Lower endothelium-dependent microvascular function in adult breast cancer patients receiving radiation therapy.

PURPOSE: Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined. MATERIALS AND METHODS: Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer. Measurements were performed at the site of radiation treatment and at a contralateral control, non-radiated site. Cutaneous vascular conductance (CVC) was calculated by normalizing for mean arterial pressure. RESULTS AND CONCULSIONS: In part 1, patients received an average radiation dose of 2104 ± 236 cGy. A significantly lower peak ACh-mediated endothelium-dependent vasodilation was observed within the radiated microvasculature when compared to non-radiated (radiated: 532 ± 167%, non-radiated 1029 ± 263%; P = 0.02). In part 2, the average radiation dose received was 2251 ± 196 cGy. Iontophoresis of SNP elicited a similar peak endothelium-independent vasodilator response in radiated and non-radiated tissue (radiated: 179 ± 58%, non-radiated: 310 ± 158; P = 0.2). The time to 50% of the peak response for ACh and SNP was similar between radiated and non-radiated microvasculature (P < 0.05). These data provide evidence of early endothelium-dependent microvascular dysfunction in cancer patients currently receiving chest radiation and provide the scientific premise for future work evaluating coronary endothelial function and vasomotor reactivity using more detailed and invasive procedures.

Impact of high sodium intake on blood pressure and functional sympatholysis during rhythmic handgrip exercise.

High dietary sodium intake is a risk factor for arterial hypertension; given that the ability to overcome sympathetically mediated vasoconstriction (functional sympatholysis) is attenuated in individuals with hypertension, we investigated the cardiovascular responses to high salt (HS) intake in healthy humans. We hypothesized that a HS intake of 15 g/day for 7 days would attenuate functional sympatholysis and augment the blood pressure response to handgrip exercise (HGE). Thirteen participants (6 males, 7 females) underwent 2 individual days of testing. Beat-by-beat blood pressure and heart rate were recorded throughout the trial on the non-exercising limb. Forearm blood flow was derived from ultrasonography on the brachial artery of the exercising limb. Participants then underwent a flow-mediated dilation (FMD) test. Next, a submaximal HGE was performed for 7 min with lower body negative pressure initiated during minutes 5-7. A single spot urine sample revealed a significant increase in sodium excretion during the HS conditions (p < 0.01). FMD was reduced during the HS condition. Mean arterial pressure was significantly higher during HS intake. No alteration to functional sympatholysis was found between conditions (p > 0.05). In summary, HS intake increases blood pressure without impacting functional sympatholysis or blood pressure responsiveness during HGE. These findings indicate that brachial artery dysfunction precedes an inefficient functional sympatholysis. Novelty Functional sympatholysis was not impacted by 1 week of high sodium intake. High sodium intake augmented the rate pressure product during handgrip exercise in healthy humans.

Microvascular blood flow during vascular occlusion tests assessed by diffuse correlation spectroscopy.

NEW FINDINGS: What is the central question of this study? What are the characteristics of the time courses of blood flow in the brachial artery and microvascular beds of the skin and skeletal muscle following transient ischaemia? What is the main finding and its importance? Skeletal muscle blood flow was significantly slower than the transient increase in the cutaneous tissue, suggesting mechanistic differences between cutaneous and muscular blood flow distribution after transient ischaemia. These results challenge the use of the cutaneous circulation as globally representative of vascular function. ABSTRACT: Vascular function can be assessed by measuring post-occlusion hyperaemic responses along the arterial tree (vascular occlusion test; VOT). It is currently unclear if responses are similar across vascular beds following cuff release, given potential differences in compliance. To examine this, we compared laser Doppler-derived blood flux in the cutaneous circulation (LDFcut ) and skeletal muscle microvascular blood flux (BFI) using diffuse correlation spectroscopy (DCS), to brachial artery blood flow (BABF) during VOT. We hypothesized that during a VOT following cuff release, (1) BFI response would be delayed compared to the brachial artery response, and (2) time to peak blood flux in the cutaneous vasculature would be slower than both brachial artery and skeletal muscle responses. Seven healthy men (26 ± 4 years) performed three trials of a brachial artery VOT protocol with 10 min of rest between trials. A combined DCS and near-infrared spectroscopy probe provided BFI and oxygenation characteristics (total-[haem]), respectively, of skeletal muscle. BABF was determined via Doppler ultrasound and microvascular cutaneous blood flux was determined via LDFcut . Following cuff release, time to peak of BFI (32.3 ± 6.0 s) was significantly longer than BABF (7.3 ± 2.5 s), LDFcut (10.0 ± 6.4 s) and total-[haem] (14.2 ± 8.3 s) (all P < 0.001). However, time to peak of BABF, LDFcut and total-[haem] were not significantly different (P > 0.05). These results suggest mechanistic differences in control of cutaneous and muscular blood flow distribution after transient ischaemia.

Prediction of Emergency Capsule Egress Performance.

INTRODUCTION: Critical mission tasks for Martian exploration have been identified and include specific duties that astronauts will have to perform despite any adverse effects of chronic microgravity. Specifically, astronauts may have to perform an emergency capsule egress upon return to Earth, which places specific demands on compromised cardiovascular and neuromuscular systems. Therefore, the purpose of this project was to determine the relationship between cardiorespiratory fitness and simulated capsule egress time.METHODS: There were 15 subjects who volunteered for this study. Vo2peak and peak power output (PPO) were determined on cycle and rowing ergometers. Critical power (CP) was determined by a 3-min all-out rowing test. Subjects then performed an emergency capsule egress on a mock-up of NASA's Orion space capsule. Peak metabolic data were compared between the cycling and rowing tests. Pearson's correlation was used to identify relationships between egress time and Vo2peak, PPO, and CP.RESULTS: Vo2peak, Vco2peak, and minute ventilation were not different between cycling and rowing tests. Cycling elicited a greater PPO than the rowing test. Egress time was negatively correlated to rowing PPO (r = -0.60), but not cycling or rowing Vo2peak, cycling PPO, or CP.CONCLUSIONS: Rowing PPO/kg correlates with egress time. Although individuals with higher PPO/kg were able to finish the task in less time, individuals with low fitness levels (Vo2peak ≤ 20 ml · kg-1 · min-1) could complete the egress within 2 mins. These results suggest that cardiorespiratory fitness should not limit emergency egress and that this can be assessed using rowing exercise.Alexander AM, Sutterfield SL, Kriss KN, Hammer SM, Didier KD, Cauldwell JT, Dzewaltowski AC, Barstow TJ, Ade CJ. Prediction of emergency capsule egress performance. Aerosp Med Hum Perform. 2019; 90(9):782-787.

Prediction of Planetary Mission Task Performance for Long-Duration Spaceflight.

INTRODUCTION: This study aimed to determine values and ranges for key aerobic fitness variables that can individually map the level of success for planetary mission tasks performance for long-duration spaceflight, with the goal to develop a predictor-testing model that can be performed with in-flight equipment. METHODS: We studied a group of 45 men and women who completed a series of mission-critical tasks: a surface traverse task and a hill climb task. Participants performed each mission task at a low and moderate intensity designed to elicit specific metabolic responses similar to what is expected for ambulation in lunar and Martian gravities, respectively. Aerobic fitness was characterized via cycling and rowing V˙O2peak, ventilatory threshold (VT), and critical power. Logistic regression and receiver operating characteristic curve analysis were used to determine the cutoff thresholds for each aerobic fitness parameter that accurately predicted task performance. RESULTS: The participants of this study were characterized by a range of cycling V˙O2peak from 15.5 to 54.1 mL·kg·min. A V˙O2peak optimal cutoff values of X and Y mL·kg·min were identified for the low- and moderate-intensity surface traverse tasks, respectively. For the low- and moderate-intensity hill climb test, the optimal V˙O2peak cutoff values were X and Y mL·kg·min, respectively. VT and critical power also showed high sensitivity and specificity for identifying individuals who could not complete the mission tasks. CONCLUSION: In summary, we identified aerobic fitness thresholds below which task performance was impaired for both low- and moderate-intensity mission-critical tasks. In particular, cycling V˙O2peak, VT, and rowing CP could each be used to predict task failure.

Impact of Acute Dietary Nitrate Supplementation during Exercise in Hypertensive Women.

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; 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.

Vasoconstrictor responsiveness through alterations in relaxation time and metabolic rate during rhythmic handgrip contractions.

Increasing the relaxation phase of the contraction-relaxation cycle will increase active skeletal muscle blood flow ( Q˙m ). However, it remains unknown if this increase in Q˙m alters the vasoconstriction responses in active skeletal muscle. This investigation determined if decreasing mechanical impedance would impact vasoconstriction of the active skeletal muscle. Eight healthy men performed rhythmic handgrip exercise under three different conditions; "low" duty cycle at 20% maximal voluntary contraction (MVC), "low" duty cycle at 15% MVC, and "high" duty cycle at 20% MVC. Relaxation time between low and high duty cycles were 2.4 sec versus 1.5 sec, respectively. During steady-state exercise lower body negative pressure (LBNP) was used to evoke vasoconstriction. Finger photoplethysmography and Doppler ultrasound derived diameters and velocities were used to measure blood pressure, forearm blood flow (FBF: mL min-1 ) and forearm vascular conductance (FVC: mL min-1  mmHg) throughout testing. The low duty cycle increased FBF and FVC versus the high duty cycle under steady-state conditions at 20% MVC (P < 0.01). The high duty cycle had the greatest attenuation in %ΔFVC (-1.9 ± 3.8%). The low duty cycle at 20% (-13.3 ± 1.4%) and 15% MVC (-13.1 ± 2.5%) had significantly greater vasoconstriction than the high duty cycle (both: P < 0.01) but were not different from one another (P = 0.99). When matched for work rate and metabolic rate ( V˙O2 ), the high duty cycle had greater functional sympatholysis than the low duty cycle. However, despite a lower V˙O2 , there was no difference in functional sympatholysis between the low duty cycle conditions. This may suggest that increases in Q˙m play a role in functional sympatholysis when mechanical compression is minimized.

Vascular and autonomic changes in adult cancer patients receiving anticancer chemotherapy.

Chemotherapy is associated with acute and long-term cardiotoxicity. To date, risk assessment has primarily focused on the heart; however, recent findings suggest that vascular and autonomic function may also be compromised. Whether this occurs during chemotherapy treatment remains unknown. Therefore, the present study evaluated carotid artery stiffness, cardiovagal baroreflex sensitivity (cBRS), and heart rate variability (HRV) in cancer patients currently being treated with adjuvant chemotherapy. Eleven current cancer patients receiving adjuvant chemotherapy and 11 matched (1:1) controls were studied. Carotid artery stiffness was assessed via two-dimensional ultrasonography. cBRS was assessed from the spontaneous changes in beat-to-beat time series of R-R interval and systolic blood pressure via the cross-correlation technique. HRV was assessed using the standard deviation of R-R intervals (SDNN) and low (LF) and high (HF) power frequencies. Carotid artery ß-stiffness was significantly higher in the cancer patients compared with control participants (8.0 ± 0.8 vs. 6.3 ± 0.6 U, respectively; P = 0.02). cBRS was lower in the cancer patients compared with controls (4.3 ± 0.7 vs. 10.7 ± 1.9 ms/mmHg, respectively; P = 0.01), and all indices of HRV were lower in the cancer patients (SDNN, P = 0.02; LF, P = 0.01; HF, P = 0.02). There was no significant correlation between ß-stiffness and cBRS ( P = 0.4). However, LF power was significantly correlated with cBRS (r = 0.66, P < 0.001). Compared with matched healthy controls, cancer patients undergoing chemotherapy demonstrated a significantly higher arterial stiffness and lower cBRS. The previously reported adverse effects of chemotherapy on the heart appear to also influence other aspects of cardiovascular health. NEW & NOTEWORTHY Patients treated with anticancer chemotherapy exhibit an impaired baroreflex control of arterial blood pressure and increased arterial stiffness. These findings hold significant value, in particular as part of a risk-stratification strategy in current cancer patients receiving chemotherapy. This is the first investigation, to our knowledge, to demonstrate an attenuated spontaneous baroreflex control of arterial blood pressure in cancer patients currently undergoing chemotherapy.

The noninvasive simultaneous measurement of tissue oxygenation and microvascular hemodynamics during incremental handgrip exercise.

Limb blood flow increases linearly with exercise intensity; however, invasive measurements of muscle microvascular blood flow during incremental exercise have demonstrated submaximal plateaus. We tested the hypotheses that 1) brachial artery blood flow (Q̇BA) would increase with increasing exercise intensity until task failure, 2) blood flow index of the flexor digitorum superficialis (BFIFDS) measured noninvasively via diffuse correlation spectroscopy would plateau at a submaximal work rate, and 3) muscle oxygenation characteristics (total-[heme], deoxy-[heme], and percentage saturation) measured noninvasively with near-infrared spectroscopy would demonstrate a plateau at a similar work rate as BFIFDS. Sixteen subjects (23.3 ± 3.9 yr, 170.8 ± 1.9 cm, 72.8 ± 3.4 kg) participated in this study. Peak power (Ppeak) was determined for each subject (1.8 ± 0.4 W) via an incremental handgrip exercise test. Q̇BA, BFIFDS, total-[heme], deoxy-[heme], and percentage saturation were measured during each stage of the exercise test. On a subsequent testing day, muscle activation measurements of the FDS (RMSFDS) were collected during each stage of an identical incremental handgrip exercise test via electromyography from a subset of subjects ( n = 7). Q̇BA increased with exercise intensity until the final work rate transition ( P < 0.05). No increases in BFIFDS or muscle oxygenation characteristics were observed at exercise intensities greater than 51.5 ± 22.9% of Ppeak. No submaximal plateau in RMSFDS was observed. Whereas muscle activation of the FDS increased until task failure, noninvasively measured indices of perfusive and diffusive muscle microvascular oxygen delivery demonstrated submaximal plateaus. NEW & NOTEWORTHY Invasive measurements of muscle microvascular blood flow during incremental exercise have demonstrated submaximal plateaus. We demonstrate that indices of perfusive and diffusive microvascular oxygen transport to skeletal muscle, measured completely noninvasively, plateau at submaximal work rates during incremental exercise, even though limb blood flow and muscle recruitment continued to increase.

Left ventricular strain rate is reduced during voluntary apnea in healthy humans.

During an apneic event, sympathetic nerve activity increases resulting in subsequent increases in left ventricular (LV) afterload and myocardial work. It is unknown how cardiac mechanics are acutely impacted by the increased myocardial work during an apneic event. Ten healthy individuals (23 ± 3 yr) performed multiple voluntary end-expiratory apnea (VEEA) maneuvers exposed to room air, while a subset ( n = 7) completed multiple VEEA exposed to hyperoxic air (100% [Formula: see text]). Beat-by-beat blood pressure, heart rate, and stroke volume were measured continuously. Effective arterial elastance (EA) was calculated as an index of cardiac afterload, and myocardial work was calculated as the rate pressure product (RPP). Tissue Doppler echocardiography was used to measure LV tissue velocities, deformation via strain, and strain rate (SR). Systolic blood pressure (Δ18 ± 13 mmHg, P < 0.01), EA (Δ0.13 ± 0.10 mmHg/ml, P < 0.01), and RPP (Δ9 ± 10 beats/min × mmHg 10-2, P < 0.01) significantly increased with room air VEEA. This occurred in parallel with decreases in peak longitudinal systolic (Δ-0.62 ± 0.41 cm/s, P < 0.01) and early LV filling (Δ-2.81 ± 1.99 cm/s, P < 0.01) myocardial velocities. Longitudinal SR (Δ-0.30 ± 0.32 1/s, P = 0.01) was significantly decreased during room air VEEA. VEEA with hyperoxia did not alter ( P > 0.18) EA or RPP and attenuated the systolic blood pressure response compared with room air. Myocardial velocities and LV strain rate response to VEEA were unchanged ( P = 0.30) with hyperoxia. Consistent with our hypotheses, VEEA-induced increases in EA and myocardial work impact LV mechanics, which may depend, in part, on stimulation of peripheral chemoreceptors. NEW & NOTEWORTHY Transient increases in arterial blood pressure and systemic vascular resistance occur during sleep apnea events and may contribute to the associated daytime hypertension and risk of overt cardiovascular disease. To date, the link between this apnea pressor response and acute changes in left ventricular function remains poorly understood. We demonstrate that in parallel to increases in cardiac afterload a depressed left ventricular systolic function occurs at end apnea.

Exercise-Induced Hypoalgesia Is Not Influenced by Physical Activity Type and Amount.

Physical activity (PA), especially vigorous-intensity PA, has been shown to be related to pain sensitivity. The relationship among PA levels and PA types on endogenous pain inhibition after exercise, termed exercise-induced hypoalgesia (EIH), remains unclear. PURPOSE: This studied examined the EIH response to pressure stimuli among college-age women of differing activity levels. METHODS: Fifty women were tested. Pressure pain threshold (PPT) values were assessed before and immediately after isometric handgrip exercise to exhaustion in the right and left forearms. Participant's PA levels were assessed by wearing an accelerometer for seven consecutive days during waking hours, excluding water activities. Participants were classified into four PA groups: met the American College of Sports Medicine aerobic recommendations (AERO), met aerobic and resistance training recommendations (AERO + RT), insufficiently aerobically active but resistance trained (RT), and insufficiently active (IA) based on their measured and self-reported PA level and type. RESULTS: AERO and AERO + RT had greater vigorous (P < 0.001) and total PA (P < 0.001) compared with RT and IA. EIH was observed for PPT in both right and left arms (P < 0.001), with PPT increasing 7.7% (529 ± 236 vs 569 ± 235 kPa) and 7.0% (529 ± 299 vs 571 ± 250 kPa) in the right and left forearms, respectively. EIH did not differ among activity groups (P = 0.82). PPT values were found to be inversely related to vigorous-intensity PA (r = -0.29). CONCLUSIONS: PA levels and types had no effect on endogenous pain inhibition after exercise in college-age women.