Low flow enhances platelet activation after acute experimental arterial injury

AbstractPurpose: Vascular smooth muscle cell (VSMC) proliferation and migration to the subintima or intimal hyperplasia (IH) occur after arterial injury and are thought to be induced by mitogenic factors released from activated platelets. Because low flow (LF) and shear have been attributed to the localization and progression of IH, we postulated that hemodynamic factors may regulate the degree of platelet activation, as measured by plasma thromboxane B2 (TXB2) and platelet-derived growth factor-AB (PDGF-AB) release at regions of experimental arterial injury. Methods: The right common carotid artery (CCA) was subjected to balloon injury in 18 New Zealand White male rabbits. Flow in the injured CCA was reduced by out-flow ligation (LF group, n = 6) or increased by ligation of the left CCA (high flow [HF] group, n = 6). In six other animals, flow was preserved (normal flow [NF] group). Mean blood flow and pressure in the right CCA were measured thereafter at 10 and 30 minutes. Plasma TXB2 and PDGF-AB levels were determined with the enzyme-linked immunosorbent assay method in each animal with blood samples taken systematically before injury (baseline) and in the distal CCA at similar time points. Results: At 10 minutes, mean blood flow was reduced from 20 ± 2 ml/min in the NF group to 7 ± 1 ml/min in the LF group animals (p < 0.01) and increased to 32 ± 2 ml/min in the HF group animals (p < 0.05). Mean arterial blood pressure did not differ among the groups. Hemodynamic parameters were similar at 10 and 30 minutes. TXB2 levels were more than fourfold greater in the LF group than in the HF and NF groups at both time points (p < 0.05). In addition, there was a twofold increase in plasma PDGF-AB level at 10 minutes in the LF group compared with baseline levels (p < 0.05). Conclusion: Platelet activation at regions of acute vascular injury was determined to be flow dependent. Upregulated platelet activity in low flow conditions may be due to increased platelet exposure time to subendothelial collagen and is greatly attenuated if normal or increased flow is present.(J Vasc Surg 1998;27:910-8.

Response of Arteries to Near-Wall Fluid Dynamic Behavior,&quot;

Arteries are living tissues which react and adapt to their environment, particularly in relation to changes in the rate of blood flow required to supply peripheral tissues or organs. Medium and small size arteries increase in diameter in response to short-term demands for increased flow and decrease in diameter in the event of diminished demands. Such immediate reactions are regulated primarily by vasoactive substances acting directly on smooth muscle cells of the media or by release of smooth muscle relaxation or contraction factors elaborated by endothelial cells. Chronic or long-term changes in arterial diameter appear to be governed directly by near-wall flow phenomena, e.g. the fluid dynamic wall shear. Recent evidence suggests that the normal tendency of arteries to respond to long-term changes in the shear field can result in intimal thickening and that this response may also favor the development of atherosclerosis. Thus, there appears to be a close relationship between fluid dynamics and the structure of arteries. From the fluid dynamics viewpoint, the pulsatile, three dimensional nature of blood flow requires sophisticated experimental methods in order to provide adequate data for correlation with biological studies. Research within the past decade has led to the conclusion that arteries seek a vessel diameter-blood flow combination which results in a flow-induced mean wall shear stress of approximately 15 dynes/sq.cm. If this value is chronically exceeded, vessel enlargement develops. If normal baseline shear stress is not restored by this increase in radius, the local response may continue. Conversely, reduced wall shear tends to induce intimal thickening in order to reduce lumen radius and thus increase wall shear toward normal levels. Under certain conditions this reaction may progress to the development of atherosclerotic plaques. Despite this knowledge, key points remain to be clarified. Is it the wall shear stress or the wall shear rate which determines the reaction? The former possibility implies that a mechanical shear-related stimulus is at the heart of the biological response mechanisms while the latter suggests a mass transportrelated mechanism

Human Coronary Artery Remodeling, Beginning and End of the Atherosclerotic Process

BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied. MATERIALS AND METHODS: The study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group –vessel) means, and related to stage of pathology. RESULTS: Pre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima. CONCLUSIONS: The findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process

Influences of Geometric Configurations of Bypass Grafts on Hemodynamics in End-to-Side Anastomosis

BACKGROUND: Although considerable efforts have been made to improve the graft patency in coronary artery bypass surgery, the role of biomechanical factors remains underrecognized. The aim of this study is to investigate the influences of geometric configurations of the bypass graft on hemodynamic characteristics in relation to anastomosis. MATERIALS AND METHODS: The Numerical analysis focuses on understanding the flow patterns for different values of inlet and distal diameters and graft angles. The Blood flow field is treated as a two-dimensional incompressible laminar flow. A finite volume method is adopted for discretization of the governing equations. The Carreau model is employed as a constitutive equation for blood. In an attempt to obtain the optimal aorto-coronary bypass conditions, the blood flow characteristics are analyzed using in vitro models of the end-to-side anastomotic angles of 45degrees, 60degrees and 90degrees. To find the optimal graft configurations, the mass flow rates at the outlets of the four models are compared quantitatively. RESULTS: This study finds that Model 3, whose bypass diameter is the same as the inlet diameter of the stenosed coronary artery, delivers the largest amount of blood and the least pressure drop along the arteries. CONCLUSION: Biomechanical factors are speculated to contribute to the graft patency in coronary artery bypass grafting.ope

Shear-Mediated Dilation of the Internal Carotid Artery Occurs Independent of Hypercapnia.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial carbon dioxide was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined the hypothesis that, following a 30-second transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants the partial pressures of end-tidal O2 and CO2, ventilation (pneumotachography), blood pressure (finger-photoplethysmography), heart-rate (electrocardiogram), internal carotid artery flow, diameter and shear stress (high resolution duplex ultrasound) and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-minute steady state and transient 30-second hypercapnic tests (both +9mmHg CO2). Internal carotid artery dilation was lower in the transient, compared to the steady state hypercapnia (3.3±1.9% vs. 5.3±2.9%, respectively; P<0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both the transient (time: 16.8±13.2s vs. 59.4±60.3s; P<0.01) and steady state (time: 18.2±14.2s vs. 110.3±79.6s; P<0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient (r(2)=0.44; P<0.01), but not steady state (r(2)=0.02; P=0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans

Coronary Artery Perforation Following Implantation of a Drug-Eluting Stent Rescued by Deployment of a Covered Stent in Symptomatic Myocardial Bridging

We successfully rescued a patient whose coronary artery perforated following implantation of a drug-eluting stent (DES), by deploying a stent-graft in symptomatic myocardial bridging. Our case demonstrated that coronary perforation could be handled without difficulty when perforated myocardial bridging is confined to the interventricular groov

Low wall shear stress predicts subsequent development of wall hypertrophy in lower limb bypass grafts

Background: Venous grafts commonly develop myointimal hyperplasia, which can lead to stenoses and, ultimately, with expression of adhesion molecules, lumenal occlusion. The aim of the present study was to investigate whether wall shear stress measured post-operatively would predict subsequent myointimal hypertrophy in lower limb venous bypass grafts. Methods: Magnetic resonance imaging and ultrasound were performed in a cohort of patients following lower limb venous bypass graft surgery for peripheral arterial disease at baseline (1-2 weeks) and at follow-up (9-12 months). Wall shear stress was determined at baseline using computational fluid dynamics techniques and intima-media thickness along the length of the graft was measured by ultrasound at baseline and follow up. Results: Complete follow-up was possible in eight patients, in whom low wall shear stress at baseline predicted high intima-media thickness. The relationship between wall shear stress (WSS) and intima-media thickness (IMT) was curvilinear with IMT increasing sharply at lower levels of WSS (IMT >1.0 mm at <0.3 Pa). Conclusions: Low wall shear stress is associated with subsequent increase in myointimal thickness in lower limb venous bypass grafts. This is believed to be the first prospective study in humans to demonstrate the relationship between low wall shear stress and myointimal thickening and indicates a likely causative role for low wall shear stress in the development of myointimal hyperplasia. © 2009 Association for Research into Arterial Structure and Physiology.Published versio

Role of fibrinopeptide B in early atherosclerotic lesion formation

The development of atheroselerotic lesions involves many cell types, including macrophages. Fibrinopeptide B (FPB) has been shown to be a potent chemotactic agent for macrophages, which are abundant as intimal foam cells in atherosclerotic lesions, especially in cholesterol-fed rabbits. We hypothesize that intimal low-density lipoproteins also cause fibrinogen in the intima to release FPB and that FPB attracts macrophages in response to the high lipid levels associated with lesion development. To test our hypothesis, we used an atherosclerotic model. Silk sutures containing either FPB, fibrinopeptide A (FPA), lipopolysaccharide (LPS), or saline control were prepared. One suture of each type was placed in the adventitia of the femoral artery of a rabbit. Animals were killed at 1 or 2 weeks. Only vessels exposed to either FPB or LPS showed significant intimal thickening in the region adjacent to the suture site. Semi-thin electron microscopic sections indicated that the intimal wall was highly cellular and that many cells contained lipid vacuoles after 2 weeks. These sections also showed that the endothelium remained intact and that no injury to the media of the artery had occurred. Electron microscopy of the tissue samples showed the proliferation of smooth muscle cells and deposition of extracellular matrix in the 2-week animals, whereas foam cells were present in the l-week animals. We conclude that FPB does indeed attract macrophages to the intima and that these macrophages may become foam cells. The model we have developed can be used to study possible mechanisms for the entry of macrophages into the intima during early lesion development and to further understand the complex interactions of FPB, fibrinogen, and lipids in atherosclerotic lesion development. T he development ofatherosclerotic lesions is a complex process and probably involves interactions between circulating blood elements, including serum lipids and white blood cells (e.g., monocytes and lymphocytes), and the arterial wall, including endothelial cells and smooth muscle cells of the media. The nature of this interaction and the role of blood-borne cells in this process, especially macrophages, are not completely understood. From the Departments of Surgery and Fibrinogen is a serum protein with a major role in blood clotting. It may also be the source of a chemotactic factor for the monocytes that accumulate as intimal foam cells during atherogenesis. Three considerations point to such a mechanism. First, diet-induced hyperlipemia is associated with an increased influx of ape-B-containing lipoproteins into the intima The complex process involving the interactions of fibfinogen, FPB, and lipoproteins is not fully understood. One possible mechanism is that when fibrinogen binds to lipoproteins with the requisite phospholipid surface, the lipids become oxidized so that they cannot exit the vessel wall. Since there is also a release of FPB, we hypothesize that FPB attracts macrophages to deal with the offending agent (the altered lipids). Previous studies by Prescott et al MATERIAL AND METHODS Sixteen New Zealand White rabbits (3.0 to 3.5 kg) were used. 4.0 silk sutures were prepared by soaking them 15