Andrew R. Coggan

We determined the effects of NO ₃ ⁻ ingestion on voluntary and electrically evoked rate of torque development (RTD) in young men and women. Using double-blind, placebo-controlled crossover designs, 14 men or 12 women (tested during both early and late follicular phases) acutely ingested 200 μmol/kg of NO ₃ ⁻ from beetroot juice (BRJ) or a NO ₃ ⁻ -free BRJ placebo. Voluntary RTD (0-30 ms, 0-50 ms, 0-200 ms, maximal) was measured during maximal voluntary isometric contractions. The maximal tetanic RTD was also determined during stimulation at 100 Hz. Muscles tested included the triceps surae and triceps brachii in men and the quadriceps femoris in women. Dietary NO ₃ ⁻ had no significant effect on initial or maximal voluntary RTD in men in either muscle group (P≥0.31) or in women during either menstrual phase (P≥0.69). Similarly, acute NO ₃ ⁻ intake did not alter maximal tetanic RTD in men (P≥0.87) or women (P≥0.70). We conclude that acute dietary NO ₃ ⁻ supplementation has no apparent effect on RTD during maximal voluntary or electrically evoked isometric contractions of the lower or upper limbs in young, untrained individuals. These findings argue against changes in neural activation or actomyosin crossbridge cycling rate as mechanisms driving NO ₃ ⁻ -induced improvements in muscle contractile function.

Changes in metabolic inflexibility were detected during walking at intensities reflecting activities of independent living in sedentary postmenopausal women with overweight/obesity. This work provides evidence for a stronger link between menopausal duration and metabolic inflexibility during walking when compared with chronological age. Our analyses also revealed that RSMI was a key predictor ΔFATox during walking and thus identified it as a clinically relevant, modifiable target for the improvement of cardiometabolic health in future clinical trials.

Introduction/Aims: Voluntary muscle contractions result in a temporary increase in twitch force, a phenomenon termed post activation potentiation (PAP). In rodents and other species, PAP is observed predominantly or exclusively in fast twitch muscles. However, it has been suggested that in humans, PAP occurs more or less independently of muscle fiber type. Methods: Eighteen healthy men and women (27 ± 8 years) underwent an electrical stimulation protocol during which two sets of four twitches were elicited both pre and post 6 s maximal voluntary contractions of the triceps surae (60%–70% slow twitch) and triceps brachii (60%–70% fast twitch) muscles. Results: Unpotentiated peak twitch torque (PTT) was higher in the larger triceps surae versus the smaller triceps brachii (i.e., 13.4 ± 5.3 vs. 3.4 ± 2.1 nm; p < 0.001), but time to peak torque was shorter (i.e., 84 ± 7 vs. 132 ± 14 ms; p < 0.001) and relative rate of torque development (RTD) was greater in the triceps brachii (2294 ± 257 vs. 1425% ± 102%/s; p < 0.001). PAP increased PTT by 172% ± 124% in the triceps brachii versus 20% ± 20% in the triceps surae ( p < 0.001). Absolute RTD also increased more in the triceps brachii (i.e., 240% ± 170% vs. 31% ± 24%; p < 0.001). However, PAP‐induced changes in half‐relaxation time and relative rate of relaxation did not differ between muscle groups. Discussion: We conclude that PAP influences contraction but not relaxation of human muscle in a fiber type dependent manner. This should be kept in mind when interpreting individual differences in the results of neuromuscular testing, response to varying warm‐up protocols, etc.

We determined the effects of dietary [ ] on muscle contractile function during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle. Although [ ] supplementation had no impact on muscle contractility, during electrically evoked twitches, the rate of torque development was greater, and the rate of relaxation was slower, in the LF phase. These findings enhance our understanding of how dietary [ ] and female sex hormones impact muscle contractile function.

Skeletal muscle dysfunction contributes to exercise intolerance in patients with pulmonary arterial hypertension (PAH). Reduced blood flow to skeletal muscle has been demonstrated in a rat model of the disease. We investigated the effect of acute nitrate (NO₃⁻) ingestion via beetroot juice (BRJ) on exercising muscle blood flow, and on plasma and muscle nitrate (NO₃⁻), nitrite (NO₂⁻) and cyclic GMP (cGMP) in male Sprague Dawley rats (~200 g, n=24) with monocrotaline-induced (60 mg/kg) PH. Muscle blood flow was assessed at rest and during treadmill running using fluorescent microspheres. Despite higher plasma NO₃⁻ (756 ± 118 vs 63 ± 22 μmol/L p=2⁻ (0.63 ± 0.10 vs. 0.24 ± 0.04 μmol/L p=0.003), no difference between BRJ and PL was observed in either resting (p=0.88) or exercising (p=0.42) blood flow. Only NO₃⁻ was higher in BRJ vs. PL for both the soleus (sol: 261 ± 20 vs. 123 ± 18 vs μmol/kg, p=2⁻ (sol: 1.9 ± 0.2 vs.1.7 ± 0.3 μmol/kg, p=0.49; VL: 1.04 ± 0.2 vs. 1.03 ± 0.2 μmol/kg, p=0.97) or cGMP (sol: 4.8 ± 2.1 vs. 3.9 ± 1.5 vs. nmol/kg, p=0.22; VL 6.0 ± 3.8 vs. 5.8 ±3.2 nmol/kg, p=0.91). In a rat model of severe PH, acute BRJ dosing increases circulating and muscle NO₃⁻ but does not alter muscle blood flow. Absence of change in muscle NO₂⁻ and cGMP suggest insufficiently altered downstream NO signaling with BRJ supplementation.

Key Points: Body fluid volumes are significantly higher at the end of the 3-day interdialytic interval compared with the 2-day interdialytic interval. V_E/VCO₂ slope, a noninvasive index of exercise pulmonary vascular resistance, is elevated after the 3-day interdialytic interval. VO₂Peak is similar across interdialytic intervals but was limited following dialysis by postdialysis fatigue. Background: The long interdialytic interval in thrice-weekly hemodialysis is associated with volume accumulation and excess cardiovascular risk. Few studies have evaluated cardiovascular functional changes after interdialytic intervals. This study sought to evaluate cardiovascular functional response patterns, as assessed by cardiopulmonary exercise testing, after the short and long interdialytic intervals. Methods: We conducted an exploratory single-center, quasi-experimental 2-arm study involving crossover of treatment sequences in patients on conventional thrice-weekly maintenance hemodialysis. All patients underwent cardiopulmonary exercise testing, bioelectrical impedance spectroscopy, and physical function testing on three study visits: posthemodialysis and prehemodialysis at the end of a 2-day and the 3-day interdialytic intervals. Results: Thirty-one patients (n=19 men, mean [SD] age 55 [12] years, median [interquartile range] dialysis vintage 56 [24–96] months) completed all study visits. Interdialytic weight gain and total body fluid were greater after the 3-day compared with the 2-day interval (P < 0.001). Ventilation/carbon dioxide production (V_E/VCO₂) slope, a noninvasive index of exercise pulmonary vascular resistance and right ventricular (RV) dysfunction, was significantly elevated at the 3-day (31.2 [4.8] L V_E/L VCO₂; P = 0.002) compared with the 2-day interval (29.5 [3.9] L V_E/L VCO₂). No significant differences between interdialytic intervals were observed for peak oxygen uptake (VO₂Peak) or VO₂ at the anaerobic threshold. Change (Δ) in V_E/VCO₂ slope (ΔV_E/VCO₂) the 2-day to the 3-day interval was correlated with Δbody weight (r=0.36, P = 0.04) and left ventricular mass index (r=0.44, P = 0.02). Conclusions: The long interdialytic interval is associated with abnormal exercise-derived ventilatory and hemodynamic responses, including ventilation-perfusion mismatch and potentially RV dysfunction and RV-pulmonary artery uncoupling during exercise as suggested by elevated V_E/VCO₂ slope.

Introduction/Aims: Post activation potentiation (PAP) is an inherent characteristic of muscle wherein an increase in twitch force is observed after voluntary activation. This phenomenon is believed to be largely due to phosphorylation of the regulatory light chain of myosin. In rodents and other species, PAP occurs predominantly or exclusively in fast twitch muscles. However, it has been suggested that in humans PAP occurs more or less independently of muscle fiber type. Methods: 18 healthy men and women (27±8 y) underwent an electrical muscle stimulation protocol during which two sets of four twitches were elicited both pre and post 6 s maximal voluntary contractions of both the triceps surae (60-70% slow twitch) and triceps brachii (60-70% fast twitch) muscles. Results: Unpotentiated peak twitch torque (PTT) was higher in the larger triceps surae vs. the smaller triceps brachii (i.e., 13.4±5.3 vs. 3.4±2.1 Nm; P = 8.22 × 10 ⁻¹³ ), but time to peak torque was shorter (i.e., 84±7 vs. 132±14 ms; P = 6.92 × 10 ⁻¹⁴ ) and the relative rate of torque development (RTD) was greater in the triceps brachii (2294±257 vs. 1425±102 %/s; P = 1.93 × 10 ⁻¹¹ ). PAP increased PTT and the absolute RTD by 172±124% and 240±170% in triceps brachii versus only 20±20% and 31±24% in triceps surae, respectively (P = 1.26 × 10 ⁻⁴ and 1.30 × 10 ⁻⁴ , respectively). However, PAP-induced changes in half-relaxation time and the relative rate of relaxation did not differ between the two muscle groups. Discussion: We conclude that PAP influences contraction but not relaxation of human muscle in a fiber type dependent manner.

Antiseptic mouthwash use is widespread due to its oral health benefits. However, its impact on systemic physiological processes, particularly nitric oxide (NO) bioavailability and muscle contractility, is not fully understood. We sought to determine the effects of cetylpyridinium (antibacterial) versus sodium chloride (control) mouthwashes on salivary and breath NO markers and muscle contractile function in healthy young adults. Thirty participants (n = 15/group) completed a randomized, parallel-arm, blinded trial, comparing the two mouthwashes before and after 7 d of treatment. NO bioavailability was inferred via measurement of salivary nitrate (NO₃⁻), nitrite (NO₂⁻), and cyclic guanyl monophosphate (cGMP) concentrations and breath NO level. Contractile function of the knee extensor muscles was determined via isokinetic dynamometry. No changes in salivary NO₃⁻, NO₂⁻, or cGMP or in breath NO were observed in response to either treatment. However, cetylpyridinium mouthwash reduced the percentage of NO₂⁻ in saliva (17 ± 10% vs. 25 ± 13%; p = 0.0036). Peak torque at velocities of 0–6.28 rad/s was unaffected by mouthwash use. Calculated maximal knee extensor velocity (Vmax) and power (Pmax) were therefore also unchanged. Cetylpyridinium mouthwash reduces the relative abundance of NO₂⁻ in the oral cavity but does not significantly diminish overall NO bioavailability or impair muscle contractile function in healthy young adults.