The Influence Of PCI On The Human Body

Stent devices were invented in the 1980s and refined in the 1990s. Stenting techniques have transformed and expanded the therapeutic capabilities of angioplasty. There are two classification for stents based on their mode of deployment balloon-expandable and self-expandable. Stents are small mesh tubes which inserted to keep arteries open after angioplasty procedure. Drug -eluting stents have a polymer coating over mesh. This Polymer coatings have been proven to be durable and deliver drug in a uniform and controlled way ( White, Hollier 2007).

Many of the vaso-protective function of endothelium is provide by the Nitric Oxide(NO)20.Endothelium damaged by turbulent or non-laminar blood causes decreased production of NO.Such kind of blood flow also stimulates endothelial cells to produce adhesion molecules, which recruit and bind inflammatory cells. Hypercholesterolemia seems to inactivate the normal function of NO. The net effect is endothelial binding of monocytes and T cells, migration of these cells to the subendothelial space, and initiation of a local vascular inflammatory response. Lipids in the blood, particularly low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), also bind to endothelial cells. 18Firstly LDL is transported across the healthy intima and become trapped in intima of a vessel wall.It undergoes oxidative modification and then oxidized LDL(OxLDL) is formed5.OxLDL is mighty inducer of inflammatory molecules.It adds up to the inflamotory signaling by endothelium that activates chemotactic substances, growth factors that attracts monocytes to vessel wall21Eventually OxLDL transforms monocytes into macrophages which makes the Forms cells, which are the hallmark of atherosclerosis. Oxidized LDL impair the signal transduction between endothelial cell surface receptors and NO production, inhibit NO synthase activity and inactivates NO realese from endothelial cells.22.Once the endothelium is impaired, oxidized LDL is stored in vascular endothelium and by the process of series of mechanism, foam cells are formed and then eventually fatty plaque that occludes the vessel along with the decreased amount of NO which decreases the ability of the vessel to dilate. As the plaque grows arterial wall narrowing and thickening occurs5. This plaque and narrowing of vessel results in decreased blood flow

Cardiopulmonary bypass, CPB, is utilized in heart surgery when cardioplegia is required to perform a surgical intervention. CPB is associated with coagulopathy through the activation of the hemostatic system by different means. The direct contact with the CPB circuit is followed by a coagulation cascade through activation of factors.1,2 Simultaneously a stimulation of the fibrinolytic system3 and platelet activation4 occurs.

An atherothrombotic event result in infiltration of the vessel wall caused by high levels of fibrongen, increased blood viscosity, increased platelet aggregation and thrombus formation. A pivotal role is played by inflammation in all phases of atherosclerosis. There are several characteristics of atherosclerotic plaques including the expression of cellular adhesion molecules (CAM), blunted vascular reactivity, and a prothrombotic state. Recent studies suggest that in atherosclerotic plaques PPAR- gamma (Peroxisome proliferator activated receptor gamma) is highly expressed and dugs that mimic PPAR gamma may have inhibitory effects on inflammatory process resulting in improvement of endothelial dysfunction and can modify major transcription factor

Strategies to reduce bleeding have become an integral component of current PCI practice to decrease adverse outcomes 1,2. Bivalirudin, a direct thrombin inhibitor, has been demonstrated in multiple large-scale randomized trials to reduce major bleeding events after PCI among patients presenting with STEMI compared with UFH 3,8. However, bleeding reductions associated with bivalirudin therapy have occurred at the expense of increased rates of acute stent thrombosis 3,4,6,8. These trials have also varied in the proportion of use of glycoprotein IIb/IIIa-inhibitors (GPI) in the UFH arm, ranging from infrequent to moderate to obligatory 3-8. Given the association of GPI therapy with increased bleeding and reduced ischemia, it is nit clear whether observed differences between bivalirudin and UFH may be, at least in part, secondary to greater use of GPI therapy with UFH 9,10.

The endothelium consists of a dynamic organ system which maintains normal vessel homeostasis. It is a delicate layer of cells that clothes all blood vessels. The endothelium plays a major structural and functional role in the vascular health and in the initiation and development of cardiovascular diseases. Endothelium function regulates vasomotor tone, platelet aggregation, smooth muscle cell proliferation, monocyte and leucocyte adhesion and thrombosis. Therefore, endothelial dysfunction is an important process towards atherosclerotic disease and has been shown to be a predictor of cardiovascular events.

According to Shim, Siegel, Shim 2012, budgets are an efficient method of allocating financial resources to achieve strategic goals. For companies to compete in the global market it is essential to monitor and control spending in order to see progress toward reaching their goals. Budgets help to control spending, estimate cash flow and profits, while striving to meet goals.

Integrin Signaling in Endothelial Cell Activation. In quiescent vessels, the endothelial layer regulates vascular tone, provides an anti-thrombotic surface, and forms a tight barrier to restrict the passage of blood components into surrounding tissue [39]. Activation of the endothelial cell layer during inflammatory responses involves a phenotypic transition that increases vascular permeability and enhances the expression of leukocyte counter-receptors (e.g. ICAM-1, VCAM-1), proinflammatory cytokines (tumor necrosis factor α (TNFα), interleukin-1B (IL-1β)), and pro-coagulant molecules (tissue factor (TF)) [39]. Molecularly, endothelial activation represents the first discernable sign of local atherosclerotic susceptibility and is maintained during subsequent stages of atherosclerotic progression [40]. Several stimuli promote endothelial activation, including mechanical stress, oxidized LDL (oxLDL), proinflammatory cytokines (e.g. TNFα, IL-1β), and the bacterial endotoxin LPS [39]. Much of the reprogramming in endothelial gene expression can be attributed to the proinflammatory transcription factor nuclear factor-κB (NF-κB) [41, 42]. The NF-B family of homodimeric and heterodimeric transcription factors is maintained in an inactive state in the cytoplasm but translocates to the nucleus upon activation in response to a variety of endothelial cell activators

The main pathophysiologic mechanism of CMD is endothelial dysfunction with impaired vasodilatation, coagulation, inflammation, permeability, cell adhesion, and altered microvascular response. The

Common complications of PCI are bleeding, haematoma, and pseudoaneurysm to the access site. Some strategies such as using bivalirudin (thrombin-inhibitor), the radial approach and using proton pump inhibitors in patients on dual antiplatelet therapy who are at higher than average risk of gastrointestinal bleeds appear to reduce the risk of post-PCI bleeding. During the procedure, when the lumen diameter is widened, this is associated with major local trauma to the vessel wall so can, in turn, lead to complications in a minority of patients such as coronary perforation, dissection or rupture. Coronary perforation or rupture occurs in fewer than 1% of cases, making it very rare. Abrupt vessel closure may also occur, usually when the true lumen is compressed by a large dissection flap or thrombus formation, but the incidence of this has reduced significantly since the use of intracoronary stents and newer antiplatelet drugs. [18] Restenosis after PCI needing a second revascularization procedure is a major limitation, the rates of this have fallen to less than 10% with the introduction of DESs. Typically, it develops within 3-6 months and presents as a return of angina, it rarely causes MI. Stent thrombosis is a risk in 1-2% of patients, it is most frequent in the first month but can months or

784). The immune system attempts to attack the inflamed area in the artery with special white blood cells and “cells full of fatty nutrients, foam cells, begin to form there, too” (Sapolsky, 2004, p. 43). The white blood cells are unable to properly fight the affected area, and in turn, end up adding more substance to the build up. As this process continues, the affected area becomes inflamed and physically hardens. This produces a blockage in the artery and reduces blood flow, while also causing an increase in blood pressure. At this point of the atherosclerosis build up, many people, especially women, experience angina.

Coronary artery disease (CAD), also known as heart disease, is defined as the “narrowing or blockage of the arteries and vessels that provide oxygen and nutrients to the heart” (Milto, Odle, p.1). The main cause of CAD is an accumulation of fatty materials on the lining of arteries. Once the fatty materials line the inner arteries, it restricts blood flow to the heart. When blood is can no longer long flow to the heart, it causes a heart attack. Coronary artery disease is the leading cause of death in both women and men in the United States. The American Heart Association states that since 1990 deaths caused by the coronary artery disease have decreased, however, “more than 40,000 people still died from this disease in 2000” and about 13

The most feared pathophysiological effect of sepsis is the disturbance of the cardiovascular system through vasodilation and fluid loss from the vascular system into the tissue induced by elevated NO• concentrations. The successive drop in blood pressure and reduced supply of tissues leads to systemic circulatory failure and death of the patient. Inhibitor studies have shown that PARP-1 is not only involved in DNA repair, but also in septic shock. Hauschildt and coworkers have shown that the induction of pro-inflammatory cytokines by LPS treatment of macrophages could be prevented by inhibiting PARP (Hauschildt et al., 1997). An anti-inflammatory effect of PARP activity suppression either induced by Parp1 gene knockout or pharmacological inhibition was also reported (Szabó et al., 1997). Also, LPS treatment of rats led to weakened endothelial functions, which could be alleviated by administration of PARP inhibitor 3-aminobenzamide (3AB) (Szabó et al., 1996).

In the USA, demand for primary care physician (PCP) services is increasing with expected shortage of 12,500 PCPs by 2025. People across the nation will be experiencing difficulty receiving medical care in a timely manner due to limited PCP availability. Currently, average waiting time for a PCP appointment is 19 days which will increase gradually. In addition, there is an increasing eligible patient pool due to Affordable Care Act resulting in 50-60 million office visits for low-acuity medical conditions. Other pain points for physicians include complex electronic health records, significant paperwork, overhead costs and decreasing reimbursements. Patients' pain points include longer wait times, significant costs associated office/ER visits,

The interactions occurring between the artery wall and the stent surfaces need to be studied considering the hyperelastic nature of the arteries. Injuries are caused on the artery surfaces due to stent implantation. It can be easily manifested that any external foreign structure implanted in the body can cause harm to the body. Especially the ends of the complicated stent designs may prick the artery walls. Or the interactive stresses acting on the vessel walls may concuss the walls if are beyond the materials bearable properties. It is hence necessary to first study the