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.

Recent studies suggest that inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A (HMB-CoA) reductase exert a protective effect against endothelial dysfunction. Nevertheless, there are no data regarding their use as cardioprotective agents in acute myocardial ischemia. The aim of the present study was to evaluate, in isolated working hearts of normolipidemic rats. the effects of simvastastin (S) against myocardial reperfusion injury. Isolated working 18 rat hearts were subjected to 15 min. global ischemia and 60 min, reperfusion. We valued functional parameters, CPK release, heart weight changes. microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. S was added to perfusion buffer (modifed Krebs-Henseleit solution) at IO mu M. 25 mu M, 50 mu M and 100 mu M concentrations. In 35 mu M S-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CPK release, myocardial edema and FITC-albumin extravasation. This cardioprotection was less evident in 50 mu M S-treated hearts. In 100 mu M S group endothelial and myocytic damage significantly increased and a proarrhythmic effect was detected. Data were confirmed by ultrastructural morphometry that revealed a reduction of endothelial lesions and myocytic damage only in 25 and 50 mu M S-treated hearts. Our data point out that acute S administration may reduce I/R injury in isolated working rat hearts.

Recent studies suggest that Al adenosine receptor antagonists may prevent reperfusion injury. The pathophysiology of this protective effect is unclear, a possible involvement of inhibition of superoxide anion release from neutrophils, leukocyte activation and platelet aggregation it's reported. We tested the hypothesis of a blood-independent cardioprotection following Al adenosine receptor antagonism with DPCPX (1,3 dipropyl,8-cyclopentylxanthine). Isolated working rat hearts were used and submitted to 10 and 30 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. We evidenced that At 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 interstitium and improvement of coronary microcirculation.