Recent studies suggest that A1
adenosine receptor antagonists may prevent
reperfusion injury in the lung and heart. The pathophysiology of this protective effect is unclear; a possible inhibition of
superoxide anion release from neutrophils, or leukocyte activation and platelet aggregation are reported. We tested the hypothesis of a blood-independent cardioprotection following A1
adenosine receptor antagonism with 1,3 dipropyl,8-cyclopentylxanthine (
DPCPX). Isolated working rat hearts were submitted to 10 and 20 min global
ischemia in order to assess functional alterations,
necrosis enzyme and
purine release in coronary effluent, arrhythmias, heart weight, ultrastructural morphometry and microvascular permeability by
FITC-albumin diffusion technique.
DPCPX (100 nM) was administered to the perfusion
buffer before
ischemia. In untreated hearts we detected a significant impairment of function, associated with a significant
enzyme and
purine release, myocardial
edema and ultrastructural damage. In
DPCPX-treated hearts functional and histological damage was significantly reduced compared to controls. Moreover, a significant reduction in postischemic endothelial permeability (
FITC-albumin diffusion, p < 0.02) and ultrastructural damage was observed. Our data suggest that A1
adenosine receptor antagonism with
DPCPX significantly reduces
ischemia-
reperfusion damage in isolated,
crystalloid perfused rat heart by a direct reduction of endothelium damage, fluid diffusion within the interstitium and improvement of coronary microcirculation.