**5. Histology of arterial grafts**

[27-32] Ischemic insult and decreased production of nitric oxide and adenosine may cause SMC proliferation. [33] As it has been demonstrated that intimal hyperplasia does not occur in vein-to-vein isografts, it can be stated that pathologic changes seen in SVG in the arterial circulation are predominantly caused by hemodynamic and physiochemical

SVG failure can be divided into three temporal categories: early (0 to 30 days), midterm (30 days to 1 year) or late (after 1 year). Early SVG failure due to thrombotic complica‐ tions is mainly attributable to technical errors during harvesting, anastomosis or com‐ prised anatomic runoff. [19,35-37] It occurs in 15% to 18% of VG during the 1st month. [38-40] Early thrombotic complications in SVG in the arterial circulation are caused by a reduction of tissue plasminogen activator, attenuation of thrombomudulin and reduced

Midterm SVG failure is mainly caused by fibrointimal hyperplasia as it serves as the founda‐ tion for subsequent graft atheroma leading to occlusive stenosis. The release of a variety of mediators, growth factors, and cytokines by the injured endothelium, platelets and activated macrophages will cause migration and proliferation of SMC. Diminished production of endothelial nitric oxide (NO), prostaglandin 12 and adenosine will further contribute to and enhanced SMC proliferation, leading to development of neointimal hyperplasia. [19,33,37,42-44] Changes in the flow pattern within the vessel (shear stress) an ischemic insults may contribute to changes in the SVG at this stage. SVG are exposed to much higher mechanical pressure that they were adapted to (arterial versus venous blood pressure) which can poten‐ tially stimulate SMC proliferation. Moreover, after encountering arterial flow patterns increased levels of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemotactic protein-1 will facilitate leukocyte-endothelial interactions so that leukocyte infiltration of the lesions will ensue. [34] Finally, the adaptive response to hemody‐ namic factors, i.e. wall shear stress, may affect the distal site of the anastomosis leading to SVG failure. [45,46] Midterm SVG failure accounts for an additional 15% to 30%. [47,48] In the course of vessel remodelling, late SVG failure is characterized by progression of intimal fibrosis at the cost of a reduction in cellularity which may contribute to progression of SMC apoptosis. [19,34,41,44] In addition, perivascular fibroblasts may also be involved in neointimal formation and matrix deposition as these cells may exhibit contractile elements while migrating from the adventitia towards the media. [49] After 1 year most SVG stenosis is due to atherosclerosis but although vein graft atherosclerosis is accelerated compared to arteries, evidence show that a fully evolved plaque appear after 3 to 5 years of implantation. [35,47,50] In SVG there is no focal compensatory enlargement in the stenotic segments which is in contrast to native atherosclerotic arteries in which the development of an atherosclerotic plaque is associated with enlargement of the vessel and preservation of the lumen area until plaque progression exceeds the compensatory mechanism of the vessel. [51] Several studies show that SVG patency at 10 years is no more than 50% to 60%. [19,41,52,53] Finally, several studies have suggested a role of immune cells in neointimal formation as macrophages are found in the intima, while T-lymphocytes are present in the adventitia of neointimal lesions wit a predom‐

changes. [34]

196 Artery Bypass

expression of heparin sulphate. [41]

inance of CD4+ cells. [54-56]

Several arterial conduits are suitable for myocardial revascularization and the arterial conduits can be divided into 3 types according to functional class (Table 1). Type I arterial grafts are the somatic arteries including the IMA, IEA, and subscapular artery. Type II arterial grafts are the splanchnic arteries including the GEA, splenic artery, and inferior mesenteric artery. Type III arterial grafts are the limb arteries including the RA, ulnar artery, and lateral femoral circum‐ flex artery. Compared to functional class type II and III, type I is less spastic. [61] Although the full length of arterial grafts is reactive, the major muscular components are located at the two ends of the artery (muscular regulator). [62] Therefore, in terms of preventing vasospasm of arterial grafts, trimming off the small and highly reactive distal end of the grafts (IMA, GEA, IEA, or other grafts) may be important and clinically feasible.

Studies have demonstrated that there are differences between arterial and venous grafts: 1) arterial grafts are less susceptible to vasoactive substances then veins [63]; 2) the arterial wall


grafted, the 10 year LIMA patency to the LAD is reported to be 96% and to the circumflex (Cx) 89%. [72] The early patency of the RIMA anastomosed to major branches of the left circumflex artery is approximately 94%. [70] The mean RIMA patency at 5 years is reported to be 96%, at 10 years it is 81% and at 15 years it is 65%. [71] Again differences are observed, the RIMA graft patency to the LAD artery is 95% at 10 years and 90% at 15 years. Ten-year RIMA patency to the Cx marginal is 91%, right coronary artery is 84%, and posterior descending artery is 86%. [72] In situ RITA and free RITA had similar ten-year patency, 89% vs 91% respectively. RA patency is reported to range between 83% to 98% at 1 to 20 years but lower rates have been reported. [73] The patency rate estimated by the Kaplan-Meier method for the GEA conduit was 96.6% at 1 month, 91.4% at 1 year, 80.5% at 5 years, and 62.5% at 10 years. [74] Arterial grafts are not uniform in their biological characteristics and difference in the perioperative behaviour and in the long-term patency may be related to different characteristics. It should be taken into account in the use of arterial grafts that some grafts need more active pharma‐

Treatment of Coronary Artery Bypass Graft Failure

http://dx.doi.org/10.5772/54928

199

cological intervention during and after operation to obtain satisfactory results.

by surgical manipulation. Type II vasoconstrictor is 5-hydroxytryptamine.

grafting target arteries with a stenosis less than 90% with RA grafts. [81]

graft. Age may be of influence the quality of the arterial graft.

Although, the IMA is the most used conduit to restore the blood flow to the LAD, it is less easy to use because of its complicated preparation and postoperative complications. Specific reasons for not to use the RIMA may include additional time to harvest, concerns over deep sternal wound infection, myocardial hypoperfusion, and unfamiliarity. Besides the potentially deleterious effect on the vascular supply of the forearm and hand, potential spasm and size matching to target coronary artery are the main drawback for the use of RA in CABG. [75,76]

Although all arterial grafts may develop vasospasm, it develops more frequently in the GEA and RA, than the IMA and IEA. [13,77] Two types of vasoconstrictors are found to be important spasmogens in arterial grafts. [78] Type I vasoconstrictors are the most potent and they strongly contracts arterial grafts even when the endothelium is intact. The constrictors are endothelin, prostanoids such as thromboxane A2 and prostaglandin F2α, and alpha1-adrenoceptor agonists. Type II vasoconstrictors induce only weak vasoconstriction when the endothelium is intact, but play an important role in the spasm of arterial grafts when the endothelium is destroyed

Early IMA graft failure is attributed to technical errors and distal anastomosis. [79,80] Non‐ technical factors that may affect the patency of the arterial graft are high levels of LDL cholesterol and triglycerides, and high levels of lipoprotein(a), a thrombogenic molecule that is related to the hypercoagulable state. Other classical risk factors for coronary artery disease, such as diabetes mellitus, smoking and hypertension may also affect the patency of the arterial

Furthermore, competitive flow and low-flow profoundly affect graft patency. Low-grade graft stenoses in the target artery proximally are a major cause of competitive flow which may lead to a decrease in antegrade flow in the arterial graft causing early failure ('disuse athrophy'). The SVG and IMA are more tolerant than the RA and GEA conduits. This is likely to be related to biological differences as the RA and GEA have a thick layer of smooth muscle or poor endothelial function in these muscular conduits. Therefore, it is recommended to avoid

**Table 1.** Functional classification of arterial grafts according to physiological and pharmacological contractility, anatomical, and embryological characteristic

is supplied by the vaso vasorum and in addition through the lumen, whereas the veins are only supplied by the vaso vasorum [64]; 3) the endothelium of the arteries may secrete more endothelium-derived relaxing factor [65]; 4) the structure of the artery is subject to high pressure, whereas the vein is subjected to low pressure. While the SVG have to adapt to the high pressure, the arterial grafts do not which may partly explain the difference in the longterm outcome.

Similar like SVG, the arterial grafts can also be divided into three layers: the intima, media, and adventitia. As a result of location at different parts of the body and supply to different organs, differences in gross anatomy among arterial grafts have been observed. Divergent anatomic structures of the arteries have been observed. One of the most obvious differences is that arteries such as the GEA, IEA, and RA contain more smooth muscle cells in their walls and are therefore less elastic compared to other arteries such as the IMA which may be more elastic because they contain more elastic laminae. [64] Such structure divergence may also explain the difference in phsysiologic and pharmacologic reactivity.
