Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation

Austin K Ederer, Kaylin D Didier, Landon K Reiter, Michael Brown, Rachel Hardy, Jacob Caldwell, Christopher D Black, Rebecca D Larson, Carl J Ade, Austin K Ederer, Kaylin D Didier, Landon K Reiter, Michael Brown, Rachel Hardy, Jacob Caldwell, Christopher D Black, Rebecca D Larson, Carl J Ade

Abstract

The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (ΔTOIΔ/V̇O2) and [HHb] (Δ[HHb]/ΔV̇O2) relative to ΔV̇O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Endothelium-dependent, flow-mediated, brachial artery dilation…
Fig 1. Endothelium-dependent, flow-mediated, brachial artery dilation (FMD) in control and cancer survivors (CS).
FMD values are shown normalized for the magnitude of the hyperaemic shear stimulus (i.e. % change in diameter divided by the AUCSR).
Fig 2. Near-infrared spectroscopy (NIRS)-obtained muscle oxygenation…
Fig 2. Near-infrared spectroscopy (NIRS)-obtained muscle oxygenation data at baseline, 50 W, and the ventilatory threshold (VT).
Tissue oxygenation index (TOI; Panel A) in the cancer survivors remained at baseline levels throughout the test compared to the progressive decrease observed in controls. Deoxygenated hemoglobin ([HHb]; Panel B) was significantly lower in cancer survivors compared to controls at VT. Total hemoglobin ([Hb]total; Panel C) at VT was significantly decreased in the cancer survivors compared to controls. Values are mean ± SE; † P<0.05 significantly different compared to baseline. * P<0.05 significantly different compared to controls.
Fig 3. The rate of change for…
Fig 3. The rate of change for tissue oxygenation index (TOI; Panel A), deoxygenated hemoglobin ([HHb]; Panel B), and total hemoglobin ([Hb]total; Panel C) as a function of oxygen uptake (V˙O2).
Note that the absolute change in TOI and [HHb] as a function of the increase V˙O2 during exercise were significantly less in cancer survivors compared to controls. Values are mean ± SE.

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