2026-10-12T12:07:10Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32518032 2026-09-22T12:10:38Z category_27241 item_type_3 month_year_09_2026

<b>Cardiac Adaptation in a Murine Iliac Arteriovenous Fistula Model and the Impact of Sex and N-Acetylcysteine Supplementation</b> Kyoungrae Kim (10312460) Erik M. Andersen (24071540) Other health sciences not elsewhere classified AVF Cardiac adaptation N-acetylcysteine; oxidative stress <p dir="ltr">Hemodialysis arteriovenous fistulas(AVFs) promote left ventricular(LV) hypertrophy, a known predictor of cardiovascular mortality in patients with chronic kidney disease(CKD). AVF flow dynamics do not reliably predict cardiac remodeling suggesting additional causal biological determinants. Sex influences AVF maturation but its role in myocardial adaptation is unknown. We previously demonstrated sex-dependent protective effects of N-acetylcysteine(NAC) on skeletal muscle in a murine iliac AVF model. This study sought to evaluate whether iliac AVF creation produces compensated cardiac hypertrophy, investigate sex as a modifier of cardiac myocyte mitochondrial adaptation, and test NAC supplementation as a therapeutic strategy. Male and female C57BL/6J mice with adenine-induced CKD underwent iliac AVF or sham surgery with saline or NAC treatment. Ultrasound, echocardiography, and cardiac myocyte mitochondrial respiratory testing were performed. AVF creation produced significant aortic flow increases and corresponding diameter growth(male +64%, female +109%, p=0.001). Heart weight increased ~30-40mg over sham for both sexes(p=0.001). Female AVF mice demonstrated higher ejection fraction(94.8±5.1% vs. male-83.1±7.5%, p=0.001) and attenuated diastolic volume increase(32.8±11.8μl vs. 46.5±15.1μl, p=0.003). AVF inflow did not correlate with LV mass or ejection fraction. Cardiac mitochondrial oxidative phosphorylation(OXPHOS) was higher in female AVF mice(sex-effect p=0.01) and trended toward correlation with ejection fraction(p=0.06). NAC did not alter cardiac structure or function but was associated with a trend toward improved OXPHOS in females(p=0.09). Murine iliac AVF creation results in compensated cardiac hypertrophy without heart failure replicating observations documented in patients. Female sex is associated with greater cardiac myocyte mitochondrial function and adaptive remodeling, implicating sex-specific redox biology in AVF-related cardiac outcomes.</p> 2026-09-22T12:10:38Z Dataset Dataset 10.6084/m9.figshare.32518032.v3 https://figshare.com/articles/dataset/_b_Cardiac_Adaptation_in_a_Murine_Iliac_Arteriovenous_Fistula_Model_and_the_Impact_of_Sex_and_N-Acetylcysteine_Supplementation_b_/32518032 CC BY 4.0