In medicine, vein graft failure (VGF) is a condition in which

vein Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...

grafts Grafting refers to a surgical procedure to move tissue from one site to another on the body, or from another creature, without bringing its own blood supply with it. Instead, a new blood supply grows in after it is placed. A similar technique ...

, which are used as alternative conduits in bypass surgeries (e.g. CABG), get occluded. Veins, mainly the

great saphenous vein The great saphenous vein (GSV, alternately "long saphenous vein"; ) is a large, subcutaneous, superficial vein of the leg. It is the longest vein in the body, running along the length of the lower limb, returning blood from the foot, leg and thig ...

(GSV) are the most frequently used conduits in bypass surgeries ( CABG or PABG), due to their ease of use and availability. Some structural changes of

intima The tunica intima (New Latin "inner coat"), or intima for short, is the innermost tunica (layer) of an artery or vein. It is made up of one layer of endothelial cells and is supported by an internal elastic lamina. The endothelial cells are in ...

thickening and vein wall remodeling are necessary for vein graft adaptation to the arterial environment. The reasons why some of the grafts progress to clinical

stenosis A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture). ''Stricture'' ...

is unknown. The patency rates of saphenous vein grafts after CABG at 1 year is approximately 80%. After 5 years the patency rate drops to 65% and at 10 years GSV patency rates are approximately 50%, with only half of the veins are

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

free. VGF may be identified in

asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...

patients, but can also produce symptoms of

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

, depending on the area of the supplied territory of the heart, and the function of native arteries and other grafts. VGF has been closely correlated with

revascularization In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of reva ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

and

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

. Treatment of occluded GSVs can be performed by

percutaneous coronary intervention Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the ...

or redo CABG and is considered to be challenging, and thus preventing their obstruction is of great importance.

Mechanism

During and after the harvesting, veins go through a period of

and reperfusion after engraftment, which causes damage to endothelial and

smooth muscle cells Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

(SMC). The grafting exposes the vein to arterial pressure and flow that causes increased

shear stress Shear stress, often denoted by (Greek: tau), is the component of stress coplanar with a material cross section. It arises from the shear force, the component of force vector parallel to the material cross section. ''Normal stress'', on the ot ...

and wall tension, which further damages the endothelial layer and SMC. The damage causes local release of

tissue factor Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the ''F3'' gene, present in subendothelial tissue and leukocytes. Its role in the clotting process is the initiation of thrombin formation from the ...

s and reduced

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...

and

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

(NO), all of which contribute to

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

activation, deposition of

fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...

, which promotes

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...

Growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...

that released from

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

and platelets lead to increased proliferation and

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

of SMCs to the intima. The migrated SMC release

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

resulting in reduced intimal cellularity. Low levels of endothelial nitric oxide,

adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...

and

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

, further contribute to SMC proliferation. Over time continued SMC migration and proliferation cause extracellular matrix deposition and fibrotic change that lead to development of intimal hyperplasia, which results in luminal loss that makes the graft more susceptible to atherosclerosis. Progressive atherosclerosis is the primarily cause of late vein graft failure. Vein graft atherosclerotic lesions are more diffuse and concentric, yet less calcified, compared to native atherosclerotic lesions, and are more susceptible to thrombosis formation and rupture.

Graft failure depending on saphenous vein harvesting technique

Having an intact outer fat pedicle is what differentiates the two main techniques for harvesting saphenous vein grafts. Conventionally, the outer fat pedicle is removed during the harvesting process. It has been proposed that the no-touch technique, leaving the outer fat pedicle intact, will cause less endothelial damage at the time of harvest. This lessens intimal hyperplasia in the long run.

Prevention

Statins Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...

and

antiplatelets An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effecti ...

such as

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

, are the only medications recommended by the ESC guidelines and the ACC/AHA Task Force guidelines for the prevention of VGF. Different surgical techniques had been studied in attempt to reduce VGF. The No-touch technique is where the vein is harvested with the surrounding tissues, keeping the

vasa vasorum Vasa vasorum are small blood vessels that comprise a vascular network supplying the walls of large blood vessels, such as elastic arteries (e.g., the aorta) and large veins (e.g., the venae cavae). The name derives . Occasionally two different ...

and the nerves in the

adventitia The adventitia () is the outer layer of fibrous connective tissue surrounding an organ. The outer layer of connective tissue that surrounds an artery, or vein – the tunica externa, is also called the ''tunica adventitia''. To some degree, its ...

intact. This technique shown to improve vein graft patency and less development of intimal hyperplasia. Despite the benefits shown, the use of No-touch technique in CABG is limited to a few centers. Probably because of the shift toward improved cosmetic outcome and ''patient satisfaction'' provided by endoscopic vein harvesting (EVH). Although, EVH has been associated with higher risk of vein graft stenosis and occlusion. The solutions in which vein grafts are stored after harvesting also play an important role. Buffered saline, instead of saline or

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

, has shown to reduce the risk of significant stenosis or occlusion. Providing the vein with external support prior to grafting has shown to reduce intimal hyperplasia formation and improve the hemodynamics within the graft.

Gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

is another strategy that been suggested to prevent VGF as the veins are ideally suited for ''

ex vivo ''Ex vivo'' (Latin: "out of the living") literally means that which takes place outside an organism. In science, ''ex vivo'' refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal ...

'' treatment prior to grafting.

Preclinical studies In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...

showed that such strategy has the potential to reduce intimal hyperplasia but more clinical data is needed.

References

{{reflist Veins Surgery