Enhancement of reperfusion injury by elevation of microvascular pressures

Abstract

-Schö nbein. Enhancement of reperfusion injury by elevation of microvascular pressures. Am J Physiol Heart Circ Physiol 282: H1387-H1394, 2002; 10.1152/ajpheart.01003.2000.-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 ϳ50 m) 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. rat mesentery; venules; free radicals; cell death; leukocytes; endothelium; propidium iodide; 2Ј,4Ј-dichlorodihydrofluorescein; venous hypertension; microhemorrhage PRIMARY AND SECONDARY VENOUS INSUFFICIENCY is characterized by destruction of venous valves and elevation of venous pressure. Under chronic conditions of venous pressure elevation, a number of indicators of inflammation can be detected (7, 23), including endothelial adhesion molecule expression (22), release of proteolytic enzymes (26), and the presence of leukocyte migration into valve tissue and the venous wall (19,25). The trigger mechanisms that lead to development of the inflammatory reaction in venules with leukocyte and endothelial activation remain incompletely defined.There is now a large body of evidence to suggest that temporary arterial occlusion followed by reperfusion leads to an inflammatory cascade with cell activation and injury (for a recent review, see Ref. 3). Mainly, such studies have been carried out with occlusi...

Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension

“…All the above observations were made at sites upstream of the occlusion, subjected to both reduced flow (to near zero) and increased pressure. In order to distinguish between the effects of these two factors, in a subsequent series of experiments, 13 upstream sites were compared with sites downstream of the occlusion (which experienced only the reduction in flow). The number of leukocytes rolling and adhering during reperfusion, the number migrating into the interstitial space, and the amount of parenchymal cell death were all elevated at both sites, and the kinetics of the changes were similar.…”

Chronic Venous Insufficiency and the Therapeutic Effects of Daflon 500 mg

“…In our model of venous occlusion and re-perfusion, the number of rolling, adherent, and migrating leukocytes increased as did the number of apoptotic cells in the parenchyma. 23 In Daflon 500 mg-treated animals, these cardinal markers of inflammation were decreased in a dose-dependent manner. 24 Taken together, the effects of Daflon 500 mg on the microcirculation in these animal models suggests that it might be useful clinically to decrease the effects of chronic venous insufficiency.…”

Hypertension

“…Except in specialized microvascular beds, such as the renal glomerulus, normal systemic capillary pressure (here, we disregard the pulmonary circulation, which is not relevant to the field of systemic hypertension) is relatively low (10 to 30 mm Hg). 11 Elevation of systemic capillary pressure above this range has several potentially deleterious effects, including the following: (1) interstial edema, which can have dramatic effects on the brain as exemplified in hypertensive encephalopathy 12 ; (2) disruption of capillary wall structure, with extravasation of plasma proteins and blood cells 13 ; and (3) activation of the microvascular endothelium, which may trigger or amplify an inflammatory cascade, 14 of importance, for example, in the pathogenesis of venous ulcers. 15 Pleiotropic changes in the functional behavior of arterioles have been noted in both clinical and experimental hypertension, including hyperresponsiveness to vasoconstrictor stimuli, 16,17 leading to their constriction or even complete closure, 16,18,19 endothelial dysfunction, 20,21 and reduced bioactivity of endothelium-derived NO.…”