The accumulation of
adenosine during a brief
coronary occlusion has been proposed to mediate the
infarct size-limiting effect of ischemic preconditioning. The purpose of this study was to compare the effects of ischemic preconditioning and a transient
adenosine infusion on myocardial interstitial fluid (ISF)
adenosine levels and
infarct size. Microdialysis fibers (10.0 mm length) were placed in the left ventricular myocardium of
pentobarbital sodium-anesthetized rabbits to estimate ISF
adenosine. Ischemic preconditioning was induced by 5 min of coronary artery occlusion and 10 min of reperfusion before 45 min of occlusion.
Adenosine preconditioning was induced with 5 min of intravenous
adenosine infusion (140 micrograms.kg-1.min-1) followed by a 10-min washout before the prolonged occlusion.
Myocardial infarct size was determined by
triphenyltetrazolium chloride staining after 3 h of reperfusion. Five minutes of
ischemia and 5 min of
adenosine infusion produced comparable increases in
dialysate adenosine levels (from 0.19 +/- 0.02 to 0.69 +/0- 0.11 and 0.28 +/- 0.10 to 0.71 +/- 0.18 microM, respectively) that decreased to baseline before the prolonged
ischemia; however, ischemic-preconditioned hearts exhibited elevated
dialysate adenosine levels for the first 5 min of reperfusion. Ischemic-preconditioned hearts exhibited significantly reduced
dialysate adenosine concentrations for the first 20 min of the prolonged occlusion (P < 0.05 vs. control), and
infarct size was reduced from 41 +/- 6 to 10 +/- 4% of risk area.
Adenosine preconditioning had no effect on
dialysate adenosine levels during prolonged
ischemia but did reduce
infarct size to 25 +/- 5% of risk area. These results indicate that a transient increase in ISF
adenosine can reduce
myocardial infarct size, but
adenosine alone does not fully replicate the protective effects of ischemic preconditioning.