Biomedical Engineering Reference
In-Depth Information
build-up of excess tissue levels of hypoxanthine. When oxygen is reintroduced
during reperfusion, conversion of the excess hypoxanthine by xanthine oxidase
results in the formation of toxic reactive oxygen species (ROS). In addition to
causing direct cell injury, ROS increase leukocyte activation, chemotaxis, and
leukocyte-endothelial adherence at er HR (Carden
et al.
2000, Collard
et al.
2001).
h e ischaemia produces expression of certain pro-inl ammatory gene products
such as cytokines, endothelial, neutrophil and platelets adhesion molecules. h is
helps in recruitment of neutrophil at the ischaemic tissue. h e ini ltration of
neutrophil in ischaemic area cause further release of pro-inl ammatory cytokines
and enhance tissue damage. h us, ischaemia induces pro-inl ammatory state in
tissue and increases tissue vulnerability to further damage when oxygen supply is
restored. h is type of tissue insult, unfortunately, is not restricted to local tissue.
If severe enough, it can cause damage to distant organs and leads into systemic
inl ammatory response syndrome (Ley 1991, Bevilacqa 1993).
ROLE OF ENDOTHELIUM-NEUTROPHIL INTERACTION
h e ischaemia promotes expression of certain pro-inl ammatory gene products
(e.g., adhesion molecules, cytokines) and bioactive agents (endothelium
thromboxane) on the endothelium. h us, ishcaemic insult makes the tissue
vulnerable to further injury.
Following ischaemia reperfusion-induced leukocyte activation, leukocytes and
endothelium interact in a series of distinct steps characterized by leukocyte rolling
on the endothelium and i rm adherence of leukocytes to the endothelium and
endothelial transmigration.
Within the endothelium, ischaemia promotes the expression of pro-
inl ammatory gene products (e.g., leukocyte adhesion molecules) and bioactive
agents (e.g., endothelin, thromboxane A2), while repressing other 'protective' gene
products (e.g., constitutive nitric oxide synthase, thrombomodulin) and bioactive
agents (e.g. prostacyclin, nitric oxide). h us, ischaemia induces a pro-inl ammatory
state that increases tissue vulnerability to further injury on reperfusion (Bevilacqua
1993, Watson 1998).
h e recruitment of neutrophil at the site of injury is an initial important step
in pathophysiology of HR injury. Following tissue inl ammation and trauma,
a portion of the rolling leukocytes are observed to l atten and spread on the
endothelium and then to stick i rmly. Some of the adherent leukocytes crawl
over the endothelial surface, seeming to probe for an opening and then diapedes
(crawl) between endothelial cells. Once in the extravascular tissue, the extravasated
leukocytes continue to migrate toward the inl ammatory site. In the last decade,
in vitro
and
in vivo
studies have identii ed many of the adhesion molecules on
neutrophil and endothelium, and locally generated inl ammatory mediators that
are involved in the adhesive interaction.
