Skeletal Muscle Oxygen Pressures in a Rodent Orthotopic Breast Cancer Model

Introduction: Breast cancer is the leading cause of cancer-related deaths in women worldwide. Further, many patients exhibit reduced maximal O 2 uptake and exercise intolerance that is inextricably linked to impaired skeletal muscle function. Skeletal muscle dysfunction is commonly attributed to the chemotoxic effects of adjuvant care, rather than risk factors, comorbidities, or tumor-derived signals (e.g., proinflammatory cytokines). While breast cancer, as an isolated condition, reduces exercise tolerance and impairs mitochondrial function in preclinical models, whether it effects skeletal muscle interstitial oxygen pressure (PO 2 is; O 2 delivery-to-mitochondrial demand matching) dynamics has not been studied. This investigation tested the hypothesis that breast cancer, as an isolated disease, would significantly alter the skeletal muscle PO 2 is kinetic response to contractions (reflected by a decreased time delay and accelerated tau). Methods: Female, retired breeder rats (Fischer 344) were randomized into control (n = 5) and breast cancer (n = 5) groups. Thereafter, saline (control) or mammary adenocarcinoma cells (13762 MATB III; 6 x 10 3 cells; breast cancer) was injected in the right abdominal mammary duct. Two weeks following injections, phosphorescence quenching determined the PO 2 is in the mixed-fiber type spinotrapezius muscle at rest and during the transition to electrically induced twitch contractions. Results: There were no differences in mean arterial pressure during rest or contractions between groups (P > 0.05). The tumor volume was 653 ± 246 mm 3 . Resting PO 2 is (30.6 ± 2.8 vs 31.8 ± 2.6, mmHg), time delay (8 ± 3 vs. 7 ± 2, s), amplitude (14.5 ± 1.9 vs. 16.7 ± 2.8, mmHg), tau (29 ± 8 vs. 25 ± 5, s), and end PO 2 is (18.1 ± 2.1 vs. 17.7 ± 1.6, mmHg) were not different between control and breast cancer rats, respectively (P > 0.05). Kinetic analyses revealed no differences between groups (P > 0.05). Conclusions: Contrary to our hypothesis, breast cancer rats did not display a pathological PO 2 is profile in the spinotrapezius muscle during contractions in comparison to control rats. This study provides suggests that chemotherapy and/or comorbidities play a more significant role in the defective O 2 transport found in breast cancer patients than the proinflammatory tumor itself, at least in the tumor development timeline measured herein. Investigating the physiological mechanisms underpinning exercise intolerance in breast cancer is critical to direct targeted interventions and whether these findings persist across varying fiber-types remains to be elucidated. SMILE Grant awarded to DCP from KSU CVM and the Graduate Cancer Research Scholarship awarded to REW from the Johnson Cancer Research Center at KSU. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.