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

Sales, Allan Robson Kluser; Negrão, Marcelo V.; Testa, Laura; Ferreira‐Santos, Larissa; Groehs, Raphaela V; Carvalho, Bruna; Toschi‐Dias, Edgar; Rocha, Nazareth de Novaes; Laurindo, Francisco Rafael Martins; Debbas, Victor; Rondon, Maria Urbana Pinto Brandão; Mano, Max S.; Hajjar, Ludhmila Abrahão; Hoff, Paulo M.; Filho, Roberto Kalil; Negräo, Carlos Eduardo

doi:10.1152/ajpheart.00756.2018

Cited by 17 publications

(7 citation statements)

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“…In addition, several reports have shown the negative impact of Dox on vascular function in rodent models (11,16) or in the development of large vessel defects in subjects undergoing anticancer therapy (9,24). Fewer reports exist that have investigated the impact on the human microcirculation (27), none of which directly assessed MV function in the coronary circulation. This cumulative evidence suggests that systemic chemotherapy blunts the regulation of blood flow and impairs the vascular endothelium in functional microvessels.…”

Section: Discussionmentioning

confidence: 99%

Detrimental effects of chemotherapy on human coronary microvascular function

Hader

Zinkevich

Toro

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation. Microvascular (MV) dysfunction is an early indicator of numerous CV disease phenotypes, including heart failure. The goal of this study was to evaluate the direct effect of doxorubicin (Dox) on human coronary MV function. To study the effect of CT on the cardiac MV function, flow-mediated dilation (FMD), pharmacologically-induced endothelial dependent dilation to acetylcholine (ACh), and smooth muscle-dependent dilation to papaverine were investigated. Vessels were freshly isolated from atrial appendages of adult patients undergoing cardiopulmonary bypass surgery or from cardiac tissue of pediatric patients, collected at the time of surgery to repair congenital heart defects. Isolated vessels were incubated in endothelial culture medium containing vehicle or Dox (100 nm, 15–20 h) and used to measure dilator function by video microscopy. Ex vivo treatment of adult human coronary microvessels with Dox significantly impaired flow-mediated dilation (FMD). Conversely, in pediatric coronary microvessels, Dox-induced impairment of FMD was significantly reduced in comparison with adult subjects. In both adult and pediatric coronary microvessels, ACh-induced constriction was reversed into dilation in the presence of Dox. Smooth muscle-dependent dilation remained unchanged in all groups tested. In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared with adults after anthracycline therapy. NEW & NOTEWORTHY We have characterized, for the first time, human microvascular responses to acute ex vivo exposure to doxorubicin in coronary vessels from patients without cancer. Our data show an augmented impairment of endothelial function in vessels from adult subjects compared with pediatric samples.

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Section: Discussionmentioning

confidence: 99%

Detrimental effects of chemotherapy on human coronary microvascular function

Hader

Zinkevich

Toro

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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“…MSNA was measured for 15 minutes using the microneurography technique as described previously. 15 , 16 …”

Section: Methodsmentioning

confidence: 99%

Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae

et al. 2023

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BACKGROUND: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. METHODS: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. RESULTS: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e′ ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. CONCLUSIONS: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.

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“…Other investigators reported a decrease in brachial artery diameters in patients with gastric and colorectal carcinoma treated with 5‐FU [41]. A recent study from our group showed that one session of adjuvant chemotherapy acutely increases sympathetic nerve activity and vascular resistance in patients with breast cancer [42]. However, because we analyzed before and after the chemotherapy treatment, the information about acute responses to the drug is not available in our study.…”

Section: Discussionmentioning

confidence: 95%

“…Some cardio‐ and neurotoxic adverse events may occur during the infusion of these drugs. In a recent study, we found that acutely chemotherapy infusion provoked an increase in sympathetic nerve activity, vascular resistance, and blood pressure [42]. Our study was designed to investigate the impact of a whole series of adjuvant chemotherapy with 5‐FU or 5‐FU + oxaliplatin on cardiac function, neurovascular responses, and physical capacity in patients with colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Treatment with 5-Fluorouracil and Oxaliplatin Does Not Influence Cardiac Function, Neurovascular Control, and Physical Capacity in Patients with Colon Cancer

et al. 2020

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Background. Adjuvant chemotherapy with 5-fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma. It is known that these drugs have been associated with cardio-and neurotoxicity. We investigated the effects of 5-FU AE oxaliplatin on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. Methods. Twenty-nine patients with prior colectomy for stage II-III adenocarcinoma and clinical indication for adjuvant chemotherapy were allocated to receive 5-FU (n = 12) or 5-FU + oxaliplatin (n = 17), according to the oncologist's decision. All the analyses were performed just before and after the end of chemotherapy. Cardiac function was assessed by echocardiography and speckle tracking, and cardiac autonomic control was assessed by heart rate variability (HRV). Vascular endothelial function was assessed by flowmediated dilation (FMD). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique, and muscle blood flow by venous occlusion plethysmography. Physical capacity was evaluated by cardiopulmonary exercise test. Results. Chemotherapy (pooled data) did not significantly change left ventricular ejection fraction (58 AE 1 vs. 55 AE 2%, p = .14), longitudinal strain (−18 AE 1 vs. −18 AE 1%, p = .66), and HRV. Likewise, chemotherapy did not significantly change FMD, muscle blood flow, and MSNA (33 AE 2 vs. 32 AE 1 bursts/min, p = .31). Physical capacity was not significantly changed in both groups. Similar findings were observed when the patients were subdivided in 5-FU and 5-FU + oxaliplatin treatment groups. 5-FU and 5-FU + oxaliplatin did not significantly change cardiac function, HRV, vascular responses, MSNA, and physical capacity. Conclusion. This study provides evidence that adjuvant treatment with 5-FU AE oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity.

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

Cited by 17 publications

References 50 publications

Detrimental effects of chemotherapy on human coronary microvascular function

Detrimental effects of chemotherapy on human coronary microvascular function

Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae

Adjuvant Treatment with 5-Fluorouracil and Oxaliplatin Does Not Influence Cardiac Function, Neurovascular Control, and Physical Capacity in Patients with Colon Cancer

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