Influences of renal insufficiency and ischemia on mitochondrial bioenergetics and limb dysfunction in a novel murine iliac arteriovenous fistula model

Anderson, Erik; Kim, Kyoungrae; Fazzone, Brian; Harland, Kenneth C.; Hu, Qiongyao; Salyers, Zach; Palzkill, Victoria R.; Cort, Tomas A.; Kunz, Eric M.; Martin, Andrew; Neal, Dan; O’Malley, Kerri; Berceli, Scott A.; Ryan, Terence E.; Scali, Salvatore T.

doi:10.1016/j.jvssci.2022.10.001

Cited by 2 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One week following arrival, all mice were switched to a 20% casein-based chow diet. After 1 week on casein diet, all mice were fed a 0.2% adenine-supplemented casein chow to induce chronic kidney disease prior to the AVF surgery and remained on the adenine diet throughout the study as previously described 18 , 23 , 24 , 32 – 35 . All animals were provided both food and water ad libitum for the duration of the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Three weeks after the 0.2% adenine diet application, animals underwent microsurgery to create an AVF on the left common iliac vessels as previously described 18 , 19 , 23 . Briefly, mice were anesthetized with initial isoflurane anesthesia, buprenorphine HCl (0.1 mg/kg) was administered subcutaneously, and the abdominal hair was removed using a pen-trimer.…”

Section: Methodsmentioning

confidence: 99%

“…The patency of AVF and hemodynamics of infrarenal aorta and inferior vena cava were assessed using a high-frequency duplex ultrasound system (30–50 MHz, Vevo 2100, VisualSonics, Inc. Toronto, Ontario, Canada) 4 days prior to the euthanasia as previously described 18 , 23 , 37 . After induction of general anesthesia via isoflurane, mice were placed on a prewarmed 3D positioning platform in a supine position and their extremities were fixed with tape.…”

Section: Methodsmentioning

confidence: 99%

“…Post-operative blood perfusion to the TA muscle and ventral paw was assessed using a laser Doppler flowmeter (moorVMS-LDF, Moor Instruments) immediately after the AVF creation and post-operatively on days 3 and 13 as described previously 23 . The average perfusion flux (~ 10 s) was determined, and perfusion recovery was calculated as a percentage of AVF limb (left) relative to the contralateral non-surgical limb (right).…”

Section: Methodsmentioning

confidence: 99%

“…To begin to explore whether skeletal muscle pathology contributes to ARHD following AVF creation, our group developed a novel mouse model in which an AVF can be created in the iliac vascular bundle allowing examination of limb pathophysiology 18 , 19 which is not possible using alternative pre-clinical models using aortic or carotid vessels 20 – 22 . In this murine iliac AVF model, mice have been shown to exhibit hindlimb weakness, gait abnormalities, and muscle mitochondrial abnormalities 18 , 23 , 24 . Oxidative stress and mitochondrial dysfunction have been frequently reported in the skeletal muscle of rodents and human patients with CKD 10 – 12 , 16 , 25 – 28 .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease

Kim,

Fazzone,

Cort

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Hand dysfunction is a common observation after arteriovenous fistula (AVF) creation for hemodialysis access and has a variable clinical phenotype; however, the underlying mechanism responsible is unclear. Grip strength changes are a common metric used to assess AVF-associated hand disability but has previously been found to poorly correlate with the hemodynamic perturbations post-AVF placement implicating other tissue-level factors as drivers of hand outcomes. In this study, we sought to test if expression of a mitochondrial targeted catalase (mCAT) in skeletal muscle could reduce AVF-related limb dysfunction in mice with chronic kidney disease (CKD). Male and female C57BL/6J mice were fed an adenine-supplemented diet to induce CKD prior to placement of an AVF in the iliac vascular bundle. Adeno-associated virus was used to drive expression of either a green fluorescent protein (control) or mCAT using the muscle-specific human skeletal actin (HSA) gene promoter prior to AVF creation. As expected, the muscle-specific AAV-HSA-mCAT treatment did not impact blood urea nitrogen levels (P = 0.72), body weight (P = 0.84), or central hemodynamics including infrarenal aorta and inferior vena cava diameters (P > 0.18) or velocities (P > 0.38). Hindlimb perfusion recovery and muscle capillary densities were also unaffected by AAV-HSA-mCAT treatment. In contrast to muscle mass and myofiber size which were not different between groups, both absolute and specific muscle contractile forces measured via a nerve-mediated in-situ preparation were significantly greater in AAV-HSA-mCAT treated mice (P = 0.0012 and P = 0.0002). Morphological analysis of the post-synaptic neuromuscular junction uncovered greater acetylcholine receptor cluster areas (P = 0.0094) and lower fragmentation (P = 0.0010) in AAV-HSA-mCAT treated mice. Muscle mitochondrial oxidative phosphorylation was not different between groups, but AAV-HSA-mCAT treated mice had lower succinate-fueled mitochondrial hydrogen peroxide emission compared to AAV-HSA-GFP mice (P < 0.001). In summary, muscle-specific scavenging of mitochondrial hydrogen peroxide significantly improves neuromotor function in mice with CKD following AVF creation.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease

Kim,

Fazzone,

Cort

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

N-acetylcysteine treatment attenuates hemodialysis access-related limb pathophysiology in mice with chronic kidney disease

Kim,

Cort,

Kunz

et al. 2023

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The objective of this study was to determine if treatment with N-acetylcysteine (NAC) could reduce access-related limb dysfunction in mice. Male and female C57BL6J mice were fed an adenine supplemented diet to induce chronic kidney disease prior to surgical creation of an arteriovenous fistula (AVF) in the iliac vascular bundle. AVF creation significantly increased peak aortic and infrarenal vena cava blood flow velocities, but NAC treatment had no significant impact indicating that fistula maturation was not impacted by NAC treatment. Hindlimb muscle and paw perfusion recovery and muscle capillary density in the AVF limb were unaffected by NAC treatment. However, NAC treatment significantly increased the mass of the tibialis anterior ( P=0.0120) and soleus ( P=0.0452) muscles post-AVF. There was a significant main effect of NAC treatment on hindlimb grip strength at post-operative day (POD) 12 ( P=0.0003), driven by significantly higher grip strength in both male ( P=0.0273) and female ( P=0.0031) mice treated with NAC. There was also a significant main effect of NAC treatment on walking speed at POD12 ( P=0.0447), and post-hoc testing revealed improvement in NAC male mice ( P=0.0091). The area of post-synaptic acetylcholine receptors ( P=0.0263) and motor endplates ( P=0.0240) were also increased by NAC treatment. Interestingly, hindlimb skeletal muscle mitochondrial oxidative phosphorylation was trending higher in NAC female mice but was not statistically significant ( P=0.0973). Muscle glutathione levels and redox status were not significantly impacted by NAC treatment in either sex. In summary, NAC treatment attenuated some aspects of neuromotor pathology in mice with chronic kidney disease following AVF creation.

show abstract

Influences of renal insufficiency and ischemia on mitochondrial bioenergetics and limb dysfunction in a novel murine iliac arteriovenous fistula model

Cited by 2 publications

References 47 publications

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease

N-acetylcysteine treatment attenuates hemodialysis access-related limb pathophysiology in mice with chronic kidney disease

Contact Info

Product

Resources

About