Microvascular in vivo assessment of reperfusion injury: significance of prostaglandin E 1 and I 2 in postischemic “no-reflow” and “reflow-paradox”

Abstract

Background Microvascular ischemia-reperfusion (I/R) injury is characterized by failure of capillary perfusion (“no-reflow”) and reoxygenation-associated phenomena (“reflow-paradox”), including activation of leukocyte-endothelium interaction with cytotoxic mediator-induced loss of endothelial integrity. The objectives of this study were to elucidate the impact of both prostaglandins E 1 (PGE 1) and I 2 (PGI 2) in microvascular reperfusion injury, with special focus on the distinct pathophysiology of no-reflow- and reflow-paradox phenomena. Materials and methods By use of the hamster dorsal skinfold preparation and in vivo fluorescence microscopy, the microcirculation of a striated skin muscle was assessed before 4 h of pressure-induced ischemia and 0.5, 2, and 24 h after onset of reperfusion. Results I/R was characterized by enhanced leukocyte-endothelium interaction in postcapillary venules, increase of macromolecular leakage, and reduction of functional capillary perfusion ( P < 0.05). Intravenous 2-h infusion of PGE 1, starting with onset of reperfusion, reduced leukocyte adhesion and macromolecular leakage in postcapillary venules during early reperfusion ( P < 0.05), while 6-h infusion, given during ischemia and early reperfusion, showed no significant effects. PGI 2 infusion also attenuated postischemic leukocyte adhesion, which was significant by a 6-h prolonged administration ( P < 0.05), but did not influence the increase of microvascular permeability. Both prostaglandins were unable to prevent the postischemic failure of capillary perfusion (no-reflow). Conclusions Both prostaglandins did not significantly influence postischemic no-reflow phenomena, but appeared as potent inhibitors of reflow-paradox under the experimental circumstances of this study.