MODULATION OF ENDOTHELIAL FUNCTION IN VASCULAR GRAFTS

Project: Research project

Project Details

Description

The proposed studies will examine the function of the endothelium
in biological and synthetic vascular grafts. In vitro techniques
used to study endothelium-dependent responses in arteries and veins
will be used to determine the functional state of the intima of
autografts, allografts and of the neointima of synthetic vascular
&rafts. A key question is whether the endothelium of veins
implanted into the arterial circulation (vein grafts) produce and
release factors in addition to metabolites of arachidonic acid
which can modulate the tone of the underlying smooth muscle and act
synergistically with prostacyclin to inhibit platelet aggregation.
These experiments will identify the presence of chemical substances
which could limit or promote thrombus formation, an important
factor in limiting patency in vascular grafts. Other studies are
designed to examine differences in the production and release of
endothelium-derived factors in vein grafts implanted in the reverse
and nonreverse (in situ) position and between vein grafts exposed
chronically to low and high blood flows. These studies will
identify physical factors which could alter endothelial function
and therefore the patency of the grafts. It will be determined
whether changes in responses of the vein grafts result from altered
function of the endothelium or of the smooth muscle. By using
selective inhibitors of receptors and enzymatic pathways, the
mechanism of action of endothelium-derived factors will be
determined. Similar studies will be performed on cryopreserved
veins before and after implantation into the arterial circulation.
Changes in endothelial function will be correlated with platelet
adhesion to the cryopreserved allografts sequentially following
implantation. The ability of the neointima of synthetic grafts to
release endothelium-derived substance other than prostacyclin will
be determined. The effectiveness of these substances to inhibit
platelet aggregation will be compared between grafts seeded with
endothelial cells of venous or arterial origin. It is anticipated
that these experiments will identify particular deficits in the
function of endothelial cells of vascular grafts which could lead
to selected therapy to improve graft patency. They will provide
new information crucial to understanding mechanisms associated with
thrombus formation in and occlusion of vascular grafts.
StatusFinished
Effective start/end date4/1/893/31/94

ASJC

  • Medicine(all)