Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer

Author(s):Show less -

Kluser Sales, Allan Robson ^[1] ; Negrao, Marcelo Vailati ^{[2, 3]} ; Testa, Laura ^[2] ; Ferreira-Santos, Larissa ^[1] ; Ramalho Groehs, Raphaela Villar ^[1] ; Carvalho, Bruna ^[1] ; Toschi-Dias, Edgar ^[1] ; Rocha, Natalia Galito ^[4] ; Martins Laurindo, Francisco Rafael ^[1] ; Debbas, Victor ^[1] ; Rondon, Maria Urbana P. B. ^[5] ; Mano, Max Sena ^[2] ; Hajjar, Ludhmila Abrahao ^{[1, 2]} ; Gehm Hoff, Paulo Marcelo ^[2] ; Kalil Filho, Roberto ^[1] ; Negrao, Carlos Eduardo ^[1]

Affiliation

^[1] Univ Sao Paulo, Heart Inst InCor, Med Sch, Av Dr Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, BR-05403904 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Med Sch, Canc Inst State Sao Paulo, Sao Paulo - Brazil

^[3] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 - USA

^[4] Fluminense Fed Univ, Dept Physiol & Pharmacol, Niteroi, RJ - Brazil

^[5] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 317, n. 1, p. H1-H12, JUL 2019.
• Web of Science Citations: 2

Abstract

The 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 women with breast cancer. Sixteen women (age: 47.0 +/- 2.0 yr; body mass index: 24.2 +/- 1.5 kg/m) 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/m (2)) and CY (600 mg/m(2)) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (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 at rest before, during, and after each session. Venous 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. MSNA 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 with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (P = 0.03, CHT vs. SL session). No difference in HR response was observed (P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW \& NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure. (AU)

• FAPESP's process: 14/11671-6 - Effect of high intensity interval training versus continuous moderate in the peripheral reflex mechanisms of control of the sympathetic activity in patients with heart failure
• Grantee: Allan Robson Kluser Sales
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants