Physiological Reports最新文献

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.

Cardiac autonomic functioning is altered in children and young adults born preterm with very low birth weight (VLBW; <1500 g). Whether these alterations persist into mid-adulthood remains unknown. We studied heart rate variability (HRV) in two birth cohorts, HeSVA (Finland) and NTNU LBW Life (Norway), with harmonized methods. HRV was assessed in 107 adults born preterm with VLBW and 142 controls born term with normal birth weight at a mean age of 36 (SD 3.3) years. We hypothesized that adults born preterm with VLBW have lower parasympathetic activity and higher blood pressure (BP), partly mediated by lower parasympathetic activity. Participants born preterm with VLBW had higher heart rate and BP than controls. In sex-stratified analyses, mean differences in high-frequency (HF) power were -43.3% (95% CI -63.9%, -11.3%) in women and -36.9% (-65.0%, 15.0%) in men. For root mean square of successive differences, differences were -18.2% (-35.6%, 4.1%) in women and 18.5% (-10.4%, 58.4%) in men. Low-frequency (LF) power differed by -23.7% (-46.2%, 10.5%) in women and 35.0% (-16.5%, 120.3%) in men. LF/HF ratio was 36.3% (4.1%, 76.8%) higher in women and -13.9% (-34.3%, 12.7%) in men. Among women, elevated BP was partly mediated by HRV. Findings suggest altered autonomic regulation in adults born preterm with VLBW, especially women, potentially contributing to higher BP.

The effects of TRPC6 activation for various periods of time on three classes of functional outputs were examined in cultured podocytes: albumin permeation across a confluent layer; changes in nephrin dynamics; and cell death. Albumin permeation in transwell assays was significantly increased within 1 h in response to the activation of formyl peptide receptors (FPR), but the TRPC6 inhibitor SAR-7334 had no effect on this response, and 1 h or 24 h exposures to the TRPC6 activator PPZ2 did not increase albumin permeation. Direct TRPC6 activation for 24 h evoked an increase in shedding of nephrin ectodomains into the surrounding media, accompanied by an increase in matrix metalloprotease-7 (MMP-7). These effects were blocked by the calcineurin inhibitor cyclosporin A (CsA), as well as by Batimastat, a broad-spectrum inhibitor of metalloproteinases including MMP-7. TRPC6 activation for 24 h also evoked an increase in occludin abundance but had no effect on the abundance of podocin. Finally, TRPC6 activation for 72 h, but not for 24 h, evoked an increase in apoptotic cell death based on increases in cleaved caspase-3. This effect was blocked by both SAR-7334 and CsA. TRPC6 activation did not induce pyroptosis based on the measurement of cleaved gasdermin D.

Menopause leads to loss of cardiovascular and renal protection, and while hormone therapy offers benefits, its efficacy may depend on health status at menopause onset. We hypothesized that preexisting hypertension blunts the renal, cardiac, and vascular effects of Estradiol (E2). Female Long-Evans rats were ovariectomized (OVX) at 46 weeks to model menopause and received either E2 or vehicle, and some were infused with angiotensin II (ANG; 700 ng/kg/min) 4 weeks before OVX. Blood pressure (BP) was measured by tail cuff, renal function by urine collection, collagen deposition by histology, and mRNA expression in aorta and kidney by droplet digital PCR. ANG increased BP and proteinuria (p = 0.02), water intake (p < 0.001), urinary output, heart weight, and aortic NOX4 (p < 0.01), confirming hypertension and oxidative stress. E2 reduced body weight (p = 0.02), increased bone mineral content (p = 0.01), and prevented uterine atrophy (p < 0.001), confirming E2 treatment. While E2 attenuated cardiac hypertrophy (p = 0.004), it exacerbated proteinuria, decreased GFR (p < 0.05), and failed to reduce aortic NOX4. ANG did not affect tissue estrogen receptor expression, while E2 showed tissue-specific regulation of GPER and ERα. In this hypertensive OVX model, E2 failed to protect renal and vascular damage, emphasizing the importance of cardiovascular health at menopause when considering hormone therapy.

Melorheostosis is a rare sclerosing bone dysplasia that can clinically and radiologically mimic common bone disorders, particularly in atypical presentations. Its heterogeneous manifestations and limited awareness among clinicians frequently contribute to diagnostic delays or misdiagnosis. We report the case of a 34-year-old woman with chronic forearm pain and a longstanding subcutaneous mass. She was initially misdiagnosed as having a metabolic bone disorder based on imaging and histopathology. However, subsequent evaluation with MRI and bone scintigraphy demonstrated eccentric cortical thickening and longitudinal sclerotic lesions involving the radius, olecranon, and first metacarpal. Normal biochemical markers and the absence of systemic involvement further supported a diagnosis of melorheostosis. Histopathological re-examination confirmed lamellar cortical bone with osteoblastic rimming but remained nonspecific. This case underscores the importance of considering melorheostosis in the differential diagnosis of sclerosing bone disorders, especially when radiographic features are ambiguous. It highlights the critical role of multimodal imaging in establishing an accurate diagnosis, while histopathology provides complementary but not definitive evidence. Importantly, melorheostosis may also serve as a window into bone physiology, illustrating aberrant osteogenesis and dysregulated cortical remodeling. A better understanding of its molecular basis, particularly MAPK pathway alterations, may ultimately facilitate more targeted and effective treatments.

Changes to the extracellular matrix support acute wound healing following myocardial infarction. Fibroblasts regulate the composition of the extracellular matrix, in part, by secreting hyaluronan. Details surrounding the regulation, source, and impact of hyaluronan production after MI are largely unknown. We recently showed that activated fibroblasts produce hyaluronan via Has2; however, the extent to which this function impacts acute ventricular remodeling following myocardial infarction (MI) has not been tested. Hence, the goal of the present study was to elucidate the impact of fibroblast-borne Has2 expression in acute ventricular remodeling. Adult, male and female mice were subjected to non-reperfused myocardial infarction and followed for 1 week and subjected to echocardiography and hearts were harvested for pathology and biochemical analyses. Mice were deficient in fibroblast-derived Has2 (Has2^-/-) or were littermate controls that were sufficient in fibroblast Has2. At 1-week post-MI, Has2^-/- male mice had exacerbated heart failure reflected by lower cardiac output due to lower stroke volume, when compared to littermate males. The genotype effect was not evident in female mice. To assess potential mechanisms, we examined hearts for fibrosis, cardiomyocyte cross-sectional area, and capillary density; there were no significant differences in any of these endpoints. Deletion of Has2 also did not impact collagen organization, which could have indicated changes in ventricular stiffness. Fibroblast-derived Has2 supports cardiac function early after MI. The mechanism responsible for this and why it is not evident in female mice is unclear.