title: Enhancement of reperfusion injury by elevation of microvascular pressures.
abstract: Elevated venous pressure can be associated with severe tissue injury. Few links, however, between venous hypertension and tissue damage have been established. We examined here the effects of micropressure elevation on the outcome of venular occlusion/reperfusion in the mesenteric microvasculature of male Wistar rats. One hour of venular occlusion (diameter approximately 50 microm) by micropipette occlusion followed by reperfusion were carried out with sham surgery without occlusion as control. Leukocyte rolling, adhesion, and migration, oxygen radicals detected by dichlorofluorescein (DCF), and parenchymal cell death detected by propidium iodide (PI) were recorded simultaneously in the same vessel at a location upstream of the occlusion site with elevated micropressure and at a downstream location with low micropressure. The number of rolling, adhering, and migrating leukocytes increased on the upstream side of the occlusion to a higher level than downstream of the occlusion site. During occlusion, DCF intensity on the venular endothelium was greater on the upstream side than in the downstream side, but there were no differences during reperfusion. The number of PI-positive cells adjacent to the venules increased significantly compared with controls, and it remained greater on the upstream higher-pressure side than the downstream side. Leukocyte adhesion and transvascular migration in postcapillary venules as well as parenchymal cell death could be significantly reduced by the hydroxyl radical scavenger dimethylthiourea. Microhemorrhages of blood cells into the mesentery interstitium were observed only on the upstream side of the occlusion. These results indicate that an elevation of the venular blood pressure during occlusion/reperfusion exacerbates the inflammatory cascade and tissue injury. Venous occlusion may constitute an important mechanism for tissue injury.
authors.affiliation: Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California-San Diego, La Jolla, California 92093-0412, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takase
authors.forename: Laurence
authors.initials: L
authors.lastname: Lerond
authors.forename: John J
authors.initials: JJ
authors.lastname: Bergan
authors.forename: Geert W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006439:Hemodynamics / Q000502:physiology*; D006470:Hemorrhage / Q000473:pathology; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000502:physiology; D014661:Vasoconstriction; D014699:Venules / Q000473:pathology / Q000503:physiopathology
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; C037631:2',7'-dichlorofluorescein