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Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

ABSTRACT: OBJECTIVE:This study was undertaken to characterize structural and pharmacological properties of the pig popliteal artery in order to develop a novel system for the examination of lower limb blood flow regulation in a variety of cardiovascular pathologies, such as diabetes-induced peripheral artery disease. METHODS:Popliteal arteries were isolated from streptozocin-induced diabetic pigs or age-matched saline-injected control pigs for morphological study using transmission electron microscopy and for examination of vasoreactivity to pharmacological agents using wire myography. RESULTS:Transmission electron microscopy of the porcine popliteal artery wall revealed the presence of endothelial cell-smooth muscle cell interactions (myoendothelial junctions) and smooth muscle cell-smooth muscle cell interactions, for which we have coined the term "myo-myo junctions." These myo-myo junctions were shown to feature plaques indicative of connexin expression. Further, the pig popliteal artery was highly responsive to a variety of vasoconstrictors including norepinephrine, phenylephrine, and U46619, and vasodilators including acetylcholine, adenosine 5'-[?-thio] diphosphate, and bradykinin. Finally, 2 weeks after streptozocin-induced diabetes, the normalized vasoconstriction of the pig popliteal artery to norepinephrine was unaltered compared to control. CONCLUSIONS:The pig popliteal artery displays structural and pharmacological properties that might prove useful in future studies of diabetes-associated peripheral artery disease and other lower limb cardiovascular diseases.

SUBMITTER: Frederick NE

PROVIDER: S-EPMC6599728 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

Frederick Norman E NE Mitchell Ray R Hein Travis W TW Bagher Pooneh P

Microcirculation (New York, N.Y. : 1994) 20190507 6

<h4>Objective</h4>This study was undertaken to characterize structural and pharmacological properties of the pig popliteal artery in order to develop a novel system for the examination of lower limb blood flow regulation in a variety of cardiovascular pathologies, such as diabetes-induced peripheral artery disease.<h4>Methods</h4>Popliteal arteries were isolated from streptozocin-induced diabetic pigs or age-matched saline-injected control pigs for morphological study using transmission electron ...[more]

PMID: 30597676

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Project description:Background: Sports athletes, namely high-intensity practitioners, suffer from vascular remodeling overtime. The purpose of this study was to analyze the systolic and diastolic velocities' variation between non-athletes and futsal athletes by means of arterial lower limb doppler ultrasound. Additionally, we intended to verify if the velocity variations occur primarily at the systolic or the diastolic level and in which arteries. Methods: Seventy-six young males (mean ± SD: 24.9 ± 2.8 years old) volunteered to participate in this cross-sectional study and were divided into two groups: a futsal athletes group (n = 38; 24 ± 2.78 years) in the central region of Portugal playing on the 2nd national league with the same level of practice (16 ± 2.4 years of practice) and a non-athletes group (n = 38: 26 ± 1.8 years) who did not practice sports regularly and were not federated in any sport. All the subjects agreed to participate in the study with the aim of assessing the arterial lower limb through doppler ultrasound (Philips HD7 echograph with linear transducer 7-12 MHz). Results: Differences between groups (p ? 0.05) in the systolic velocity of the left deep femoral artery (p = 0.022; d = 0.546, small) and in the right superficial femoral artery (p = 0.028; d = -0.515, small) were found. We also found differences in the diastolic velocity: in the left common femoral artery (p = 0.002; d = -0.748, moderate), in the right deep femoral artery (p = 0.028; d = -0.521, small), in the right superficial femoral artery (p = 0.026; d = -0.522, small), in the right popliteal artery (p = 0.002; d = -0.763, moderate), and in the left popliteal artery (p = 0.007; d = -0.655, moderate). Moreover, the athletes' group presented the highest mean values, with the exception of the systolic velocity of the left deep femoral artery. In intragroup analysis of variance referring to systolic and diastolic velocities in arterial levels in the right and left arteries, differences were found in all analyses (p ? 0.05). Conclusions: We conclude that futsal athletes of our sample go through a process of changes such as increased blood flow velocity in systolic and diastolic cardiac phase in all studied lower limb arteries, showing that the remodeling occurs regardless of vessel radius. Our results reinforce the existence of vascular remodeling that may vary with the sport and its intensity.

Project description:IntroductionChronic limb-threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD) and is associated with high amputation rates, mortality and disease-related health care costs. In infrapopliteal arterial disease (IPAD), endovascular revascularization should be considered for the majority of anatomical and clinical subgroups of CLTI. However, a gap of high-quality evidence exists in this field. The aim of the Dutch Chronic Lower Limb-Threatening Ischemia Registry (THRILLER) is to collect real world data on popliteal and infrapopliteal endovascular interventions.MethodsTHRILLER is a clinician-driven, prospective, multicenter, observational registry including all consecutive patients that undergo a popliteal or infrapopliteal endovascular intervention in seven Dutch hospitals. We estimate that THRILLER will include 400-500 interventions annually. Standardized follow-up visits with wound monitoring, toe pressure measurement and duplex ultrasonography will be scheduled at 6-8 weeks and 12 months after the intervention. The independent primary endpoints are primary patency, limb salvage and amputation free survival. Patients must give informed consent before participation and will be included according to predefined reporting standards. A data log of patients who meet the inclusion criteria but are not included in the registry will be maintained. We intend to conduct the first interim analysis two years after the start of inclusion. The results will be published in a scientific journal.DiscussionDespite innovations in medical therapy and revascularization techniques, patients with CLTI undergoing endovascular revascularization still have a moderate prognosis. Previous prospective cohort studies were hampered by small sample sizes or heterogeneous reporting. Randomized controlled trials (RCTs) have high costs, potential conflicts of interest and give a limited reflection of daily practice. THRILLER aims to provide the largest prospective well phenotyped up-to-date dataset on treatment outcomes in CLTI patients to answer multiple underexplored research questions regarding diagnostics, medication, patient selection, treatment strategies and post intervention follow-up.

Project description:ObjectiveLower limb peripheral arterial disease in the symptomatic stage has a significant effect on patients´ functional disability. Before an intervention, an imaging diagnostic examination is necessary to determine the extent of the disability. This study evaluates cost-effectiveness of duplex ultrasonography (DUS), digital subtraction angiography (DSA), computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in the diagnostics of symptomatic patients with lower limb peripheral arterial disease indicated for endovascular or surgical intervention.MethodsDiscrete event simulation was used to capture lifetime costs and effects. Costs were calculated from the perspective of the health care payer, and the effects were calculated as quality-adjusted life year's (QALY's). The cost-effectiveness analysis was performed to pairwise compare CTA, MRA and DSA with DUS as the baseline diagnostic modality. A scenario analysis and probabilistic sensitivity analysis were carried out to evaluate the robustness of the results.ResultsIn the basic case, the DUS diagnostic was the least expensive modality, at a cost of EUR 10,778, compared with EUR 10,804 for CTA, EUR 11,184 for MRA, and EUR 11,460 for DSA. The effects of DUS were estimated at 5.542 QALYs compared with 5.554 QALYs for both CTA and MRA, and 5.562 QALYs for DSA. The final incremental cost-effectiveness ratio (ICER) value of all evaluated modalities was below the cost-effectiveness threshold whereas CTA has the lowest ICER of EUR 2,167 per QALY. However, the results were associated with a large degree of uncertainty, because iterations were spread across all cost-effectiveness quadrants in the probabilistic sensitivity analysis.ConclusionFor imaging diagnosis of symptomatic patients with lower limb peripheral arterial disease, CTA examination appears to be the most cost-effective strategy with the best ICER value. Baseline diagnostics of the DUS modality has the lowest costs, but also the lowest effects. DSA achieves the highest QALYs, but it is associated with the highest costs.

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Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

Publications

Morphological and pharmacological characterization of the porcine popliteal artery: A novel model for study of lower limb arterial disease.

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