Ultrastructural alterations and mitochondrial dysfunction in skeletal muscle of peripheral artery disease patients: implications for early therapeutic interventions.

Peripheral artery disease (PAD) is an atherosclerotic condition that impairs blood flow to the lower extremities, resulting in myopathy in affected skeletal muscles. Improving our understanding of PAD and developing novel treatment strategies necessitates a comprehensive examination of cellular structural alterations that occur in the muscles with disease progression. Here we aimed to employ electron microscopy to quantify skeletal muscle ultrastructural alterations responsible for the myopathy of PAD.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD.

Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients.

Diet-induced obesity augments ischemic myopathy and functional decline in a murine model of peripheral artery disease.

Peripheral artery disease (PAD) causes an ischemic myopathy contributing to patient disability and mortality. Most preclinical models to date use young, healthy rodents with limited translatability to human disease. Although PAD incidence increases with age, and obesity is a common comorbidity, the pathophysiologic association between these risk factors and PAD myopathy is unknown.

Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality.

Background: Peripheral arterial disease (PAD) causes leg muscle damage due to inadequate perfusion and increases cardiovascular events and mortality 2- to 3-fold. It is unclear if PAD is a biomarker for high-risk cardiovascular disease or if skeletal muscle injury harms arterial health. The objective of this work is to test if serum myoglobin levels (myoglobinemia) are a marker of PAD, and if so, whether myoglobin impairs vascular health.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

Objective: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure.

Methods: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium.

Current status of pulmonary artery denervation.

Pulmonary hypertension is a progressive disease with a poor long-term prognosis and high mortality. Pulmonary artery denervation (PADN) is emerging as a potential novel therapy for this condition. The basis of pursuing a sympathetic denervation strategy has its origins in a body of experimental translation work that has demonstrated that denervation can reduce sympathetic nerve activity in various animal models.

Chemical and cryo-collection of muscle samples for transmission electron microscopy using Methacarn and dimethyl sulfoxide.

Muscle samples are commonly chemically fixed or frozen immediately upon collection for biochemical and morphological analysis. Certain fixatives such as glutaraldehyde and osmium tetroxide are widely used for transmission electron microscopy (TEM) and lead to adequate preservation of muscle ultrastructure, but do not preserve the molecular features of samples. Methacarn is suggested to be a preferable chemical fixative for light microscopy because it maintains immunohistological features of samples.

MicroRNAs in peripheral artery disease: potential biomarkers and pathophysiological mechanisms.

Peripheral artery disease (PAD) is a disease of atherosclerosis in the lower extremities. PAD carries a massive burden worldwide, while diagnosis and treatment options are often lacking. One of the key points of research in recent years is the involvement of microRNAs (miRNAs), which are short 20-25 nucleotide single-stranded RNAs that can act as negative regulators of post-transcriptional gene expression.

Skeletal muscle MiR-210 expression is associated with mitochondrial function in peripheral artery disease patients.

Previous studies have demonstrated that circulating microRNA (miR)-210 levels are elevated in peripheral artery disease (PAD) patients. MiR-210 is known to be a negative regulator of mitochondrial respiration; however, the relationship between miR-210 and mitochondrial function has yet to be studied in PAD. We aimed to compare skeletal muscle miR-210 expression of PAD patients to non-PAD controls (CON) and to examine the relationship between miR-210 expression and mitochondrial function.

High-Fat Diet Augments the Effect of Alcohol on Skeletal Muscle Mitochondrial Dysfunction in Mice.

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks.

Management of Arterio-Venous Fistula Side Branches During Maturation: Ligation or Coil Embolization.

Objective: Failure of maturation of arteriovenous fistulae (AVF) remains an ongoing concern for dialysis access. One etiology is the presence of side branches that divert flow from the main AVF channel. This study aims to evaluate the outcomes of endovascular and open surgical interventions for AVF side branches in the setting of maturation failure.

Endothelial cell-derived pro-fibrotic factors increase TGF-β1 expression by smooth muscle cells in response to cycles of hypoxia-hyperoxia.

Background: The vascular pathology of peripheral artery disease (PAD) encompasses abnormal microvascular architecture and fibrosis in response to ischemia-reperfusion (I/R) cycles. We aimed to investigate the mechanisms by which pathological changes in the microvasculature direct fibrosis in the context of I/R.

Methods: Primary human aortic endothelial cells (ECs) were cultured under cycles of normoxia-hypoxia (NH) or normoxia-hypoxia-hyperoxia (NHH) to mimic I/R.

Phytochemicals as Therapeutic Interventions in Peripheral Artery Disease.

Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients.

The "two-cut monorail" technique, for the over-the-wire removal of the Impella CP device.

The Impella is a percutaneously placed intra-arterial flow pump positioned across the aortic valve for circulatory support. A limitation of the Impella is that it lacks a central wire channel, to maintain intra-arterial wire access when removing the device. Open surgical arterial cutdown is needed for the removal of the Impella CP placed emergently, without the use of preclose sutures.

Extent of heel ulceration influences the outcomes in patients with isolated infrapopliteal limb threatening critical ischemia.

Background: The aim of the present study was to assess the effects of the extent of heel ulceration on the outcomes of limb threatening critical ischemia due to isolated infrapopliteal disease.

Methods: A retrospective review identified 989 patients with isolated infrapopliteal disease and heel ulceration treated from 2001 to 2018. The heel was defined as the back of the foot, extending from the Achilles tendon to around the plantar surface and covering the apex of the calcaneum bone.

Renal salvage using stent graft placement after acute renal artery occlusion with prolonged ischemic time.

Purpose: To describe a patient with acute renal artery occlusion who underwent successful revascularization procedure after experiencing a protracted ischemic period, which resulted in successful retrieval of renal function.

Case Report: A 58-year-old male with a history of left renal artery stenosis and stent graft placement presented with symptoms of chest pain, shortness of breath, and flank pain. The patient was admitted to the Intensive Care Unit with the diagnosis of multiorgan failure and subsequent anuria that led to the initiation of hemodialysis.

The Nitric Oxide System in Peripheral Artery Disease: Connection with Oxidative Stress and Biopterins.

Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress.

Implications of early failure of isolated endovascular tibial interventions.

Background: Endovascular tibial interventions for chronic limb-threatening ischemia are frequent, but the implications of early failure (≤30 days) of an isolated tibial intervention are still unclear. The aim of this study was to examine the patient-centered outcomes after early failure of isolated tibial artery intervention.

Methods: A database of patients undergoing lower extremity endovascular interventions between 2007 and 2017 was retrospectively queried.

Short-term contemporary outcomes for staged versus primary lower limb amputation in diabetic foot disease.

Background: Major lower extremity amputations remain among the most common procedures performed by vascular surgeons in patients with diabetes and its associated peripheral vascular disease. After major amputation, this population commonly suffers from high readmission rates, increased wound complications, and conversion to more proximal major amputations. These events impact quality in terms of cost, resources, and subjective quality of life.

Novel open technique for repair of endograft migration.

Widespread adoption of endovascular aneurysm repair has led to increased incidence of late complications, such as endograft migration. Treatment options have to be tailored to the patient's health, quality of proximal aorta, and extent of migration. Complete or partial endograft removal is associated with significant morbidity and mortality.

Recurrent Admissions for Respiratory Distress Caused by Large Renal AVF.

Renal arteriovenous fistulas (AVFs) are an uncommon complication of nephrectomy. In this report, we present the case of a 66-year-old female presenting with progressive dyspnea on exertion and exercise intolerance. She was diagnosed and treated for adult onset reactive airway disease.

Patient demographics and cardiovascular risk factors differentially influence geometric remodeling of the aorta compared with the peripheral arteries.

Background: Detailed knowledge of the dimensions and shape of the main arteries of the body and how they change with age and disease is important for understanding arterial pathophysiology and improving minimally invasive devices to treat arterial diseases. Our goal was to describe and compare geometric remodeling of the aorta and peripheral arteries in the context of patient demographics and cardiovascular risk factors.

Methods: Three-dimensional reconstructions of computed tomography angiography scans were performed in 122 subjects 5-93 years of age (mean 47 ± 24 years, 64 M/58 F).