Abstract

PurposeThe purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in patients with breast cancer.MethodsSixteen women (age: 47.0±2.0 years; body mass index: 24.2±1.5 Kg.m−2) with stage II–III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600mg/m2) were administered in 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA, microneurography), calf blood flow (CBF, plethysmography) and calf vascular conductance (CVC), heart rate (HR, electrocardiography) and beat‐to‐beat blood pressure (BP) (Finger plethysmography) were measured before, during and after each session. Blood samples (5 mL) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs, flow cytometry), a surrogate marker for endothelial damage.ResultsMSNA and BP responses were increased (P<0.001), whereas CBF and CVC responses were decreased (P<0.001), during and after CHT session when compared to SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMPs response to CHT (P=0.03 vs. SL session). No difference in HR response was observed (p>0.05).ConclusionsAdjuvant CHT with DX and CY in patients treated for breast cancer leads to acute sympathetic hyperactivity and endothelial alterations, which results in reduced muscle vascular conductance and elevated systemic BP. These responses may anticipate susceptibility to CHT‐induced longterm cardiovascular alterations.Support or Funding InformationSão Paulo Research Foundation ‐ FAPESPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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