Neurovascular dysfunction associated with erectile dysfunction persists after long-term recovery from simulations of weightlessness and deep space irradiation.

There has been growing interest within the space industry for long-duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long-term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty-six adult male Fisher-344 rats were randomized into six groups and exposed to 4-weeks of hindlimb unloading (HLU) or weight-bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground-based GCR simulator at the NASA Space Radiation Laboratory. Following a 12-13-month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium-dependent and -independent relaxation that was tissue type specific. GCR impaired non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation in the dIPA and CC, while follow-up experiments of the CC showed restoration of NANC-mediated relaxation of GCR tissues following acute incubation with the antioxidants mito-TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long-term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.

Inorganic nitrate supplementation may improve diastolic function and the O2 cost of exercise in cancer survivors: a pilot study.

In non-cancer populations, inorganic dietary nitrate (NO3-) supplementation is associated with enhanced cardiorespiratory function but remains untested in patients with a history of cancer. Therefore, this pilot study sought to determine if oral NO3- supplementation, as a supportive care strategy, increases left ventricular (LV) function and exercise performance in survivors of cancer treated with anticancer therapy while simultaneously evaluating the feasibility of the methods and procedures required for future large-scale randomized trials. Two cohorts of patients with a history of cancer treated with anticancer chemotherapy were recruited. Patients in cohort 1 (n = 7) completed a randomized, double-blind, crossover study with 7 days of NO3- or placebo (PL) supplementation, with echocardiography. Similarly, patients in cohort 2 (n = 6) received a single, acute dose of NO3- supplementation or PL. Pulmonary oxygen uptake (VO2), arterial blood pressure, and stroke volume were assessed during exercise. In cohort 1, NO3- improved LV strain rate in early filling (mean difference (MD) [95% CI]: - 0.3 1/s [- 0.6 to 0.06]; P = 0.04) and early mitral septal wall annular velocity (MD [95% CI]: 0.1 m/s [- 0.01 to - 0.001]; P = 0.02) compared to placebo. In cohort 2, NO3- decreased the O2 cost of low-intensity steady-state exercise (MD [95% CI]: - 0.5 ml/kg/min [- 0.9 to - 0.09]; P = 0.01). Resting and steady-state arterial blood pressure and stroke volume were not different between conditions. No differences between conditions for peak VO2 (MD [95% CI]: - 0.7 ml/kg/min [- 3.0 to 1.6]; P = 0.23) were observed. The findings from this pilot study warrant further investigation in larger clinical trials targeting the use of long-term inorganic dietary NO3- supplementation as a possible integrative supportive care strategy in patients following anticancer therapy.

Aerobic exercise training reduces cardiac function and coronary flow-induced vasodilation in mice lacking adiponectin.

We tested the hypothesis that adiponectin deficiency attenuates cardiac and coronary microvascular function and prevents exercise training-induced adaptations of the myocardium and the coronary microvasculature in adult mice. Adult wild-type (WT) or adiponectin knockout (adiponectin KO) mice underwent treadmill exercise training or remained sedentary for 8-10 wk. Systolic and diastolic functions were assessed before and after exercise training or cage confinement. Vasoreactivity of coronary resistance arteries was assessed at the end of exercise training or cage confinement. Before exercise training, ejection fraction and fractional shortening were similar in adiponectin KO and WT mice, but isovolumic contraction time was significantly lengthened in adiponectin KO mice. Exercise training increased ejection fraction (12%) and fractional shortening (20%) with no change in isovolumic contraction time in WT mice. In adiponectin KO mice, both ejection fraction (-9%) and fractional shortening (-12%) were reduced after exercise training and these decreases were coupled to a further increase in isovolumic contraction time (20%). In sedentary mice, endothelium-dependent dilation to flow was higher in arterioles from adiponectin KO mice as compared with WT mice. Exercise training enhanced dilation to flow in WT mice but decreased flow-induced dilation in adiponectin KO mice. These data suggest that compensatory mechanisms contribute to the maintenance of cardiac and coronary microvascular function in sedentary mice lacking adiponectin; however, in the absence of adiponectin, cardiac and coronary microvascular adaptations to exercise training are compromised.NEW & NOTEWORTHY We report that compensatory mechanisms contribute to the maintenance of cardiac and coronary microvascular function in sedentary mice in which adiponectin has been deleted; however, when mice lacking adiponectin are subjected to the physiological stress of exercise training, beneficial coronary microvascular and cardiac adaptations are compromised or absent.

Vascular ATP-sensitive K+ channels support maximal aerobic capacity and critical speed via convective and diffusive O2 transport.

KEY POINTS: Oral sulphonylureas, widely prescribed for diabetes, inhibit pancreatic ATP-sensitive K+ (KATP ) channels to increase insulin release. However, KATP channels are also located within vascular (endothelium and smooth muscle) and muscle (cardiac and skeletal) tissue. We evaluated left ventricular function at rest, maximal aerobic capacity ( V̇ O2 max) and submaximal exercise tolerance (i.e. speed-duration relationship) during treadmill running in rats, before and after systemic KATP channel inhibition via glibenclamide. Glibenclamide impaired critical speed proportionally more than V̇ O2 max but did not alter resting cardiac output. Vascular KATP channel function (topical glibenclamide superfused onto hindlimb skeletal muscle) resolved a decreased blood flow and interstitial PO2 during twitch contractions reflecting impaired O2 delivery-to-utilization matching. Our findings demonstrate that systemic KATP channel inhibition reduces V̇ O2 max and critical speed during treadmill running in rats due, in part, to impaired convective and diffusive O2 delivery, and thus V̇ O2 , especially within fast-twitch oxidative skeletal muscle. ABSTRACT: Vascular ATP-sensitive K+ (KATP ) channels support skeletal muscle blood flow and microvascular oxygen delivery-to-utilization matching during exercise. However, oral sulphonylurea treatment for diabetes inhibits pancreatic KATP channels to enhance insulin release. Herein we tested the hypotheses that: i) systemic KATP channel inhibition via glibenclamide (GLI; 10 mg kg-1 i.p.) would decrease cardiac output at rest (echocardiography), maximal aerobic capacity ( V̇ O2 max) and the speed-duration relationship (i.e. lower critical speed (CS)) during treadmill running; and ii) local KATP channel inhibition (5 mg kg-1 GLI superfusion) would decrease blood flow (15 µm microspheres), interstitial space oxygen pressures (PO2 is; phosphorescence quenching) and convective and diffusive O2 transport ( Q̇ O2 and DO2 , respectively; Fick Principle and Law of Diffusion) in contracting fast-twitch oxidative mixed gastrocnemius muscle (MG: 9% type I+IIa fibres). At rest, GLI slowed left ventricular relaxation (2.11 ± 0.59 vs. 1.70 ± 0.23 cm s-1 ) and decreased heart rate (321 ± 23 vs. 304 ± 22 bpm, both P < 0.05) while cardiac output remained unaltered (219 ± 64 vs. 197 ± 39 ml min-1 , P > 0.05). During exercise, GLI reduced V̇ O2 max (71.5 ± 3.1 vs. 67.9 ± 4.8 ml kg-1 min-1 ) and CS (35.9 ± 2.4 vs. 31.9 ± 3.1 m min-1 , both P < 0.05). Local KATP channel inhibition decreased MG blood flow (52 ± 25 vs. 34 ± 13 ml min-1 100 g tissue-1 ) and PO2 isnadir (5.9 ± 0.9 vs. 4.7 ± 1.1 mmHg) during twitch contractions. Furthermore, MG V̇ O2 was reduced via impaired Q̇ O2 and DO2 (P < 0.05 for each). Collectively, these data support that vascular KATP channels help sustain submaximal exercise tolerance in healthy rats. For patients taking sulfonylureas, KATP channel inhibition may exacerbate exercise intolerance.

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.

Central and peripheral factors mechanistically linked to exercise intolerance in heart failure with reduced ejection fraction.

Exercise intolerance is a primary symptom of heart failure (HF); however, the specific contribution of central and peripheral factors to this intolerance is not well described. The hyperbolic relationship between exercise intensity and time to exhaustion (speed-duration relationship) defines exercise tolerance but is underused in HF. We tested the hypotheses that critical speed (CS) would be reduced in HF, resting central functional measurements would correlate with CS, and the greatest HF-induced peripheral dysfunction would occur in more oxidative muscle. Multiple treadmill-constant speed runs to exhaustion were used to quantify CS and D' (distance coverable above CS) in healthy control (Con) and HF rats. Central function was determined via left ventricular (LV) Doppler echocardiography [fractional shortening (FS)] and a micromanometer-tipped catheter [LV end-diastolic pressure (LVEDP)]. Peripheral O2 delivery-to-utilization matching was determined via phosphorescence quenching (interstitial Po2, Po2 is) in the soleus and white gastrocnemius during electrically induced twitch contractions (1 Hz, 8V). CS was lower in HF compared with Con (37 ± 1 vs. 44 ± 1 m/min, P < 0.001), but D' was not different (77 ± 8 vs. 69 ± 13 m, P = 0.6). HF reduced FS (23 ± 2 vs. 47 ± 2%, P < 0.001) and increased LVEDP (15 ± 1 vs. 7 ± 1 mmHg, P < 0.001). CS was related to FS (r = 0.72, P = 0.045) and LVEDP (r = -0.75, P = 0.02) only in HF. HF reduced soleus Po2 is at rest and during contractions (both P < 0.01) but had no effect on white gastrocnemius Po2 is (P > 0.05). We show in HF rats that decrements in central cardiac function relate directly with impaired exercise tolerance (i.e., CS) and that this compromised exercise tolerance is likely due to reduced perfusive and diffusive O2 delivery to oxidative muscles.NEW & NOTEWORTHY We show that critical speed (CS), which defines the upper boundary of sustainable activity, can be resolved in heart failure (HF) animals and is diminished compared with controls. Central cardiac function is strongly related with CS in the HF animals, but not controls. Skeletal muscle O2 delivery-to-utilization dysfunction is evident in the more oxidative, but not glycolytic, muscles of HF rats and is explained, in part, by reduced nitric oxide bioavailability.

Preexercise intermittent passive stretching and vascular function after treadmill exercise.

Acute aerobic exercise stress is associated with decreased endothelial function that may increase the likelihood of an acute cardiovascular event. Passive stretch (PS) elicits improvements in vascular function, but whether PS can be performed before exercise to prevent declines in vascular function remains unknown. This strategy could be directly applicable in populations that may not be able to perform dynamic exercise. We hypothesized that preexercise PS would provide better vascular resilience after treadmill exercise. Sixteen healthy college-aged males and females participated in a single laboratory visit and underwent testing to assess micro- and macrovascular function. Participants were randomized into either PS group or sham control group. Intermittent calf PS was performed by having the foot in a splinting device for a 5-min stretch and 5-min relaxation, repeated four times. Then, a staged V̇o2 peak test was performed and 65% V̇o2 peak calculated for subjects to run at for 30 min. Near-infrared spectroscopy-derived microvascular responsiveness was preserved with the PS group [(pre: 0.53 ± 0.009%/s) (post: 0.56 ± 0.012%/s; P = 0.55)]. However, there was a significant reduction in the sham control group [(pre: 0.67 ± 0.010%/s) (post: 0.51 ± 0.007%/s; P = 0.05)] after treadmill exercise. Flow-mediated vasodilation (FMD) of the popliteal artery showed similar responses. In the PS group, FMD [(pre: 7.23 ± 0.74%) (post: 5.86 ± 1.01%; P = 0.27)] did not significantly decline after exercise. In the sham control group, FMD [(pre: 8.69 ± 0.72%) (post: 5.24 ± 1.24%; P < 0.001)] was significantly reduced after treadmill exercise. Vascular function may be more resilient if intermittent PS is performed before moderate-intensity exercise and, importantly, can be performed by most individuals.NEW & NOTEWORTHY We demonstrate for the first time that popliteal artery and gastrocnemius microvascular responsiveness after acute aerobic exercise are reduced. The decline in vascular function was mitigated in those who performed intermittent passive stretching before the exercise bouts. Collectively, these findings suggest that intermittent passive stretching is a novel method to increase vascular resiliency before aerobic activity.

Effects of high-intensity training on prostate cancer-induced cardiac atrophy.

BACKGROUND: Recent evidence suggests prostate cancer independent of treatment has atrophic effects on whole heart and left ventricular (LV) masses, associated with reduced endurance exercise capacity. In a pre-clinical model, we tested the hypothesis that high-intensity training could prevent cardiac atrophy with prostate cancer and alter cardiac protein degradation mechanisms. METHODS: Dunning R-3327 AT-1 prostate cancer cells (1×105) were injected into the ventral prostate lobe of 5-6 mo immunocompetent Copenhagen rats (n=24). These animals were randomized into two groups, tumor-bearing exercise (TBEX, n=15) or tumor bearing sedentary (TBS, n=9). Five days after surgery, TBEX animals began exercise on a treadmill (25 m/min, 15° incline) for 45-60 min/day for 18±2 days. Pre-surgery (Pre), and post-exercise training (Post) echocardiographic evaluation (Vivid S6, GE Health Care), using the parasternal short axis view, was used to examine ventricle dimensions. Markers of protein degradation (muscle atrophy F-box, Cathepsin B, Cathepsin L) in the left ventricle were semi-quantified via Western Blot. RESULTS: There were no significant differences in tumor mass between groups (TBEX 3.4±0.7, TBS 2.8±0.6 g, P=0.3), or body mass (TBEX 317±5, TBS 333±7 g, P=0.2). Heart-to-body mass ratio was lower in TBS group compared to TBEX (2.3±0.1 vs. 2.5±0.1 mg/g, P<0.05). LV/body mass ratio was also lower in the TBS group (1.6±0.1 vs. 1.8±0.1 mg/g, P<0.05). From Pre-Post, TBEX had significant increases in SV (~20% P<0.05) whereas TBS had no significant change. There were no significant differences between groups for markers of protein degradation. CONCLUSION: This study suggests that high-intensity exercise can improve LV function and increase LV mass concurrent with prostate cancer development, versus sedentary counterparts. Given cardiac dysfunction often manifests with conventional anti-cancer treatments, a short-term high-intensity training program, prior to treatment, may improve cardiac function and fatigue resistance in cancer patients.

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.

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.

Effects of prostate cancer and exercise training on left ventricular function and cardiac and skeletal muscle mass.

Prostate cancer was found to reduce cardiac and left ventricle (LV) masses in association with diminished exercise capacity in rats. We tested the hypothesis that exercise training will mitigate prostate cancer-induced cardiac and skeletal muscle atrophy and improve LV function versus sedentary tumor-bearing counterparts. Copenhagen rats ( n = 39; ~5 mo old) were randomized into four groups: exercise-trained tumor-bearing (EXTB) or control (EXCON) and sedentary tumor-bearing (SEDTB) or control (SEDCON). Dunning R-3327 prostate cancer cells were injected orthotopically in 19 of the 39 animals. Treadmill exercise training was performed for 60 min/day for ~30 days. Animals underwent echocardiography to examine ventricle dimensions "Pre-" cancer injection or exercise (PRE) and 15 (Post 1) and 32-35 (Post 2) days after cancer cell injection with tissues collected after Post 2. LV TNF-α and IL-6 concentrations were measured post mortem. Cardiac and LV mass of SEDTB animals were lower than all groups ( P < 0.05). Tumor mass was negatively correlated with LV mass in EXTB (-0.75, P < 0.02) and SEDTB animals (-0.72, P < 0.02). EXCON group had higher stroke volume Post 2 assessment compared with both sedentary groups ( P < 0.05) but not EXTB animals. No difference in LV [IL-6] or [TNF-α] was found between the cancer groups. The current investigation demonstrates prostate cancer, independent of anticancer treatment, significantly reduces cardiac mass and LV mass as well as locomotor muscle masses. However, moderate-intensity exercise training can mitigate cardiac and skeletal muscle atrophy with prostate cancer and preserve the cardiac phenotype (i.e., mass and function) to that of the healthy sedentary group. NEW & NOTEWORTHY This study demonstrates the atrophic effects of prostate cancer on cardiac and skeletal muscle mass independent of anticancer treatment(s) that can be mitigated with moderate-intensity exercise. These findings have important implications for potentially improving the quality of life as well as therapeutic outcomes for patients with prostate cancer.

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.

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.