Biomedical Engineering Reference
In-Depth Information
polyurethane. Furthermore, endothelial cell growth is stimulated in the presence
of the NO-releasing polyurethane, while smooth muscle cell growth is greatly
inhibited. The ability of this bioactive material to inhibit platelet adhesion and
smooth muscle cell proliferation while encouraging endothelialization suggests
that this NO-generating polyurethane may be suitable as a candidate material for
small-diameter vascular grafts. Early reendothelialization and inhibition of plate-
let aggregation should enhance long-term patency by establishing an endothelial
environment resembling that of normal healthy vessels. The endothelial cells that
overlie atherosclerotic plaques in diseased blood vessels do not produce much
biologically active NO because they express little eNOS. The therapeutic poten-
tial of NO-eluting polyurethane grafts may therefore lie in the hope that they
more closely mirror a healthy vascular endothelial phenotype (Verma and
Marsden
2005
).
The closely related topic of drug-eluting stents is described in detail in a special
report on cardiovascular drug delivery (Jain
2011b
). Nanotechnology has also been
incorporated into drug-eluting stents and is discussed in a report on nanobiotech-
nology (Jain
2011a
).
Carbon Monoxide Inhalation for Preventing Restenosis
Carbon monoxide (CO), a chemically stable gas, occurs in nature as a product of
the oxidation or combustion of organic materials. CO also arises in cells and tissues
as a byproduct of heme oxygenase (HO), a rate-limiting enzyme that degrades
heme into CO, iron, and bilirubin. CO acts as a vasorelaxant and may regulate other
vascular functions such as platelet aggregation and smooth muscle proliferation.
Many of the effects of CO depend on the activation of guanylate cyclase, which
generates guanosine 3¢,5¢-monophosphate (cGMP), and the modulation of mitogen-
activated protein kinase (MAPK) signaling pathways. Actions of CO on the human
body range from the physiological to the pathological: small amounts may be ben-
eficial but large amounts are toxic.
Veins are considered to be the best conduits available for CABG surgery. When
these arterialized vein grafts fail, it is often due to the development of intimal
hyperplasia. Ex vivo treatment of vein grafts in CO-saturated lactated Ringer solu-
tion has been shown to preserve vascular endothelial cell integrity perioperatively
and significantly reduces neointima formation (Nakao et al.
2010
). These effects
appear to be mediated through the activation of the HIF1a/VEGF pathway. CO is
an effective means of reducing intimal hyperplasia in large animals after vascular
injury when delivered during the operative procedure (Raman et al.
2006
). No
toxicity is associated with the increase in COHgb. The combination of CO and NO
provides additional protection against the vascular injury response, with a greater
reduction in neointima formation. These data suggest that these agents may prove
to be clinically beneficial in prolonging vascular patency after interventions.
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