Effects of A1 adenosine receptor antagonism against ischaemia-reperfusion damage and coronary microcirculation in isolated working rat hearts

Journal of Clinical and Basic Cardiology 1999; 2 (1): 99-104

PDF    Summary    Figures   




Keywords: Adenosinrezeptor,  DPCPX,  Endothel,  isoliertes Herz,  Mikrozirkulation,  Reperfusionsschaden,  adenosine receptors,  DPCPX,  endothelium,  microcirculation,  reperfusion damage,  working heart

Previous studies suggest that A1 adenosine receptor antagonists may prevent myocardial reperfusion injury by means of an inhibition of superoxide anion release from neutrophils, leukocyte activation and platelet aggregation. We tested the hypothesis of a blood-independent endothelial protection following A1 adenosine receptor antagonism with DPCPX (1,3 dipropyl,8-cyclopentylxanthine) during ischeamia-reperfusion damage. Isolated working rat hearts were used and submitted to 10 and 20 min global ischaemia in order to assess functional alterations, necrosis enzyme and purine release in coronary effluent, arrhythmias, heart weight changes, ultrastructural morphometry and microvascular permeability by FITC-albumin diffusion technique. DPCPX (100 mM) was administered to perfusion buffer before ischaemia. In untreated hearts we detected a significant reduction of functional parameters, associated with a significant enzyme and purine release, myocardial oedema and ultrastructural damage. In DPCPX-treated hearts functional and histological damage was significantly reduced compared to controls. Moreover, a significant reduction of postischaemic endothelial hyperpermeability (FITC-albumin diffusion, p < 0.02) and ultrastructural damage was observed. Our data suggest that A1 adenosine receptor antagonism significantly reduces ischaemia-reperfusion damage in isolated, crystalloid perfused rat hearts by direct reduction of endothelial damage and postischaemic hyperpermeability. J Clin Basic Cardiol 1999; 2: 99-104.