Microvascular oxygenation and oxidative stress during postischemic reperfusion. PO2, ROS, and NO during reperfusion.
Increased formation of ROS on reperfusion after ischemia underlies ischemia reperfusion (I/R) damage. We measured, in real time, both oxygen tension in microvessels and tissue and oxidant stress during postischemic reperfusion in hamster cheek pouch microcirculation. We measured PO2 by using phosphorescence quenching microscopy and oxygen radical species (ROS) production in the systemic blood. We evaluated the effects of a NOS inhibitor (L-NMMA) and superoxide dismutase (SOD) on the oxidative stress during reperfusion. Microvascular injury was assessed by measuring diameter change, the perfused capillary length (PCL), and leukocyte adhesion. Our findings demonstrate that early reperfusion is characterized by low concentration of oxygen linked to increased production of ROS. After this initial transience in arterioles, the oxygen tension and production of ROS return to normal after reperfusion, while the blood flow and capillary perfusion decrease. The early increased ROS production, in turn, may impair oxygen consumption by endothelial cells, thus further promoting activation of oxygen to ROS. This event is substantiated by the finding that treatment with SOD maintains ROS at normal levels, which, in turn, should be effective to increase the production of endothelial NO. Conversely, a decrease in NO levels led to decreased ROS production during early reperfusion, which increased later during reperfusion, ultimately causing vasoconstriction and greatly increasing venular leukocyte adhesion on postcapillary venules during hypoxic conditions. Therefore, low-flow hypoxia is primarily responsible for vascular endothelial damage during reperfusion through changes in ROS and NO production.
Bertuglia
Silvia
S
Giusti
Andrea
A
D000818:Animals; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood*; D017382:Reactive Oxygen Species / Q000097:blood; D015427:Reperfusion Injury / Q000097:blood*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D010100:Oxygen