Journal of applied physiology最新文献

Physiological-based cord clamping (PBCC) involves aeration of the newborn lung before umbilical cord clamping. As the infant can continue to receive oxygen from the mother during PBCC, the dynamics of transplacental oxygen transfer are unknown, particularly following the onset of pulmonary gas exchange. We have investigated the effects of pulmonary ventilation with supplemental oxygen during PBCC on transplacental oxygen transfer in preterm lambs. Pregnant ewes and their fetuses (n = 8; 127 days of gestation; term 147 days) were instrumented with catheters and flow probes under general anesthesia to measure oxygen transfer across the placenta. Before umbilical cord clamping, lambs were intubated and mechanically ventilated with a fraction of inspired oxygen ([Formula: see text]) that increased every 10 min, from 0.21 to 0.5 and then 1.0. Data were analyzed using a mixed-effects analysis with a Holm-Šídák post hoc test. During PBCC, ventilation of lambs significantly decreased oxygen uptake across the placenta from 317.7 ± 15.0 to 166.5 ± 26.9 (P = 0.0028) and to 73.6 ± 34.3 mL/min/kg (P = 0.0009) at [Formula: see text] levels of 0.21 and 0.5, respectively. Ventilation with a [Formula: see text] of 1.0 reversed oxygen uptake across the placenta (-37.2 ± 14.0 mL/min/kg; P < 0.0001), resulting in oxygen transfer from lamb to ewe. In contrast, oxygen delivery to the lamb, via the umbilical vein, remained unchanged with increasing [Formula: see text] (P = 0.4485). During PBCC, pulmonary oxygen uptake by the newborn reduces oxygen uptake across the placenta, and when oxygen levels are in excess, the mother acts as an "oxygen sink," reducing the risk of hyperoxemia of the newborn.NEW & NOTEWORTHY This study investigated transplacental oxygen transfer during physiological-based cord clamping in preterm lambs. During physiological-based cord clamping, ventilating newborn lambs reduced oxygen uptake across the placenta and that ventilation with high oxygen (1.0 [Formula: see text]) reversed the oxygen gradient, resulting in newborn to mother oxygen transfer. Our findings indicate that the mother can act as an "oxygen sink" that protects the newborn from excess oxygen during physiological-based cord clamping.

Pregnancy at advanced maternal age (AMA, ≥35 yr) is increasingly common in developed countries. Delayed pregnancy may elevate the risk of adverse pregnancy outcomes, such as hypertensive disorders, potentially due to altered arterial structure and function or insufficient vascular adaptations during pregnancy. Therefore, this study aimed to characterize differences in maternal vascular and autonomic function across pregnancy and postpartum in healthy pregnant women of AMA compared with younger pregnant women by retrospectively analyzing data from 57 younger pregnant women (21-30 yr; 27 ± 3 yr) and 22 pregnant women of AMA (≥35 yr; 36 ± 1 yr). Arterial stiffness, remodeling, and endothelial function were assessed using carotid-femoral and carotid-brachial pulse wave velocity (cfPWV and cbPWV), carotid β-stiffness, carotid intima-media thickness (IMT), and brachial artery flow-mediated dilation (FMD) in the first, second, and third trimesters and postpartum (4-14 wk). Beat-to-beat blood pressure variability (BPV), cardiovagal baroreflex sensitivity (BRS), and heart rate variability (HRV) were also assessed. The AMA group exhibited higher cfPWV, cbPWV, β-stiffness, and IMT compared with the younger group during pregnancy (P ≤ 0.03), with cfPWV and cbPWV remaining higher in the postpartum period (P ≤ 0.01). The AMA group also had higher systolic BPV, lower BRS, and lower HRV compared with the younger group during pregnancy (P ≤ 0.04), with consistently lower BRS postpartum (P < 0.01). Blood pressure and FMD did not differ between groups throughout pregnancy and postpartum (P ≥ 0.27). These findings suggest that women of AMA have higher central arterial stiffness and altered autonomic function throughout pregnancy, which may contribute in part to increased risk of pregnancy complications.NEW & NOTEWORTHY This study assessed the impact of advanced maternal age (AMA) on vascular and autonomic function across all three trimesters. Compared with younger pregnant women, women of AMA exhibited higher arterial stiffness and greater carotid intima-media thickness, and impaired autonomic regulation throughout pregnancy, despite no significant difference in endothelial function. These observed differences may represent early subclinical changes in AMA women, which may bring them closer to a physiological threshold where complications may occur.

We investigated the effects of high altitude (HA) on postactivation potentiation (PAP) of the quadriceps muscles in 18 healthy adults (10 females). At sea level (SL; 300 m), and again after 1-2 and 11-13 days of residing at 3,800 m (HA1 and HA2, respectively), single electrical stimuli were delivered to the femoral nerve to quantify parameters of the resting twitch and the maximal compound muscle action potential (M_max), before and 2-300 s after a 10-s maximal voluntary contraction (i.e., the conditioning contraction). PAP was quantified by comparing peak force of twitches evoked after the conditioning contraction to the control twitch before it. On all days of testing, twitches were potentiated from 2 to 180 s (P ≤ 0.003). At SL, PAP was greater for males than females 2 and 15 s after the conditioning contraction (by 29.6% and 17.5%, respectively; P ≤ 0.005). For males, PAP was ∼19% lower at HA1 than SL (P ≤ 0.001), a deficit that persisted at HA2 (P = 0.001). Conversely, the magnitude of PAP did not change with HA for females (P ≥ 0.808). Finally, the M_max amplitude was greater at HA1 and HA2 compared with SL (P ≤ 0.039), with no difference between the sexes. From our findings, it can be suggested that mechanisms related to PAP of the quadriceps muscles are affected by HA (3,800 m) in healthy adult males but not females.NEW & NOTEWORTHY The capacity of the quadriceps muscles to become potentiated following a 10-s isometric maximal voluntary contraction became attenuated for males following 1-2 days of residing at 3,800 m above sea level and did not recover by 11-13 days. Conversely, for females, the magnitude of postactivation potentiation was unaffected by high altitude. Peak-to-peak amplitude of the maximal compound muscle action potential was augmented by high altitude for both males and females.

Phrenic long-term facilitation (pLTF) is a form of respiratory motor plasticity, expressed as a lasting increase in phrenic nerve activity following acute intermittent hypoxia (AIH). Whereas AIH also elicits ventilatory LTF (vLTF) in unanesthetized rats, concurrent hypercapnia (elevated background or episodic hypercapnia) is required for vLTF in humans. One major difference between rodent and human studies is the diurnal phase (nocturnal rats vs. diurnal humans). Diurnal phase regulates pLTF magnitude and mechanism; 15, 1-min hypoxic episodes elicit more robust pLTF in the rest (∼130%) versus active phase (∼30%) in rats. Thus, we assessed differences in pLTF elicited by acute intermittent hypercapnic-hypoxia (AIHH) versus AIH in mid-rest versus mid-active phase rats. In anesthetized, paralyzed, vagotomized, and ventilated male Sprague-Dawley rats (n = 7 per group), pLTF was assessed following moderate AIH (arterial Po₂ range 35-49 mmHg; 15, 1-min episodes) or AIHH (arterial Pco₂ range 46-50 mmHg) in the mid-rest (noon) and mid-active phases (midnight). In contrast to expectations, mid-rest phase pLTF 90-min post-AIHH (64 ± 45%) was less than that elicited by AIH (132 ± 93%; P < 0.001). As reported previously, AIH-induced pLTF was lower in mid-active (46 ± 47%; P = 0.050) versus mid-rest rats; however, AIHH-induced pLTF was not significantly different in mid-rest versus mid-active phase rats (37 ± 28%; P = 0.20), and there was no longer a significant difference between AIH versus AIHH in the active phase (P = 0.650). Thus, adding hypercapnia to an AIH protocol suppresses pLTF in anesthetized rats exclusively in the mid-rest, but not mid-active phase of the diurnal cycle. Possible mechanisms for hypercapnia and time-of-day effects are discussed.NEW & NOTEWORTHY Diurnal variations in acute intermittent hypoxia (AIH)-induced respiratory plasticity were evident in young, male rats, with robust phrenic long-term facilitation (pLTF) during their mid-rest phase and reduced pLTF during the mid-active phase. Surprisingly, adding hypercapnia (AIHH) suppressed pLTF during the mid-rest phase, with minimal impact during the mid-active phase. These results contrast with diurnal humans, where hypercapnia is necessary for ventilatory LTF, revealing species and time-of-day-dependent mechanisms that shape AIH efficacy.

Limb-lengthening procedures are predicated on bone health, with little consideration for soft tissues. For instance, a distraction rate of 1 mm/day is conventionally prescribed to patients based on bone remodeling, with little regard for muscles. Nonhuman animal studies suggest that the use of slower than conventional distraction rates mitigate muscle damage and the decline in joint function, but such human data are elusive. Because muscle mechanics largely govern overall joint mechanics, we compared the knee function (range of motion and strength) of patients who underwent femoral lengthening at conventional versus slower distraction rates (Avg ± SD; 0.91 ± 0.13 or 0.54 ± 0.15 mm/day, respectively) to implicate underlying muscle function. Both groups were of similar age (d = 0.10, P = 0.425) and underwent similar lengthening magnitudes (d = 0.12, P = 0.671). At terminal distraction phase, the slower distraction rate group exhibited a 56% greater recovery in knee range of motion (d = 1.25, P = 0.008) and a 44% greater knee extensor strength versus convention (d = 1.02, P = 0.046). At the same mutual day after surgery, despite not achieving statistical significance, the slower versus conventional distraction rate group exhibited a 39% greater recovery in knee range of motion (d = 0.48, P = 0.180) and similar knee extensor strength (d = 0.11, P = 0.430). Despite our meager sample size, using a slower than conventional distraction rate in limb-lengthening patients elicited superior joint function at terminal distraction and numerically better joint function at ∼3 mo after surgery. Therefore, considering muscle health, in addition to bone health, when devising limb-lengthening procedures may expedite patient recovery.NEW & NOTEWORTHY Limb-lengthening procedures are predicated on bone health, with little consideration for muscle health. Here, we show that using slower than conventional limb-lengthening rates, which better accommodate muscle remodeling, expedites the recovery of patient joint function.

When individuals present with hand injuries, clinicians often use the contralateral hand as an internal control. However, subtle differences in baseline dexterous abilities between the dominant and nondominant hands are poorly understood. To address this gap, here we quantified such differences, measured as independence (individuation) and smoothness of finger movements. A cohort of 47 right-hand-dominant healthy adults (22 males and 25 females) moved each finger independently 10 times, while joint angle data were tracked with a dataglove (CyberGlove III, CyberGlove Systems, San Jose, CA). Each finger's performance was compared with its counterpart on the opposite hand using Wilcoxon-signed rank tests. The right hand scored significantly higher than the left on both direct comparison and linear mixed-effect modeling for thumb individuation (P < 0.0001) and smoothness (P < 0.0001), index finger individuation (P = 0.012), and middle finger individuation (P = 0.009). Differences between the hands for index and middle finger individuation scores changed depending on the individuation scoring method used. Sex-based comparisons revealed females had greater asymmetry of thumb (P = 0.044) and ring finger (P = 0.020) individuation scores, as well as ring finger smoothness (P = 0.036) compared with males on both direct comparison and multiple linear regression. Cluster and principal components analysis were performed to detect whole hand differences. Dominant and nondominant hands were separated using smoothness metrics at a 74.5% sensitivity, 66% specificity, 68.6% positive predictive value, and 72.1% negative predictive value. In sum, this represents the largest study to date quantifying naturally occurring differences in hand dexterity between dominant and nondominant hands in healthy, right-handed young adults.NEW & NOTEWORTHY Here we present the largest study to date quantifying differences in finger dexterity between the dominant and nondominant hands in healthy, right-hand-dominant, young adults using finger individuation and smoothness. To our knowledge, we are the first to demonstrate differences between dominant and nondominant thumb, index, and middle finger dexterity metrics. Whole hand analyses indicate the dominant and nondominant hands can be separated based on smoothness with above-chance sensitivity and specificity.

The purpose of the study was to determine how sex, anthropometry, and chronic resistance training affect neuromuscular measures of the biceps brachii. Fifteen male resistance-trained (RT), 15 male nonresistance-trained (non-RT), 10 females RT, and 10 females non-RT individuals (n = 50) participated in this study. First, participants' anthropometry measurements were recorded. Second, participants performed isometric maximum voluntary contractions (MVCs) of the dominant elbow flexors and the interpolated twitch technique. Then, participants received transcranial magnetic stimulation (TMS) to determine resting and active motor threshold (during 10% MVC) to elicit a motor evoked potential (MEP) and Erb's point stimulation to determine maximal compound action potential (M_max) of the biceps brachii. Finally, participants performed 14, 5-s isometric contractions at 10% MVC and received TMS or an Erb's point stimulation. Males had greater muscle thickness (64%) but lower body fat percentage (24%) compared with females. RT participants exhibited significantly greater muscle thickness (28%), MEP (81%), and M_max amplitudes (79%), and shorter half relaxation time (19%) and MEP latency (9%) compared with non-RT participants (all P < 0.05). The MEP/M_max ratio did not differ between any of the groups. RT was the strongest positive predictor of both MEP and M_max amplitudes, whereas higher fat indices were negatively associated. Muscle thickness increased MEP only in trained individuals, with the association being stronger in males than in females. This study highlights training and sex-specific differences when assessing various central and peripheral neuromuscular measures that are due, in part, to morphological and physiological variances.NEW & NOTEWORTHY Here we show that training and sex alter central and peripheral neuromuscular output measures due to morphological and physiological differences and adaptations. These differences should be taken into consideration when designing studies to determine mechanisms underlying changes in neuromuscular output, especially when considering corticospinal excitability and whether or not it is normalized between and within participants.

Caffeine is a well-known stimulant that is widely used to increase alertness and performance. However, there is little information on the effect of chronic caffeine consumption on exercise adaptations. We first sought to characterize the effect of caffeine on protein synthesis in vitro using immortalized C2C12 and TTD6 muscle and tendon cells. Total protein synthesis, as measured by puromycin incorporation, decreased 31% in TTD6 cells with 4 mM caffeine (P < 0.05) and 41% in C2C12 cells with 0.5 mM caffeine (P < 0.01). The structure and function of in vitro engineered ligaments were also reduced with caffeine, including a 45% reduction in maximal tensile load (P = 0.0128) and 30% reduction in collagen content (P = 0.0038) with 1 mM caffeine. To assess the effect of caffeine in vivo, sedentary and running mice were provided with a moderately high dose of caffeine (0.22 mg/mL, roughly equivalent to 5.7 mg/kg for a human) or water as a placebo control. Free access to a running wheel was effective in increasing gastrocnemius, soleus, and heart muscle mass relative to body weight, oxidative phosphorylation proteins, and Achilles tendon collagen concentration and Col1a1 gene expression. Mice that consumed caffeine while exercising did not gain skeletal muscle mass (gastrocnemius and soleus) to the same extent as the noncaffeinated exercising mice. Together, these data suggest that high caffeine consumption can dampen the molecular signals associated with protein synthesis and in excess may limit exercise-induced skeletal muscle adaptations.NEW & NOTEWORTHY It is possible for high doses of caffeine to dampen the adaptive response to exercise. In cell culture, muscle and tendon cells have lower protein synthesis with caffeine. Caffeine also reduced the mechanical properties of engineered ligaments. In mice, muscle mass gains with 6 wk of exercise are limited with a high physiological dose of caffeine (roughly equivalent to a human dose of 5.7 mg/kg).

Endothelium-derived hyperpolarizing factors (EDHFs), produced via cytochrome P-450 2C9 (CYP2C9) pathways, influence vascular function; however, their contribution to flow-mediated dilation (FMD) remains unclear. Thirty participants (15 males, 15 females; 22 ± 3 yr) underwent two randomized, double-blinded, counterbalanced sessions ≥72 h apart. Two hours before testing, they ingested either 150 mg fluconazole (FLZ, CYP2C9 inhibitor) or a placebo (PLA). FMD was assessed using duplex ultrasound following a 5-min proximal upper arm occlusion. FLZ did not alter baseline diameter, peak diameter, or total shear rate (P > 0.05). Conversely, FLZ reduced absolute (Δmm: PLA: 0.36 ± 0.10 vs. FLZ: 0.31 ± 0.11, P = 0.03, [Formula: see text]= 0.15) and relative FMD (Δ%: PLA: 10.09 ± 3.44 vs. FLZ: 8.91 ± 3.82, P = 0.05, [Formula: see text]= 0.13). Interestingly, FLZ attenuated absolute (Δmm: PLA: 0.35 ± 0.09 vs. FLZ: 0.27 ± 0.09, P = 0.03, d: 0.52) and relative FMD (Δ%: PLA: 8.41 ± 2.06 vs. FLZ: 6.77 ± 2.59, P = 0.05, d: 0.46) in males, whereas no differences were observed in females (Δmm: PLA: 0.36 ± 0.11, FLZ: 0.34 ± 0.11, P = 0.18, d = 0.25; Δ%: PLA: 11.76 ± 3.77, FLZ: 11.04 ± 3.70, P = 0.16, d = 0.26). Allometric scaling for relative FMD preserved the FLZ effect and male-specific attenuation and eliminated sex differences. Therefore, CYP2C9 pathways contribute to FMD in young adults, with a more pronounced effect in males, suggesting that males rely more on P450-mediated mechanisms for endothelium-dependent vasodilation.NEW & NOTEWORTHY This study demonstrates that inhibiting CYP2C9 significantly reduces brachial artery flow-mediated dilation (FMD) in young, healthy adults, implicating CYP2C9-derived metabolites as a mediator of endothelium-dependent vasodilation. Notably, CYP2C9 inhibition attenuated FMD in males, whereas females maintained their vasodilatory response, suggesting sex-specific reliance on CYP2C9 signaling. These findings enhance our understanding of sex differences in vascular regulation and may inform future strategies for preserving endothelial health.