Previously, we have demonstrated the role of
nucleoside transport and
purine release in post-ischemic
reperfusion injury (myocardial stunning) in several canine models of
ischemia. Since rabbits are deficient of
xanthine oxidase, it is not known whether selective blockade of
purine release is beneficial in a rabbit model of coronary artery occlusion and reperfusion (stunning). Therefore, we determined the hemodynamic and metabolic correlates in response to
myocardial stunning in the presence or absence of selective
nucleoside transport blocker (p-nitrobenzylthioinosine,
NBMPR) and
adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine, EHNA). Sixty adult anaesthetized rabbits were surgically prepared for hemodynamic measurements. After stabilization period, the left anterior descending coronary artery was occluded for 15 min and reperfused for 30 min. Transmural myocardial biopsies were obtained from the ischemic LAD area and from the non-ischemic posterior (circumflex, CFX) segment of the myocardium. Rabbits (n = 60) were randomly assigned to either the control or the
EHNA/
NBMPR-treated group (
n = 30 each). Each group was further divided to either functional or metabolic groups (n = 15 each subgroup). Each animal received intravenously 30 ml of either a vehicle
solution or 100 M
EHNA and 25 M
NBMPR 10 min before
ischemia. Although administration of
EHNA/
NBMPR did not affect the heart rate, it did cause mild
hypotension (about 20-30%). Fifteen minutes of LAD occlusion resulted in significant
ATP depletion and concomitant accumulation of
nucleosides in both groups (p < 0.05 vs. baseline and non-ischemic CFX segment).
AMP was higher in the LAD compared to the CFX segment. Significant accumulation of
adenosine was observed in the treated group compared to the control group. It is concluded that
EHNA/
NBMPR induced site specific entrapment of
adenosine of
nucleoside transport in the rabbit heart, in vivo.