Polynitroxylated hemoglobin-based oxygen carrier: inhibition of free radical-induced microcirculatory dysfunction

Reactive oxygen species have been identified as key mediators of leukocyte/endothelial cell interaction under various pathological conditions and diseases such as ischemia/reperfusion injury, inflammation, and after exposure to cigarette smoke. Consequently, antioxidants have been shown to successfu...

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Bibliographic Details
Published in:Free radical biology & medicine 1999-07, Vol.27 (1), p.1-6
Main Authors: Saetzler, Rainer K, Arfors, Karl E, Tuma, Ron F, Vasthare, Usha, Ma, Li, Hsia, Carleton J.C, Lehr, Hans-Anton
Format: Article
Language:English
Subjects:
Animals
Antioxidant
Blood substitute
Cell Adhesion
Cigarette smoking
Cricetinae
Double-Blind Method
Endothelium, Vascular
Female
Free Radicals
Hemoglobins - metabolism
Leukocyte adhesion
Leukocytes - cytology
Leukocytes - physiology
Mesocricetus
Microcirculation
Oxygen - metabolism
Platelet aggregation
Smoking - adverse effects
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Summary:Reactive oxygen species have been identified as key mediators of leukocyte/endothelial cell interaction under various pathological conditions and diseases such as ischemia/reperfusion injury, inflammation, and after exposure to cigarette smoke. Consequently, antioxidants have been shown to successfully prevent the sequelae of these conditions, ranging from tissue infarction to atherogenesis. In this study we investigated whether, via its established superoxide dismutase-like activity, a novel polynitroxyl hemoglobin-based oxygen carrier (PNH), could affect the stimulation of leukocyte rolling and adhesion to endothelial cells in response to cigarette smoke. Using the dorsal skin fold chamber model for intravital microscopic observation of leukocyte/endothelium and −/platelet interactions in hamsters, we could demonstrate that cigarette smoke exposure elicited in control animals the rolling and adhesion of leukocytes along the endothelium of postcapillary venules and also of arterioles, as well as the formation of leukocyte/platelet aggregates. In contrast to the hemoglobin based oxygen carrier (HBOC) alone, that showed no therapeutic benefit, PNH significantly inhibited these proadhesive processes secondary to cigarette smoke. Also, PNH significantly reduced the formation of leukocyte/platelet aggregates in the blood stream of the cigarette smoke-exposed animals. These effects are not due to changes in microhemodynamic conditions, because wall shear rates remained unchanged in all three groups of animals.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(99)00037-4