Different effects of an adenosine A1 analogue and ischemic preconditioning in isolated rabbit hearts.
BACKGROUND
Ischemic preconditioning reduces infarct size, but its effects on postischemic function are variable. Adenosine, which is thought to play a role in ischemic preconditioning, reduces both infarct size and postischemic dysfunction. The purpose of this study was to compare the cardioprotective effects of ischemic preconditioning and an adenosine A1 receptor agonist on recovery of function and infarct size in isolated rabbit hearts.


METHODS
Krebs buffer-perfused hearts (at least 7 per group) were subjected to 60 minutes of global ischemia (37 degrees C) and 60 minutes of reperfusion. Ventricular function was assessed by measuring left ventricular developed pressure, and infarct size (percentage of the left ventricle) was determined by tetrazolium staining.


RESULTS
Control hearts exhibited 34% +/- 6% infarct size and 56% +/- 4% recovery of preischemic left ventricular developed pressure. Ischemic preconditioning reduced infarct size to 13% +/- 1% but had no effect on recovery of function (65% +/- 5%). Hearts treated with the adenosine A1 agonist R-phenylisopropyladenosine for 5 minutes immediately before ischemia exhibited both reduced infarct size (10% +/- 2%) and enhanced postischemic recovery of left ventricular developed pressure (86% +/- 3%). Termination of the R-phenylisopropyladenosine treatment before ischemia eliminated its beneficial effects. The adenosine A1 receptor antagonist DPCPX blocked both of the effects of R-phenylisopropyladenosine but did not block ischemic preconditioning.


CONCLUSIONS
These results demonstrate fundamental differences between the cardioprotective effects of adenosine A1 receptor activation and ischemic preconditioning.
Lasley
R D
RD
Department of Surgery, University of Wisconsin School of Medicine, Madison 53792-0001, USA.
Noble
M A
MA
Konyn
P J
PJ
Mentzer
R M
RM
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D016277:Ventricular Function, Left; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D010660:Phenylisopropyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine