Numerical simulations of patient-specific models with multiple plaques in human peripheral artery: a fluid-structure interaction analysis

© 2020, The Author(s). Atherosclerotic plaque in the femoral is the leading cause of peripheral artery disease (PAD), the worse consequence of which may lead to ulceration and gangrene of the feet. Numerical studies on fluid-structure interactions (FSI) of atherosclerotic femoral arteries enable quantitative analysis of biomechanical features in arteries. This study aims to investigate the hemodynamic performance and its interaction with femoral arterial wall based on the patient-specific model with multiple plaques (calcified and lipid plaques). Three types of models, calcification-only, lipid-only and calcification-lipid models, are established. Hyperelastic material coefficients of the human femoral arteries obtained from experimental studies are employed for all simulations. Oscillation of WSS is observed in the healthy downstream region in the lipid-only model. The pressure around the plaques in the two-plaque model is lower than that in the corresponding one-plaque models due to the reduction of blood flow domain, which consequently diminishes the loading forces on both plaques. Therefore, we found that stress acting on the plaques in the two-plaque model is lower than that in the corresponding one-plaque models. This finding implies that the lipid plaque, accompanied by the calcified plaque around, might reduce its risk of rupture due to the reduced the stress acting on it

Clinical pharmacist implementation of a medication assessment tool for long-term management of atrial fibrillation in older persons

Background: Optimisation of drug therapy is important in the older population and may be facilitated by medication assessment tools (MATs). Objective: The purpose of the study was to evaluate whether appropriateness of drug therapy and clinical pharmacist intervention documentation improved following implementation of a previously developed MAT for the long-term management of atrial fibrillation (MAT-AF). Methods: Adherence to MAT-AF review criteria and clinical pharmacist intervention documentation was assessed by the researcher pre-MAT implementation in 150 patients aged ≥60 years admitted to a rehabilitation hospital with a diagnosis of atrial fibrillation. MAT-AF was introduced as a clinical tool in the hospital for identification of pharmaceutical care issues in atrial fibrillation patients. Adherence to MAT-AF and pharmacist intervention documentation were assessed by the researcher post-MAT implementation for a further 150 patients with the same inclusion criteria. Logistic regression analysis and measurement of odds ratio was used to identify differences in adherence to MAT-AF pre- and post-MAT implementation. The differences between two population proportions z-test was used to compare pharmacist intervention documentation pre- and post-MAT implementation. Results: Adherence to MAT-AF criteria increased from 70.9% pre-implementation to 89.6% post-implementation. MAT-AF implementation resulted in a significant improvement in prescription of anticoagulant therapy (OR 4.07, p<0.001) and monitoring of laboratory parameters for digoxin (OR 10.40, p<0.001). Clinical pharmacist intervention documentation improved significantly post-implementation of MAT-AF (z-score 20.249, p<0.001). Conclusions: Implementation of MAT-AF within an interdisciplinary health care team significantly improved the appropriateness of drug therapy and pharmacist intervention documentation in older patients with atrial fibrillation

In vitro study of the deployment performance of 3D printed stents in the diseased artery with the lipid arterial plaques

Atherosclerotic plaque is one of the arterial diseases which builds up in the arterial wall and can be identified by the composition of the plaque. Atherosclerosis causes the narrowing or occlusions of the arterial lumen leading to cardiovascular event. Percutaneous (keyhole) endovascular stenting has become the most common revascularisation method due to its minimum invasive nature and low complication rate. The stents, mostly fabricated by laser machines, have uniform geometries which are not ideal to treat the diseased arteries with lesion-specific properties. In addition, the effect of arterial plaque compositions on the performance of stents is not fully investigated. In this study, the deployment performance of the stents with the varied design, made of the 316L stainless steel and fabricated by additive manufacturing (AM) technology, were investigated. An in vitro experiment was conducted to test the influence of the atherosclerotic plaque compositions at 55% stenosis on the commercial and AM fabricated stents. Two artificial plaques (lipid and calcified) were prepared manually, and their mechanical testing were conducted using an unconfined compression test. Two types of stents, printed and commercial stents, were used to treat the diseased artificial artery, and the data of the pressure and diameter were collected simultaneously when the stent inflation pressure was applied. The results show that the mechanical property of the artificial lipid plaques was very similar to the real lipid plaque that observed from clinical study. From the deployment performance test for these two types of stents, it was observed that as the pressure inside of balloon increases, the diameters measured at the external wall of the artificial artery also increase when the pressure is above 4 atm. Overall, there is a close linear relationship between pressure and arterial wall movement with lipid plaque in both printed and commercial stents though that the stent made of AM technology is less flexible and has lower elastic property than the commercial one

In-vitro Study of Effect of the Design of the Stent on the Arterial Waveforms

Peripheral arterial disease (PAD) occurs as a result of atherosclerosis, which involves plaque formation on the inner walls of the arteries. This reduces the size of the vessel’s lumen and restricts blood flow to the leg muscles, leading to pain, the death of tissue and even the amputation of the lower leg. One treatment method for PAD is the placement of a stent, which acts as a scaffold holding open the artery, increasing blood flow to the lower extremities. However, the stents for PAD are known to fail more regularly due to the complicated biomechanical conditions such as heavy calcified and long atherosclerotic lesions. Stenting in the peripheral arteries still fail in 25% of vessels after 2 years. One of the major influences on the rate of restenosis is the rate at which the platelets become activated. This activation is controlled by changes of wall shear stress, which is in turn influenced by the flow rate, and pressure. This study hypothesizes that stents in the arteries can cause the reflection of the waveform, which would alter the flow rate and pressure waveforms, causing increase in the rate of restenosis. This is potentially why various in-vivo studies have found that stents with thicker struts cause increased levels of restenosis.In this study, the effect of stent design on haemodynamic flow will be investigated, with the intention of optimising the designs currently in use in medicine. By setting up an in-vitro experiment, with an artificial artery, it is possible to record the flow rate, change in diameter and pressure caused to the blood flow by the stent. In this experiment, it is intended to use a series of 3D printed stents of two designs (Palmaz and Zigzag), with differing, strut thickness to determine which causes the most reflection, in an attempt to optimise the stent design

Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

BACKGROUND: Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. METHODS: Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. RESULTS: Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. CONCLUSIONS: These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion

Patient-centred training for pharmaceutical good distribution practice in Pharmacy of Your Choice (POYC)

The World Health Organization (WHO) advocates for a "responsive" healthcare system that meets people's needs by maintaining patient-centeredness. This is achieved by keeping in perspective patient's values and preferences in the delivery of care. In Malta, the Ministry of Health's Pharmacy of Your Choice (POYC) is the distribution arm for chronic medications through private community pharmacies for free on the national health system. POYC unit strives to offering quality pharmaceutical service through ensuring entitlement and Good Distribution practices of medicinal products.peer-reviewe

Strategies for Inhibiting Advanced Glycation Endproduct (Age) Induced Vascular Calcification in a Smooth Muscle Cell Culture Model

Vascular calcification is implicated in a range of cardiovascular disease mechanisms, leading to an associated increase in morbidity and mortality. One such trigger are advanced glycation endproducts (AGEs), the tissue accumulation of which increases with age and is more prevalent in diabetic subjects due to oxidative stress and poor glycaemic control. The aim of this study was to investigate the osteogenic potential of AGEs and elucidate mechanisms of inhibiting these processes in a smooth muscle cell (SMC) culture model. Osteogenic differentiation of SMCs was induced using β-glycerophosphate (β-GP), carboxymethyllysine (CML), carboxyethyllysine (CEL) methylglyoxal (MGO) and glycated low density lipoprotein (gly-LDL). The cells were subsequently treated with aminoguanidine (AG), an inhibitor of AGE formation, and novel glycomimetic compounds in order to determine their anti-calcification potential in vitro using qPCR, ELISA, Alkaline phosphatase (ALP) activity and Alizarin red staining. Gly-LDL (10 µg/ml) and CML (2.5nM) increased the level of calcification observed compared to the β-GP (5 mM) positive control after 21 days (p < 0.05), with gly-LDL induced calcification apparent after 14 days. Both AG (250 µM) and the novel glycomimetic compounds reduced the level of mineralisation observed at 21 days compared with osteogenic treatments (p < 0.05). CEL (2.5 nM) and MGO (0.1 mM) both induced calcification, however mineralization was not as extensive as with β-GP. When compared to the structure of CML, the side-chain of CEL contains an extra methyl group, suggesting this group impacts RAGE receptor binding. It was also shown that β-GP combined with increased glucose concentration induced more extensive calcification unlike low glucose levels and β-GP alone. ALP activity, when stimulated with β-GP, CML and gly-LDL was greater at day 4 than at day 7, with AG reducing ALP activity measurements at day 4. Gly-LDL increases gene expression of OCN at day 4 compared with β-GP and CML, however this was reduced at day 7, corresponding with an increased expression of OPN and OPG. NOTCH-3 gene expression was also reduced at day 7. Gene expression of OPN, OPG and NOTCH-3 were reduced at both day 4 and day 7 compared with osteogenic treatments (β-GP, CML and gly-LDL). In summary, we conclude that gly-LDL and CML are potent inducers of calcification compared with β-GP, and that their osteogenic potential can be modulated by both AG and novel glycomimetic compounds

Carbon monoxide-Releasing Molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats

<p>Abstract</p> <p>Background</p> <p>Hepatic ischemia-reperfusion injury (I/Ri) is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO) by application of so-called CO-releasing molecules (CORMs). Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model.</p> <p>Methods</p> <p>Forty male Wistar rats were randomly assigned into four groups (n = 10). Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg), which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration.</p> <p>Results</p> <p>A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in nuclear extracts of liver homogenates. Moreover, CORM-2 treatment resulted in reduced serum levels of pro-inflammatory cytokines TNF-α and IL-6 and down-regulation of the adhesion molecule ICAM-1 in the endothelial cells of liver. In line with these findings, CORM-2 treatment reduced the accumulation of neutrophils in the liver upon I/Ri. Similar treatment with an inactive variant of CORM-2 (iCORM-2) did not have any beneficial effect on the extent of liver I/Ri.</p> <p>Conclusions</p> <p>CORM-2 treatment at the time of reperfusion had several distinct beneficial effects on severity of hepatic I/Ri that may be of therapeutic value for the prevention of tissue damage as a result of I/Ri during hepatic surgery.</p