[Effect of A1 adenosine receptor blockade on postischemic damage to the coronary microcirculation].
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.
Di Napoli
P
P
Dipartimento di Cardiologia e Cardiochirurgia, Università degli Studi G D'Annunzio, Chieti.
Di Crecchio
A
A
Taccardi
A A
AA
Di Muzio
M
M
Statile
D
D
Maggi
A
A
Giuliani
P
P
Di Iorio
P
P
Barsotti
A
A
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D008833:Microcirculation / Q000187:drug effects*; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects*
D018047:Receptors, Purinergic P1; D000241:Adenosine
Effetti del blocco dei recettori A1 dell'adenosina sul danno postischemico della microcircolazione coronarica.