Assessment of hindlimb myopathy and mitochondrial bioenergetics in a unique mouse model of access‐related hand dysfunction

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Kim, Kyoungrae, Anderson, Erik M., Fazzone, Brian, Harland, Kenneth C., Hu, Qiongyao, Khattri, Ram B., Salyers, Zach, Palzkill, Victoria R., Cort, Tomas A., O'Malley, Kerri A., Berceli, Scott A., Scali, Salvatore T., Ryan, Terence E.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R2958

Introduction Access‐related hand dysfunction (ARHD) such as steal syndrome, neuromotor discoordination, and weakness is prevalent following arteriovenous fistula (AVF) placement in patients with end‐stage renal disease. Despite the progressive increase in symptomatic hemodialysis patients, currently no preclinical animal model exists to examine underlying mechanisms or develop novel therapeutics. Herein, we characterize the hindlimb pathology in a novel mouse model of iliac AVF. Methods Male 8‐week‐old C57BL/6J mice were randomly assigned to casein‐based chow (CON: n=6) or adenine diet (CKD: n=16) for 3 weeks and glomerular filtration rate (GFR) using FIT‐C inulin clearance was measured. On the day of operation, animals were allocated to receive either left common iliac AVF (CKD_AVF: n=10) or Sham (CON_Sham: n=6, CKD_Sham: n=6) surgery and remained on their original diet throughout the study. Hemodynamic changes, hindlimb grip strength, and gait pattern were assessed prior to and post‐operatively. After two weeks of surgery, the animals were euthanized to assess gastrocnemius mitochondrial respiratory capacity and morphological alterations in tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) muscles. Results Animals exposed to adenine diet had impaired kidney function (GFR in CON:441.3±54.2 µL/min vs. CKD: 165.1±118.3 µL/min, p