Physiological Reports最新文献

Dispersion of repolarization results from a non-homogeneous recovery of excitability in cardiac tissue, and it is an important factor in arrhythmogenesis because it could lead to the initiation and maintenance of a variety of arrhythmias. Antiarrhythmic agents that prolong action potential duration (APD) by selectively blocking specific ion channels (like I_Kr) often increase dispersion of repolarization, which could result in a pro-arrhythmic risk. In this report, using computer models of the action potential of human epicardial, mid-myocardial, and endocardial myocytes, we have identified strategies to prolong APD without increasing transmural dispersion of repolarization. The first strategy, which involves blocking several depolarizing and repolarizing ion channels (I_NaL, I_CaL, I_Kr, and I_NaCa), can prolong APD while decreasing transmural APD dispersion by about 20%-60%, depending on the model. The second strategy, which involves the use of a combination of ion channel blockers and activators, can prolong APD while decreasing transmural APD dispersion by about 70%, a stronger reduction in transmural dispersion of repolarization than using only ion channel blockers. Our results suggest that a multichannel pharmacology strategy (as opposed to a single channel strategy), possibly using ion channel blockers and activators, can be effective at increasing APD while minimizing dispersion of repolarization.

Expression of concern: X.-J. Du, X.-H. Feng, Z.-Q. Ming, and H. Kiriazis, "Cardiomyopathy Characterizing and Heart Failure Risk Predicting by Echocardiography and Pathoanatomy in Aged Male Mice," Physiological Reports 12, no. 20 (2024): e70061. https://doi.org/10.14814/phy2.70061. This Expression of Concern is for the above article, published online on October 16, 2024 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Josephine C. Adams; The American Physiological Society; The Physiological Society; and Wiley Periodicals LLC. The Expression of Concern has been agreed upon after it was determined that the TG panel in figure 3a is duplicated from an article published in another journal 14 years earlier by an author common to both publications. The authors cooperated with the investigation and explained that the duplication was an inadvertent error; they also provided supporting data. However, although the conclusions are believed to remain unaffected, the journal has decided to issue an Expression of Concern to inform and alert readers of the duplication.

The popularity of ultra-endurance events and plant-based diets highlights the importance of understanding the energetics of athletes with diverse dietary preferences. This study examined energy balance in two recreational cyclists on plant-based diets (male, 41 years; female, 38 years) during a 30-day cross-Canada ride. Resting energy expenditure was measured via whole-room indirect calorimetry before and after the ride. Total energy expenditure (TEE) was assessed using doubly labeled water during the first and last weeks of the ride and used to calculate physical activity energy expenditure (PAEE) and physical activity level (PAL). Body composition was assessed with deuterium dilution, and dietary intake was recorded using food scales, written records, and photographs. Cyclists averaged 154.8 ± 24.0 km/day early and 118.2 ± 25.3 km/day late in the ride. Body weight showed minimal variation, but the male's fat mass decreased by 2.3 kg and fat-free mass increased by 1.4 kg. Both cyclists increased energy intake (female: +421 kcal/day; male: +761 kcal/day), with protein intake >2.3 g/kg/day. TEE increased in the female (+683 kcal/day) but remained relatively stable in the male (-137 kcal/day), driven by PAEE. PAL remained high (female: 3.71-4.11; male: 3.76-3.94). These findings highlight the high energy demands of ultra-endurance cycling and the need for tailored strategies, particularly for athletes on plant-based diets.

Aminoacyl-tRNA Synthetases (aaRS) are important regulators of cytokine signaling. Multiple cytoplasmic aaRS family members have been observed to be secreted in response to various stimuli to modulate downstream responses, however, agonist-induced cellular release of aaRS from mitochondria has not been described. In particular, TNFα is a potent mediator of aaRS release. BEAS-2B cells were utilized to study the release of mitochondrial Aspartyl-tRNA Synthetase (DARS2) in response to various cytokines. The role of DARS2 in paracrine signaling was evaluated using adoptive media transfer from BEAS-2B to recipient THP1 cells. To identify pathways governing DARS2 secretion, blocking antibodies chemical inhibitors and siRNA technology was employed. Herein, we describe DARS2 as the first mitochondrial aaRS released in response to TNFα from airway epithelia. Once secreted, DARS2 binds to macrophages, is internalized, thereby inducing an M1-like phenotype in recipient macrophages. DARS2 release from airway epithelia is in part, TNFα-receptor 1 dependent, and requires the endosomal sorting complex required for extracellular transport.

Food intake not only provides pleasure through exteroceptive sensations such as taste and smell but also elicits beneficial physiological effects via interoceptive signals arising from the gastrointestinal tract and beyond. Among these interoceptive pathways, vagal sensory (vagal afferent) nerves play a central role in transmitting food-derived information to the brain. This review first outlines the anatomical and functional characteristics of vagal sensory nerves. It then examines how food-related signals, including mechanical stretching of the gastrointestinal wall, gastrointestinal and pancreatic hormones such as glucagon-like peptide-1, and microbial metabolites like short-chain fatty acids, are detected by vagal pathways. These inputs collectively regulate food intake, nutrient preferences, and systemic metabolism. Recent studies further suggest that vagal sensory nerves enable the brain to anticipate and adapt to the metabolic demands of food intake, serving as a key mechanism for maintaining homeostasis during rapid postprandial changes. Understanding the role of vagal afferents in sensing meal-derived signals and mediating gut-brain communication provides insights into how interoceptive pathways orchestrate energy balance and hold promise for developing therapeutic strategies for metabolic disorders such as obesity and diabetes.

We investigated whether heat adaptation (HA) could be maintained in trained females following an initial acclimation period. The experimental group (EXP, n = 11) completed 10 sessions of HA over 2 weeks, followed by nine sessions of HA maintenance (HA_M) over 3 weeks. HA was induced with home-based stationary cycling while overdressing. A control group (CON, n = 4) was exposed to heart rate-matched thermoneutral training. Prior to and at the end of the acclimation period (PRE, MID) and following the maintenance period (POST), $\dot{V}{O}_2\max$ , peak power output (PPO), and hemoglobin mass (Hb_mass) were determined in 18°C, before a 20 km time trial (TT) in 35°C, 45% RH. During the TT, rectal and mean skin temperature (T_re, $\overline{T}$ _sk), heart rate, peak cardiac output ( $\dot{Q}\text{peak}$ ), and sweat rate were measured. PPO increased (p = 0.0003) and TT times decreased (p < 0.0001) from PRE to MID and POST in EXP but not CON. $\dot{V}{O}_2\max$ , T_re, $\overline{T}$ _sk, heart rate, and $\dot{Q}\text{peak}$ remained stable in both groups. Sweat rate only increased in EXP from PRE to POST (p = 0.0197). Hb_mass did not change in EXP. HA_M potentiated hot exercise performance compared to HA, as demonstrated by improvements in both temperate and hot conditions. While HA_M suffices to further develop thermal resistance, it is unsuitable to increase Hb_mass following 10 days of HA or 3 weeks of HA_M. Our findings demonstrate that females can achieve HA by overdressing at home for 10 days and that HA_M provides further benefits.

Firefighting increases afterload, leading to ventricular-arterial coupling mismatch in young firefighters that may contribute to coronary hypoperfusion and the elevated risk of on-duty cardiac events. Since this risk is higher with aging in firefighters, we examined their ventricular-vascular coupling and afterload responses to acute firefighting. Twenty-two male firefighters (40-59 years) performed 18-min high-intensity firefighting drills while wearing protective gear and breathing apparatus. Echocardiography was conducted before and within 10 min after firefighting to estimate cardiac volumes, while tonometry-derived pulse wave analysis estimated wasted pressure effort (Ew) and aortic reservoir function. Ventricular-arterial coupling was quantified using the arterial (Ea) to ventricular (Ees) elastance ratio, and coronary perfusion was estimated via the Buckberg index. Firefighting reduced stroke volume (difference (∆) = -17 mL, p < 0.001), Ew (∆ = -800 dyne cm^-2 s, p = 0.005), aortic reservoir function (∆ = -6.9%, p < 0.001), and Buckberg index (∆ = -0.28, p < 0.001). Firefighting augmented Ea/Ees (∆ = 0.10, p = 0.035) stemming from increases in Ea (∆ = 0.16 mmHg.mL^-1, p = 0.046) not counteracted by Ees. Heart rate changes were associated with Ew (r = -0.60, p = 0.017) and aortic reservoir function (r = -0.80, p < 0.001). Although middle-aged firefighters exhibited typical post-firefighting cardiovascular strain, including reduced coronary perfusion, the role of ventricular-arterial interactions and pulsatile afterload remains unclear due to heart rate confounding.

The functions of Growth Differentiation Factor 15 (GDF15) include actions on metabolism, cell survival, immune response, inflammation, and inhibition of food intake. Temporal variations in circulating GDF15 over 24 h have been reported in two small cohorts: one during fasted conditions and one during an overfeeding regimen. Here, 22 healthy young men were studied over 24 h in a controlled setting approximating normal daily life with blood sampling every third hour. Plasma GDF15 concentrations were analyzed using cosinor rhythmometry and one-way repeated measures ANOVA. In the full cohort, cosinor analysis did not show a statistically significant 24-h rhythm of GDF15 (p = 0.0944), but the ANOVA revealed a significant modest effect of time on plasma GDF15 concentrations (p < 0.001). Exploratory post hoc cosinor analysis of a subgroup of 14 subjects with evening-peaking profiles indicated modest rhythmic fluctuations (p = 0.0467), but the effect was small compared with the fluctuations of other metabolic hormones and plasma changes in GDF15 due to, for example, cancer and pregnancy. These findings do not provide definitive evidence for a 24-h rhythm of GDF15, but post hoc results suggest that some individuals may exhibit modest 24-h fluctuations. Larger, prospectively powered studies are required to confirm these observations and clarify their clinical significance.

When pain is associated with traumatic hemorrhage, medics must be concerned about secondary effects of analgesics on cardiorespiratory systems. A novel analog of acetaminophen, D-112, was developed to circumvent liver toxicity and improve analgesic efficacy. D-112 causes dose-related inhibition of formalin-induced licking. The objective of this study was to test the effects of D-112 on survival and cardiorespiratory variables following hemorrhage and extremity trauma (ET). We hypothesized that D-112 would significantly change cardiorespiratory responses to HEM and thereby decrease survival. Male rats received either vehicle (lactated Ringer's) or D-112 (50 mg/kg) after conscious hemorrhage of either 37% (n = 10, vehicle and D-112) or 50% (n = 8, vehicle; n = 11, D-112) of blood volume following ET, which consisted of soft tissue injury and fibula fracture. Rats were observed for 4 h after the start of hemorrhage. Neither survival times (37% hemorrhage: p = 0.474; 50% hemorrhage: p = 0.306) nor survival curves (37% hemorrhage: p = 0.146; 50% hemorrhage: p = 0.280) differed between treatments. Mean arterial pressure did not differ between treatments (37% hemorrhage: p = 0.742; 50% hemorrhage: p = 0.521). D-112 transiently elevated minute ventilation (p < 0.001) after both hemorrhages. D-112 does not alter cardiorespiratory responses to the point of depressing survival, suggesting that D-112 could be an appropriate analgesic following traumatic hemorrhage.

Chronic heart failure (CHF) is characterized by reduced peak oxygen consumption (VO_2peak). Cachexia may exacerbate the decline in VO_2peak from reductions in muscle mass and strength. We sought to assess differences in VO_2peak between patients with CHF and cachexia and those without. A systematic literature search of cohort studies via databases (PubMed, Web of Science, Scopus, and Cochrane Library) was conducted from inception until April 2025. A meta-analysis using a random-effects model was employed. Overall, 10 articles were included in this study. There was a statistically significant reduction of mean VO_2peak in patients with CHF and cachexia versus those without cachexia (k = 10; MD: -2.21 mL/kg/min, 95%confidence interval [CI]: -2.95 to -1.47, I² = 51%, p < 0.01). When cachexia was defined as weight loss of ≥7.5% over the last 6 months, results remained identical (k = 6; MD: -2.47, 95% CI: -2.92 to -2.01, I² = 11%, p < 0.01). Meta-regression analyses regarding age, sex, body mass index, and left ventricular ejection fraction showed no impact as potential moderators, and no publication bias was detected (p > 0.05). CHF patients with cachexia exhibit significantly decreased VO_2peak compared to their free-cachexia counterparts.