Noradrenergic responses of peripheral organs to cyclophosphamide in mice

Karp, Jonathan; Szczytkowski, Jennifer L.; Gentile, Christopher F.

doi:10.1016/j.lfs.2004.04.020

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Of course, we cannot rule out other mechanisms that aside from the central nervous system play a role in the exacerbation of the sympathetic nerve activity during administration of DX and CY. Some investigators have reported that CY increases the concentration of norepinephrine in muscle tissue in an animal model (24). The increase in sympathetic outflow in our study does not seem associated with increased circulatory inflammatory responses since no significant changes in IL-6 levels plasma levels and hsCRP serum levels were found.…”

Section: Discussioncontrasting

confidence: 52%

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

Sales

Negrão

Testa

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Purpose 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 patients with breast cancer. Methods Sixteen 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. Results 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 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). Conclusions Adjuvant 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 Information São Paulo Research Foundation ‐ FAPESP This 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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Section: Discussioncontrasting

confidence: 52%

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

Sales

Negrão

Testa

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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“…cyclophospha-mide) and chemicals (e.g. pyrethroids, cocaine) that augment thymic CA release adversely affect efficiency of thymopoiesis, and thereby compromise the immune system efficiency in combating pathogens [69][70][71][72][73] .…”

Section: Introductionmentioning

confidence: 99%

Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity

Leposavić

Pilipović

Perišić

2011

Neuroimmunomodulation

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Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naïve T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via β₂- and α₁-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of β₂- and α₁-AR-expressing thymic nonlymphoid cells and the α₁-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving α₁-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naïve T cell output.

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“…In our analysis, cyclophosphamide exposure in combination with higher doses of vincristine or corticosteroids was associated with an increased risk for developing CAD, with relative risk ranging from 1.09 to 2.24. Although some documentation exists linking cyclophosphamide exposure to changes in HRV in mice 37 and in patients with hematological malignancies following high‐dose conditioning for hematopoietic stem cell transplantation, 38 we speculate that our association is driven by exposure to higher doses of vincristine or corticosteroids. Vincristine is a known neurotoxin, previously shown to be associated with HRV in children during induction chemotherapy 39 .…”

Section: Discussionmentioning

confidence: 74%

Cardiac autonomic dysfunction in survivors of childhood acute lymphoblastic leukemia: The St. Jude Lifetime Cohort Study

Christoffersen

Gibson

Pui

et al. 2020

Pediatric Blood & Cancer

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Background: Cardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment-related risk factors for CAD.Procedure: Participants were treated for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital between 1980 and 2003 (N = 338). A comparison group matched for race/ethnicity, age, and sex was also recruited (N = 325). Resting heart rate (HR) was assessed via electrocardiogram, and heart rate recovery (HRR) and exercise capacity were evaluated with submaximal cardiopulmonary exercise testing.Results: CAD was present in 33.7% of survivors and 27.6% of controls (P = 0.09). Although mean resting HR did not differ between survivors and controls (74 ± 12 vs 72 ± 12 beats per minute (bpm), P = 0.07), survivors had lower mean HRR than controls (22 ± 9 vs 25 ± 10 bpm; P < 0.001). Survivors with CAD had lower peak exercise tolerance (25.7 ± 6.5 vs 21.2 ± 4.9 mL/kg/min, P < 0.001) than those without. Survivors treated with cyclophosphamide in combination with vincristine ≥38 mg/m 2 and/or glucocorticoids ≥10 000 mg/m 2 were 1.56 (95% CI 1.09-2.24) times more likely to have CAD than those without this treatment. Obese survivors were 1.78 (95% CI:1.31-2.40) times more likely to have CAD than nonobese survivors (P < 0.001).Conclusion: CAD was present in over one third of survivors and was associated with lower exercise capacity. Obese survivors and those exposed to cyclophosphamide with high doses of vincristine and/or corticosteroids were at greatest risk. K E Y W O R D Sacute lymphoblastic leukemia, autonomic dysfunction, cardiac, chemotherapy, obesity, survivor Abbreviations: %, percent; ±, plus-minus sign; ≤, less than or equal to; ≥, more than or equal

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Noradrenergic responses of peripheral organs to cyclophosphamide in mice

Cited by 7 publications

References 28 publications

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

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

Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity

Cardiac autonomic dysfunction in survivors of childhood acute lymphoblastic leukemia: The St. Jude Lifetime Cohort Study

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