Cancer patients with a history of anticancer chemotherapy are at an increased cardiovascular disease risk compared with cancer-free populations. Therefore, we tested the hypothesis that cancer patients receiving adjuvant chemotherapy would have a lower cutaneous microvascular reactivity and lower endothelium-dependent flow-mediated dilation (FMD) of the brachial artery compared with matched cancer-free control subjects. To test this hypothesis, we performed a case control study with seven cancer patients receiving adjuvant chemotherapy and seven matched healthy reference control subjects. Red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry. Acetylcholine (ACh)-mediated vasodilation was determined by iontophoresis. Data were expressed as percent increase in cutaneous vascular conductance. Endothelium-dependent FMD of the brachial artery via ultrasonography was determined as an index of macrovessel endothelial function. Cutaneous microvascular reactivity was attenuated in cancer patients compared with control subjects [cancer: 959.9 ± 187.3%, control: 1,556.8 ± 222.2%; P = 0.03, effect size (ES) = 1.1]. Additionally, cancer patients demonstrated a significantly lower area under the curve response to ACh iontophoresis compared with healthy control subjects. Brachial artery FMD was also significantly lower in cancer patients compared with control subjects (cancer: 2.2 ± 0.6%, control: 6.6 ± 1.4%; P = 0.006, ES = 1.6), which was significantly associated with measurements of microvascular reactivity. These findings suggest that decreases in vascular reactivity can occur during cancer chemotherapy, which may have implications for the long-term risk of cardiovascular disease morbidity and mortality. NEW & NOTEWORTHY Cancer survivors treated with chemotherapy experience an increased risk of cardiovascular events, linked to both cardiac and vascular toxicity. The major finding of this study is that microvascular reactivity and macrovascular endothelium-dependent flow-mediated dilation are lower in cancer patients currently receiving adjuvant chemotherapy compared with healthy counterparts.

Recent studies outlined linear and non-linear dynamics in heart rate variability; however, their physiological origin is still unknown. The present study investigated the impact of cerebral function on linear and non-linear dynamics in heart rate variability. Electrocardiograms from seven brain dead organ donors and seven healthy volunteers were analyzed. Atropine was used in healthy volunteers to adjust their heart rate to that of the donors. As compared to healthy volunteers without atropine, the linear dynamics of heart rate variability, determined by time and frequency domain analyses, were significantly reduced in healthy volunteers with atropine and, to an even greater extent, in donors. Atropine tended to increase the complexity and non-linearity of heart rate variability in healthy volunteers, as determined by the correlation dimension D and the largest Lyapunov exponent L, respectively (D = 9.43 +/- 2.93 vs. 7.65 +/- 0.97 and L = 0.525 +/- 0.099 vs. 0.504 +/- 0.047 bits.beat-1; both NS), while these indices were significantly reduced in donors by 19.5 +/- 12.8% and 15.0 +/- 11.7%, respectively (D = 6.16 +/- 0.98 and L = 0.428 +/- 0.059 bits.beat-1; both p < 0.05 vs. volunteers). Thus, loss of cerebral function reduces both linear and non-linear components of heart rate variability.

Introduction the aim of the current investigation was to examine if dietary nitrate supplementation would improve vascular control in hypertensive postmenopausal women (PMW). We tested the hypotheses that acute dietary nitrate supplementation would 1) significantly decrease arterial blood pressure (BP) at rest and during exercise, 2) increase limb blood flow during steady-state (SS) exercise, and 3) improve functional sympatholysis during SS exercise. Methods Ten hypertensive PMW underwent a randomized, double-blind, placebo-controlled trial with a nitrate-rich (NR) or nitrate-poor (NP) supplement. Beat-by-beat BP and heart rate were recorded throughout the trial on the nonexercising limb. Forearm blood flow was measured via ultrasonography on the brachial artery of the exercising limb. All patients performed a resting cold pressor test (CPT) (2 min) and then 7 min of submaximal handgrip exercise with a CPT applied during minutes 5–7. Results SS systolic (NR, 170 ± 7; NP, 171 ± 37 mm Hg), diastolic (NR, 89 ± 2; NP, 92 ± 2 mm Hg), and mean arterial (NR, 121 ± 4; NP, 123 ± 2 mm Hg) pressures were not different between NP and NR treatment conditions (P > 0.05). During SS exercise, forearm blood flow (NR, 189 ± 8; NP, 218 ± 8 mL·min−1; P = 0.03) in the NR treatment was significantly lower compared with NP. When the CPT was applied during minutes 6–7 of exercise, forearm vascular conductance was reduced by 15% in the NR condition, but only 7% in the NR condition. Conclusions In summary, an acute NR supplement improved functional sympatholysis by ~50% versus an NP placebo condition. Improvements in functional sympatholysis may have important implications regarding exercise tolerance in hypertensive PMW.

High dietary salt intake is associated with an increased risk for the development of hypertension, cardiovascular (CVD) and cerebrovascular disease. Additionally, exaggerated blood pressure during dynamic exercise is independently predictive of future CVD beyond resting blood pressure and other conventional risk factors. This is critical given that in animal models, dietary salt negatively augments blood pressure responses during static hind‐limb contractions, suggesting an increased risk of an adverse CVD event during exercise with high dietary salt. However, it currently remains unknown if high salt intake increases arterial blood pressure and impairs vascular function during voluntary dynamic exercise in healthy men and women. Based on previous preclinical reports, we hypothesized that high salt intake would decrease resting vascular endothelial function, increase arterial blood pressure during dynamic exercise and decrease functional sympatholysis. Thirteen healthy men and women underwent a randomized, double‐blind, placebo‐controlled trial for 7 days with either 15g/day sodium chloride supplement or cellulose. Beat‐by‐beat mean (MAP), systolic (SBP) and diastolic (DBP) were recorded throughout the trial on the non‐exercising limb. Forearm blood flow (FBF) was calculated via mean blood velocity derived from ultrasonography on the brachial artery of the exercising limb. All patients performed a flow‐mediated dilation (FMD) protocol followed by (20% maximal voluntary contraction) submaximal hand‐grip exercise for 7 min with lower‐body negative pressure initiated during min 5 – 7. FMD was significantly reduced during the HS condition (HS: 2.2±0.26e−5; Pl: 4.1±0.56e−5; p<0.01). Compared to placebo, the absolute steady‐state exercise MAP and SBP were significantly higher during HS compared to the placebo condition (p<0.05). However, functional sympatholysis was not different between conditions (p=0.07). In summary, the results of this study show the effects of HS intake on arterial blood pressure during handgrip exercise. These findings highlight that the augmented exercise blood pressures may be key mediator for the increased risk for adverse CVD outcomes associated with high dietary salt intake.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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IntroductionAndrogen‐deprivation therapy (ADT) in prostate cancer has been suggested to promote an unfavorable cardiovascular disease risk profile and long‐term cardiovascular mortality. Impairments in vascular structure (increased arterial stiffness) and function (decreased endothelial‐dependent dilation) are known to occur with ADT, however, it remains unknown if the changes in structure‐function relationship adversely impacts the interaction between ventricular and arterial systems. Ventricular‐arterial coupling is a measure of effective arterial elastance (Ea) and left ventricular end‐systolic elastance (Ees) and is a central determinant of cardiovascular performance and cardiac energetics. Therefore, this study sought to evaluate ventricular‐arterial coupling at rest and during submaximal exercise in prostate cancer patients with and without a history of ADT.MethodsTo date, 7 prostate cancer patients with (n=3) and without (n=4) a history of androgen‐deprivation therapy treatment have completed the study. Ea, Ees, and ventricular‐arterial coupling (Ea/Ees) were measured at rest and during supine submaximal exercise. A high Ea/Ees is reflective of a compromised interaction between ventricular and arterial systems. To minimize the effect of heart rate on each parameter submaximal exercise was performed at a work rate corresponding to a heart rate of 100 beats/min.ResultsAt rest Ea (ADT: 2.9±0.2 mmHg/mL; non‐ADT: 3.4±0.8 mmHg/mL; P=0.2), Ees (ADT: 3.2±1.9 mmHg/mL; non‐ADT: 3.6±0.6 mmHg/mL; P=0.2), and Ea/Ees (ADT: 0.79±0.39; non‐ADT: 0.97±0.30; P=0.5) were similar between ADT and non‐ADT groups. Ea was not different between groups during exercise (ADT: 7.0±1.1 mmHg/mL; non‐ADT: 6.6±0.6 mmHg/mL; P=0.3). Moderate‐intensity exercise‐induced increases in Ees trended to be decreased in the ADT group (ADT: 3.5±1.2 mmHg/mL; non‐ADT: 4.7±0.5 mmHg/mL; P=0.05). Ea/Ees was also higher in the ADT group during exercise compared to the non‐ADT group, but did not reach statistical significance (ADT: 0.93±0.16; non‐ADT: 0.77±0.16; P=0.1).ConclusionsThe findings from this study provide preliminary data that indicates ADT in prostate cancer patients may adversely alter left ventricular end‐systolic elastance during exercise, but does not significantly alter ventricular‐arterial coupling. Additional data will contribute to the evaluation of the interaction between ventricular and arterial systems in patients receiving ADT.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Functional sympatholysis is a well‐known mechanism that blunts the sympathetic vasoconstrictor signal in working muscle, enabling blood flow to be maintained during exercise in the moderate intensity domain. Recent work has demonstrated that exercise intensity and contraction frequency effects functional sympatholysis via changes in metabolic rate. However, less is known about the effects duty cycle (DC) on functional sympatholysis, which alters the time that intramuscular pressure is developed throughout a contraction cycle independent of changes in frequency and intensity. Given that a higher duty cycle (i.e., 50% DC) attenuates muscle blood flow to the working limb, potentially leading to a greater metabolite buildup, we hypothesized that a 20% DC would show greater percent change in forearm vascular conductance (%Δ FVC) and forearm blood flow (%Δ FBF) when compared to 50% duty cycle.METHODSEight healthy male subjects (age: 25 ± 1 yrs; height: 176.8 ± 1.5 cm; weight: 84 ± 5 kg) agreed to participate in the current investigation. Subjects began with a four‐minute resting protocol, two‐minutes of supine blood pressure and blood flow and two‐minutes utilizing lower‐body negative pressure (LBNP; ‐30 mmHg) to increase sympathetic outflow. Subjects then underwent two exercise conditions in a randomized order consisting of 20% and 50% DC (20%:50% or 50%:20%) with ~10 min between trials to allow blood pressure and blood flow to return to baseline. All hand‐grip exercise was performed at 20 contractions per minute at a workload of 20% of subject's maximal voluntary contraction.RESULTSAbsolute FVC during the 20% duty cycle condition was significantly higher than the 50% duty cycle (20%: 398 ± 34; 50%: 327 ± 37 ml min−1 mmHg−1; P < 0.01). FBF was also significantly higher in the 20% duty cycle condition (20%: 392 ± 21; 50%: 330 ± 29 ml min−1; P < 0.01). During steady state hand‐grip exercise coupled with LBNP, %Δ FVC, an indicator of sympathetically‐mediated vasoconstriction, showed a larger percent reduction during 20% duty cycle (20%: −12.6 ± 1.5%; 50%: 1.4 ± 3.9%; P < 0.01).CONCLUSIONThe results of the current investigation suggest that the 20% DC had a greater sympathetically‐mediated vasoconstrictor response compared to the 50% duty cycle.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.