Purpose: Physical activity (PA) guidelines suggest a link between PA, sedentary time, and sleep quality (SQ). Step cadence is an emerging proxy for PA intensity, with zero cadence (ZC) indicating sedentary time. No research has explored the relationship between ZC and SQ.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
April 2024
Background: Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
February 2024
The effect of exertional heat stroke (EHS) exposure on skeletal muscles is incompletely understood. Muscle weakness is an early symptom of EHS but is not considered a major target of multiorgan injury. Previously, in a preclinical mouse model of EHS, we observed the vulnerability of limb muscles to a second EHS exposure, suggesting hidden processes contributing to declines in muscle resilience.
View Article and Find Full Text PDFBackground: Lower extremity peripheral artery disease (PAD) is a growing epidemic with limited effective treatment options. Here, we provide a single-nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle.
Methods: We obtained gastrocnemius muscle specimens from 20 patients with PAD and 12 non-PAD controls.
Lower-extremity peripheral arterial disease (PAD) has increased in prevalence, yet therapeutic development has remained stagnant. Skeletal muscle health and function has been strongly linked to quality of life and medical outcomes in patients with PAD. Using a rodent model of PAD, this study demonstrates that treatment of the ischemic limb with insulin-like growth factor (IGF)-1 significantly increases muscle size and strength without improving limb hemodynamics.
View Article and Find Full Text PDFBackground: Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic solutes, which are ligands for AHR (aryl hydrocarbon receptor), are associated with limb amputation in PAD.
View Article and Find Full Text PDFChronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the cellular and physiological mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic toxins, many of which are ligands for the aryl hydrocarbon receptor (AHR), are associated with adverse limb outcomes in PAD.
View Article and Find Full Text PDFL-Kynurenine (L-Kyn), a product of tryptophan (Trp) catabolism, has been linked with impairments in walking speed, muscle strength/size, and physical function. The purpose of this pilot study was to develop a dietary model that elevates plasma L-Kyn levels in mice and characterize its impact on muscle health and function. Four-month-old C57BL6J male mice were randomized to either a L-Kyn supplemented (150 mg/kg) or chow diet for 10 weeks.
View Article and Find Full Text PDFAn estimated 700 million people globally suffer from chronic kidney disease (CKD). In addition to increasing cardiovascular disease risk, CKD is a catabolic disease that results in a loss of muscle mass and function, which are strongly associated with mortality and a reduced quality of life. Despite the importance of muscle health and function, there are no treatments available to prevent or attenuate the myopathy associated with CKD.
View Article and Find Full Text PDFCardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of oxidative stress, but the impact of reversible thiol oxidation on myocardial mitochondrial function in patients with HFrEF has not been investigated. In the present study, we assessed mitochondrial function in ventricular biopsies from patients with end-stage HFrEF in the presence and absence of the thiol-reducing agent dithiothreitol (DTT).
View Article and Find Full Text PDFObjective: The objective of the present study was to determine whether elevated levels of S100A8 and S100A9 (S100A8/A9) alarmins contribute to ischemic limb pathology.
Methods: Gastrocnemius muscle was collected from control patients without peripheral arterial disease (PAD; n = 14) and patients with chronic limb threatening limb ischemia (CLTI; n = 14). Mitochondrial function was assessed in permeabilized muscle fibers, and RNA and protein analyses were used to quantify the S100A8/A9 levels.
Tobacco smoke-related diseases such as chronic obstructive pulmonary disease (COPD) are associated with high healthcare burden and mortality rates. Many COPD patients were reported to have muscle atrophy and weakness, with several studies suggesting intrinsic muscle mitochondrial impairment as a possible driver of this phenotype. Whereas much information has been learned about muscle pathology once a patient has COPD, little is known about how active tobacco smoking might impact skeletal muscle physiology or mitochondrial health.
View Article and Find Full Text PDFBackground: Despite improved surgical approaches for chronic limb-threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. The purpose of this study was twofold: (1) to identify differences between the healthy adult and CLTI limb muscle proteome, and (2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation.
Methods And Results: Gastrocnemius muscle was collected from non-ischemic controls (n = 19) and either pre-interventional surgery (n = 10) or at amputation outcome (n = 29) CLTI patients.
Chronic kidney disease (CKD) results in reduced kidney function, uremia, and accumulation of uremic metabolites. Mitochondrial alterations have been suggested to play a role in the disease pathology within various tissues. The purpose of this study was to perform a comprehensive bioenergetic and proteomic phenotyping of mitochondria from skeletal muscle (SkM), cardiac muscle (CM), and renal tissue from mice with CKD.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2022
Background: Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke.
View Article and Find Full Text PDFPreclinical animal models of chronic kidney disease (CKD) are critical to investigate the underlying mechanisms of disease and to evaluate the efficacy of novel therapeutics aimed to treat CKD-associated pathologies. The objective of the present study was to compare the adenine diet and 5/6 nephrectomy (Nx) CKD models in mice. Male and female 10-wk-old C57BL/6J mice ( = 5-9 mice/sex/group) were randomly allocated to CKD groups (0.
View Article and Find Full Text PDFChronic limb threatening ischemia (CLTI) is the most severe manifestation of peripheral atherosclerosis. Patients with CLTI have poor muscle quality and function and are at high risk for limb amputation and death. The objective of this study was to interrogate the metabolome of limb muscle from CLTI patients.
View Article and Find Full Text PDFChronic kidney disease (CKD) results in the impaired filtration of metabolites, which may be toxic or harmful to organs/tissues. The objective of this study was to perform unbiased H nuclear magnetic resonance (NMR)-based metabolomics profiling of tissues from mice with CKD. Five-month-old male C57BL6J mice were placed on either a casein control diet or adenine-supplemented diet to induce CKD for 24 weeks.
View Article and Find Full Text PDFChronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute to skeletal myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are unknown. We employed a comprehensive mitochondrial phenotyping platform to elucidate the mechanisms of skeletal muscle mitochondrial impairment in mice with adenine-induced CKD.
View Article and Find Full Text PDFChronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6/J mice were subjected to a diet-induced model of CKD by delivery of adenine for six weeks.
View Article and Find Full Text PDFChronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics.
View Article and Find Full Text PDFBackground: Leadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers.
Methods: Patients receiving LCP (Micra [Medtronic, Minneapolis, MN, USA] and Nanostim [St.
Background: Pacing lead-related tricuspid regurgitation (TR), a recognized complication of ventricular pacing lead implantation, may be affected by lead position or diameter.
Objective: This study sought to determine the effect of ventricular pacing lead position and diameter on pacing lead-related TR.
Methods: A randomized prospective trial compared pacing leads in the right ventricular apex (RVA), right ventricular septum (RVS), or left ventricle via the coronary sinus (LV-CS) in a 1:1:1 fashion.
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