100 nM), as a pretreatment (PTx) and/or as a cardioplegic (CP) additive reduces postischemic myocardial 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 (A3-PTx), (3) no PTx and Cl-IB-MECA CP (A3-CP), or (4) Cl-IB-MECA PTx and Cl-IB-MECA CP (A3-[PTx+CP]).


RESULTS
Coronary flow was not increased after A3 pretreatment when compared to baseline values. After 2 hours of reperfusion, left ventricular developed pressure in control and A3-CP groups was depressed to 43% +/- 3% and 47% +/- 2% of baseline; while A3-PTx and A3-[PTx+CP] significantly increased left ventricular developed pressure (65% +/- 3% and 61% +/- 5%) from baseline relative to control and A3-CP. Effluent creatine kinase activity was significantly decreased by A3-PTx (1520 +/- 32 IU/L), A3-[PTx+CP] (1481 +/- 41 IU/L) from control (1734 +/- 54 IU/L) and A3-CP (1750 +/- 43 IU/L). Myocardial edema (% tissue water) was significantly less in A3-PTx (78 +/- 0.6%) and A3-[PTx+CP] (76% +/- 2%) compared with control (85% +/- 0.4%) and A3-CP (83% +/- 2%).


CONCLUSIONS
Adenosine A3 receptor stimulation as a pretreatment attenuates postischemic cardiodynamic dysfunction and creatine kinase release but has no cardioprotection as an adjunct to cold cardioplegia.
Thourani
V H
VH
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Ronson
R S
RS
Jordan
J E
JE
Guyton
R A
RA
Vinten-Johansen
J
J
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D005069:Evaluation Studies as Topic; D006324:Heart Arrest, Induced; D019157:Ischemic Preconditioning, Myocardial; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D058906:Purinergic P1 Receptor Agonists; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left
D058906:Purinergic P1 Receptor Agonists; D003402:Creatine Kinase; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide