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.

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.

Exercise tolerance through severe and extreme intensity domains.

The power-duration relationship accurately predicts exercise tolerance for constant power exercise performed in the severe intensity domain. However, the accuracy of the prediction of time to task failure (Tlim ) is currently unclear for work rates (WR) above severe intensities; that is, within the extreme intensity domain (Tlim  < 2 min). We hypothesized that Tlim would be shorter for WRs within the extreme intensity domain than predicted from the linear 1/time relationship of the severe intensity domain which would suggest mechanisms limiting exercise are different between intensity domains. Six men completed 7 knee-extension tests. Tlim of extreme intensity exercise (60%, 70%, 80%, and 90% 1RM; Tlim  < 2 min) were compared to the predicted Tlim from the slope of the S1-S3 (Tlim  ≥ 2-15 min) regression. Twitch force (Qtw ) and maximal voluntary contraction (MVC) were measured on the right vastus lateralis before and after each test. Tlim at 70-90% 1RM were shorter than the Tlim predicted by the severe domain 1/time model (P < 0.05); however, Tlim at 60% 1RM was not different than the predicted severe Tlim , suggesting the mechanisms limiting extreme exercise manifest ≥60% 1RM. A significant linear relationship for 60-90% 1RM was observed which suggested a curvature constant unique to the extreme domain ( Wext' ) that was smaller than the W ' of the severe domain (1.5 ± 0.6 vs. 5.9 ± 1.5 kJ, P < 0.001). Qtw and MVC were significantly decreased following severe exercise, however, Qtw and MVC were not significantly decreased following 80% and 90% 1RM, giving evidence that mechanisms causing task failure were recovered by the time post-exercise measurements were made (~90 sec).

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.

Older women exhibit greater airway 8-isoprostane responses to strenuous exercise compared with older men and younger controls.

Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%-75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC (p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases.