Sunday, December 18, 2016
Monday, December 5, 2016
How a venous/coronary artery bypass graft fails ? (What is neointimal hyperplasia ) ?
The main limitation of coronary artery bypass
grafting (CABG), when the saphenous vein is used as
a conduit, is poor long-term vein graft patency. Fiveyear
failure rates are 30–50% and have remained unchanged
despite rapid development of pharmacological
treatments and technologies.
Perhaps the most important change following vein grafting is the exposure of saphenous vein to the arterial circulation. In the venous circulation saphenous vein is subjected to low pressure, non-pulsatile flow and a shear stress of around 0.2 dyne/cm2
Following grafting the vein is exposed to high pressure, pulsatile flow and a shear stress of approximately 3-6 dynes/cm 2. In addition to increased shear stress the vein is subjected to a variety of other new haemodynamic forces, including radial and circumferential deformation.
The another main reason for vein graft occlusion, especially in the mid-term, is neointimal hyperplasia (NIH).
Following vein grafting there is rapid deposition of leukocytes, platelets and other blood components. . These accumulating cells and blood components may have an important influence on the later development of intimal hyperptasia.In the experimental situation inhibiting leukocyte accumulation using an antibody to CD4 results in a reduction in the development of intimal hyperplasia,
while reduction in platelet aggregation using an antibody to GP IIb-IIIa has been shown to reduce the incidence of restenosis following coronary angioplasty in vivo.
Monocytes is also playing important role. Studies of excised vein graft stenoses has demonstrated an abundance of proliferating monocytes and macrophages in the intima of these lesions.
Leukocytes can release cytokines, oxygen-derived free radicals and lysosomal proteinases, which, by direct effects on smooth muscle cells and also modulation of endothelial products, e.g. inactivation of nitric oxide, may influence smooth muscle cell proliferation and migration.
Similarly deposited platelets release smooth muscle mitogens, such as platelet derived growth factor, which encourage smooth muscle cell proliferation and migration into the intima.
Studies in cultured cells have demonstrated that haemodynamic forces have an important influence on the endothelial expression of molecules controlling leukocyte and platelet adhesion. Thus it is tempting to explain the association between haemodynamic forces and vein graft thickening by their effect on the accumulation of blood elements.
It is well-known that aortocoronary grafts fashioned from internal mammary artery or radial artery are much more durable than saphenous vein grafts and it is of note that SMCs derived from internal mammary artery proliferate less than SMCs from saphenous vein.
There are significantly higher activity of phosphatase and tensin homolog (PTEN) in the smooth muscle cells of the internal mammary artery than in the saphenous vein.
In summary one can say that :
In vein-graft failure various factors pathophysiologiclly are involved , including PTEN, matrix metalloproteinases, and tissue inhibitor of metalloproteinases, in uncontrolled proliferation and migration of smooth muscle cells towards the lumen, and invasion of the graft conduit.
Perhaps the most important change following vein grafting is the exposure of saphenous vein to the arterial circulation. In the venous circulation saphenous vein is subjected to low pressure, non-pulsatile flow and a shear stress of around 0.2 dyne/cm2
Following grafting the vein is exposed to high pressure, pulsatile flow and a shear stress of approximately 3-6 dynes/cm 2. In addition to increased shear stress the vein is subjected to a variety of other new haemodynamic forces, including radial and circumferential deformation.
The another main reason for vein graft occlusion, especially in the mid-term, is neointimal hyperplasia (NIH).
Following vein grafting there is rapid deposition of leukocytes, platelets and other blood components. . These accumulating cells and blood components may have an important influence on the later development of intimal hyperptasia.In the experimental situation inhibiting leukocyte accumulation using an antibody to CD4 results in a reduction in the development of intimal hyperplasia,
while reduction in platelet aggregation using an antibody to GP IIb-IIIa has been shown to reduce the incidence of restenosis following coronary angioplasty in vivo.
Monocytes is also playing important role. Studies of excised vein graft stenoses has demonstrated an abundance of proliferating monocytes and macrophages in the intima of these lesions.
Leukocytes can release cytokines, oxygen-derived free radicals and lysosomal proteinases, which, by direct effects on smooth muscle cells and also modulation of endothelial products, e.g. inactivation of nitric oxide, may influence smooth muscle cell proliferation and migration.
Similarly deposited platelets release smooth muscle mitogens, such as platelet derived growth factor, which encourage smooth muscle cell proliferation and migration into the intima.
Studies in cultured cells have demonstrated that haemodynamic forces have an important influence on the endothelial expression of molecules controlling leukocyte and platelet adhesion. Thus it is tempting to explain the association between haemodynamic forces and vein graft thickening by their effect on the accumulation of blood elements.
It is well-known that aortocoronary grafts fashioned from internal mammary artery or radial artery are much more durable than saphenous vein grafts and it is of note that SMCs derived from internal mammary artery proliferate less than SMCs from saphenous vein.
There are significantly higher activity of phosphatase and tensin homolog (PTEN) in the smooth muscle cells of the internal mammary artery than in the saphenous vein.
In summary one can say that :
In vein-graft failure various factors pathophysiologiclly are involved , including PTEN, matrix metalloproteinases, and tissue inhibitor of metalloproteinases, in uncontrolled proliferation and migration of smooth muscle cells towards the lumen, and invasion of the graft conduit.
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