The novel A(1)/A(2)
adenosine receptor agonist
AMP 579 has been reported to reduce
myocardial infarct size in pig and dog. The present study tested the effect of
AMP 579 in two rabbit models. In open-chest rabbits undergoing 30 min of regional
ischemia and 3 h of reperfusion
AMP 579 (3 microg/min/kg) reduced
infarct size when treatment was started either 10 min before
ischemia or 10 min prior to reperfusion from 36.4+/-3.1% of the risk zone in untreated hearts to 11.8+/-4.4 and 12.3+/-1.0%, respectively. To determine whether protection observed when the
drug was administered shortly before reperfusion represented a long-lasting effect rather than merely a transient delay of
necrosis, the chest
wound was closed in layers and the rabbits permitted to recover. After 3 days the hearts were removed to evaluate
infarct size. Continued limitation of
infarct size after 3 days of reperfusion (8.2+/-2.8% of the risk zone) confirmed that sustained tissue salvage had been conferred by the
drug. In isolated,
buffer-perfused rabbit hearts undergoing 30 min of regional
ischemia and 2 h of reperfusion,
AMP 579 again limited
infarct size (8.6+/-2.9% of the risk zone) when treatment started 10 min prior to reperfusion, arguing against an anti-leukocyte mechanism of protection.
AMP 579's protective effect in this in vitro model was abrogated by
8-(p-sulfophenyl)theophylline, indicating that it was mediated through
adenosine receptors. We conclude that
AMP 579 given just prior to reperfusion may be an effective anti-
infarct intervention.