Jacob T. Caldwell

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

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 V˙O2 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/V˙O2) and [HHb] (Δ[HHb]/ΔV˙O2) relative to ΔV˙O2 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, V˙O2 and O2 delivery during exercise.

Effect of exercise‐induced muscle damage on vascular function and skeletal muscle microvascular deoxygenation

This paper investigated the effects of unaccustomed eccentric exercise‐induced muscle damage (EIMD) on macro‐ and microvascular function. We tested the hypotheses that resting local and systemic endothelial‐dependent flow‐mediated dilation (FMD) and microvascular reactivity would decrease, V˙O2max would be altered, and that during ramp exercise, peripheral O2 extraction, evaluated via near‐infrared‐derived spectroscopy (NIRS) derived deoxygenated hemoglobin + myoglobin ([HHb]), would be distorted following EIMD. In 13 participants, measurements were performed prior to (Pre) and 48 h after a bout of knee extensor eccentric exercise designed to elicit localized muscle damage (Post). Flow‐mediated dilation and postocclusive reactive hyperemic responses measured in the superficial femoral artery served as a measurement of local vascular function relative to the damaged tissue, while the brachial artery served as an index of nonlocal, systemic, vascular function. During ramp‐incremental exercise on a cycle ergometer, [HHb] and tissue saturation (TSI%) in the m. vastus lateralis were measured. Superficial femoral artery FMD significantly decreased following EIMD (pre 6.75 ± 3.89%; post 4.01 ± 2.90%; P < 0.05), while brachial artery FMD showed no change. The [HHb] and TSI% amplitudes were not different following EIMD ([HHb]: pre, 16.9 ± 4.7; post 17.7 ± 4.9; TSI%: pre, 71.0 ± 19.7; post 71.0 ± 19.7; all P > 0.05). At each progressive increase in workload (i.e., 0–100% peak), the [HHb] and TOI% responses were similar pre‐ and 48 h post‐EIMD (P > 0.05). Additionally, V˙O2max was similar at pre‐ (3.0 ± 0.67 L min−1) to 48 h post (2.96 ± 0.60 L min−1)‐EIMD (P > 0.05). Results suggest that moderate eccentric muscle damage leads to impaired local, but not systemic, macrovascular dysfunction.