Pflugers Archiv : European journal of physiology最新文献

Blood volume (BV) expansion by means of intravenous infusion of colloids is an established procedure in clinical interventions. The essential questions of how much of the infused fluid stays in the circulation according to measured changes in hemoconcentration are uncertain. A placebo-controlled, single-blinded, and cross-over design was implemented to assess the effect of a definite increment in BV on hemodilution, as determined by hemoglobin concentration ([Hb]). Healthy women (n = 17) and men (n = 19) matched by sex, age (age = 26 ± 4 vs. 27 ± 3 yr, P = 0.522), and physical activity were subjected in a blind manner to the intravenous infusion of placebo-sham (PBO-sham) via saline infusion (10 mL; BD 0.9% NaCl) or albumin (volume equivalent to 10% of BV; Albumin CSL 20%). [Hb] was slightly reduced (-2.4%) after the PBO-sham infusion. For the albumin infusion, the amount of fluid infused ranged from 325 to 810 mL (547 ± 112 mL) in order to elicit a 10% increment in BV in each individual. [Hb] was markedly reduced (-17.2%) (13.8 ± 1.6 vs. 11.5 ± 1.4 g·dL^-1, P < 0.001) after albumin infusion. The magnitude of hemodilution was well above the expected decrement (-9%) in all individuals. Sex differences were not detected. Cardiac chamber volumes were expanded by 7-10% by albumin infusion, without changes in LV filling pressure (P = 0.582). In conclusion, a colloid infusion eliciting a 10% BV expansion is markedly overestimated according to changes in [Hb] in healthy women and men. The overestimation of BV expansion ranges from 35 to 135% irrespective of sex.

Unlike secondary prevention, primary prevention of the major cardiovascular events has not yet been successful. One of the reasons is that current methodology has not succeeded in selecting high risk patients who are suitable candidates for primary prevention. Increased arterial stiffness, a known risk factor for cardiovascular events, has been commonly indexed by the pulse transit time (PTT), even though PTT is influenced by short-term blood pressure (BP) change. PTT and arterial BP of 93 human adults were analyzed. To determine the relationship between PTT and systolic blood pressure (SBP), the data was fitted to an exponential equation $(\mathrm{PTT}=\alpha {\times e}^{-\frac{\beta \times \mathrm{SBP}}{2}})$ which is derived from physiological theory. The index β in this equation, which reflects arterial stiffness, was found to be independent of SBP (R² = 0.006, p = 0.5088), while PTT had poor correlation with β (R² = 0.202, p < 0.0001). We propose a new index of arterial stiffness, $\frac{-2\times \frac{\Delta \mathrm{PTT}}{\Delta \mathrm{SBP}}}{\mathrm{PTTmean}}$ , which is independent of BP. This index is shown to approximate β and correlate well with it (R² = 0.935, p < 0.0001). PTT is affected by short-term BP changes, which makes it difficult to use for estimating arterial stiffness based on a single measurement in the hospital. Furthermore, it is difficult to estimate BP only from PTT, because BP itself is affected by arterial stiffness in addition to PTT. The proposed index characterizes the severity of atherosclerosis, independently of temporary BP change.

Chronic primary low back pain (cpLBP) is a leading contributor to years lived with disability. Early-life stress is a major risk factor predisposing to cpLBP later in life upon minor injuries. We investigated sex differences in the involvement of microglia in the pathophysiology of early-life stress effects on pain responses to a secondary stimulus in adulthood. During adolescence, male and female Wistar Han rats underwent repeated restraint stress for 12 consecutive days, while controls were handled. In adulthood, acute LBP was induced by NGF or saline injections into the lumbar multifidus muscle. Subsequently, the animals were sacrificed and perfused for spinal cord extraction. A total of 3516 microglia cells were classified into three functional states (surveillant, primed, activated) using partition around medoids clustering and UMAP dimensionality reduction methods for eight 3-dimensional morphological features obtained from MATLAB 3DMorph. Across all conditions, the proportion of surveillant microglia was significantly higher in females than in males (p < 0.0001, d = 1.85), while males had more primed (p < 0.0001, d = 1.56) and activated (p < 0.01, d = 1.87) microglia. Priming by stress led to an increase in activated microglia after NGF injection (p < 0.05, d = 0.63), more distinct in males (p < 0.05, d = 0.82) than in females (p > 0.05, d = 0.43). Additive effect of stress and NGF caused a shift towards primed state in males (p > 0.05, d = 0.62), but not in females. In conclusion, stress was confirmed to play a critical role in priming microglia and predisposing to cpLBP. Sex differences previously shown for neuropathic pain were found to be also relevant in this more frequent musculoskeletal pain condition.

The necessary energy supply in skeletal muscles is based on either glycolysis or mitochondrial oxidative phosphorylation (OxPhos). These two bioenergetic pathways are in balanced complementation. Glycolysis is faster than OxPhos, whereas OxPhos is much more efficient. One common feature of both pathways is the compartmentation of high-energy phosphates and their metabolic channeling. The glycolytic muscles are wider, whereas oxidative muscles have significantly more mitochondria. Importantly, a striking difference in bioenergetic mechanisms in oxidative (slow-twitch) versus glycolytic (fast-twitch) muscles and muscle fibers has been clearly shown. The advantage is that the optimal fiber diversity can provide the best muscle function. Various creatine kinase isoforms and phosphocreatine play an important role in glycolytic and oxidative muscles energy metabolism, but their roles are very different, depending on the muscle type. In the glycolytic muscles, phosphocreatine, produced from creatine and ATP by cytosolic creatine kinase, is mostly considered a cellular energy store for fast ATP delivery, whereas in the oxidative muscles, phosphocreatine and mitochondrial creatine kinase are the main players in the intracellular energy transport.

Increased weight-bearing load has previously been shown to reduce body weight in obese rodents, primarily by lowering food intake. However, it remains unclear whether increased loading also affects body weight through acute changes in extracellular water. This study aimed to determine whether increased weight-bearing load acutely produces negative sodium and water balances, as indicators of changes in whole-body extracellular sodium and water content. Diet-induced obese (DIO) rats were housed in metabolic cages with free access to hypotonic 0.5% NaCl solution and a low-sodium, high-fat diet. A novel, less traumatic loading method was used, where intra-abdominal capsules implanted two weeks earlier were either filled in vivo with wolfram granulate (Load group) or sham-filled (Control group), resulting in 15% and 2% increases in body weight, respectively. Compared to controls, increased weight-bearing load decreased body weight by 4.2% (95% CI -6.3, -2.0; P = 0.001) and reduced food intake by 1.6 percentage points (95% CI -2.6, -0.6; P = 0.003). No significant differences in sodium or water balance were observed. These findings suggest that load-induced reductions in body weight are not mediated by changes in whole-body extracellular sodium or water content, indicating that fluid homeostasis does not contribute to the homeostatic regulation of body weight.

Hypoxia has been extensively studied as a stressor which pushes human bodily systems to responses and adaptations. Nevertheless, a few evidence exist onto constituent trains of motor unit action potential, despite recent advancements which allow to decompose surface electromyographic signals. This study aimed to investigate motor unit properties from noninvasive approaches during maximal isometric exercise in normobaric hypoxia. Applying a cross-over design, 18 participants (gender-matched, on average age 22.6 y, BMI 23.6 kg/m², and bioimpedance phase angle 6.4) were exposed twice to hypoxia (FiO₂ ≊ 15.0% and FiO₂ ≊ 13.4%, separately, by using a tent connected with a hypoxic generator) and once to normobaric normoxia. After ≊ 30 min inside the tent, participants performed a series of 9 unilateral isometric contractions of the right knee extensors at maximum intensity for 5 s, interspersed with 15 s of passive recovery, while acquiring high-density surface EMG signals through a 64-electrodes grid and cardiorespiratory variables, and registering symptoms; then, a post-processing motor unit decomposition technique was applied. We found an increase in MU discharge rate as a response to acute normobaric hypoxia, although to a little extent and differently across sexes. Moreover, males experienced a more prominent increase of MU conduction velocity due to hypoxia. MUs responses to normobaric hypoxia were only slightly and non-homogeneously associated with hypoxic cardiorespiratory responses. Normobaric hypoxia affects the neuromuscular system with a relatively greater effect on peripheral rather than central features.

Myocardial performance index (MPI) has been used in the estimation of ventricular function in a non-invasive way through echocardiography. This index has presented relevant results in clinical and experimental studies. However, there are no studies evaluating whether this index correlates with other cardiac parameters in experimental models of heart disease, such as monocrotaline-induced pulmonary artery hypertension (PAH) and acute myocardial infarction (AMI). In view of that, the present study evaluated rats submitted to PAH and perform a broad analysis of echocardiographic, hemodynamic and morphometric parameters of the right ventricle (RV) and pulmonary artery (PA). Besides that, the present study also evaluated rats submitted to experimental AMI and performed a broad echocardiographic evaluation of left ventricle (LV). Subsequently, it was analyzed whether the parameters collected presented correlation with the MPI. In PAH model, monocrotaline was administrated and the animals were divided into the following groups: control and PAH. In AMI model, infarction was induced by coronary artery ligation and the groups were as follows: SHAM and AMI. In PAH model, MPI presented correlation with RV functional parameters, as well as with parameters that evaluate flow and resistance in the PA. In addition, this index also presented correlation with LV parameters in infarcted rats. To our knowledge, this is the first study that evaluates the correlation of MPI with parameters of the RV in rats with PAH induce by monocrotaline. Besides that, this is the first study that compares the use of this index in two different experimental models of cardiac diseases.

Sepsis enhances the anticontractile effect of perivascular adipose tissue (PVAT), which contributes to a reduced response to vasoconstrictor agents. In the early stages of sepsis, the renin-angiotensin-aldosterone system (RAAS) is activated, and this response can lead to poorer clinical outcomes. We hypothesized that AT₁ receptors (AT₁R) contribute to vascular hyporesponsiveness during sepsis by increasing the expression of inducible nitric oxide synthase (iNOS) in the periaortic PVAT, resulting in elevated nitric oxide (NO) production. In our study, male Wistar Hannover rats underwent lethal sepsis via a cecal ligation and puncture (CLP) model. We evaluated the role of AT₁R in sepsis-induced PVAT dysfunction by administering a single dose of losartan (a selective AT₁R antagonist; 10 mg/kg, gavage) to the rats 1 h prior to the CLP surgery. We observed increased levels of circulating angiotensin II in septic rats. Functional analyses revealed that AT₁R blockade prevented the enhanced anticontractile effect of PVAT and the resulting vascular hyporesponsiveness to phenylephrine during sepsis. Additionally, losartan inhibited sepsis-induced iNOS expression and the overproduction of NO in both the PVAT and the aorta. Experiments using 1400W, a selective iNOS inhibitor, indicated that iNOS plays a crucial role in the sepsis-induced increase in the anticontractile effect of PVAT. In summary, AT₁R mediate iNOS expression in PVAT, leading to the overproduction of NO, which ultimately contributes to sepsis-induced vasoplegia. Furthermore, AT₁R-mediated iNOS expression is an important mechanism related to vasoplegia in the vasculature. The present results implicate AT₁R as active players in sepsis-induced PVAT and vascular dysfunction.

In muscle fibers, unloading and disuse cause an increase in resting calcium concentrations in the cytosol and mitochondrial matrix. S107, a stabilizer of the Ryanodine Receptor calcium channel (RyR), blocks the leakage from the sarcoplasmic reticulum and lowers mitochondrial calcium concentrations without altering cytosolic calcium levels, as demonstrated in a recent article published in Pflugers Archives (Sidorenko et al. 2025). This finding is important as it shows that, even at rest, calcium entry into the mitochondria is influenced by RyR leakage, thanks to the mitochondria unique location near the sarcoplasmic reticulum membranes. Given the role of mitochondrial function in controlling muscle fiber size, these findings may have a significant translational relevance in the treatment of disuse-induced atrophy.

During periods of muscle disuse, calcium accumulates in the myoplasm of slow-tonic muscle fibers, leading to multiple negative consequences for muscle function. Leaky ryanodine receptors (RyRs) could contribute to this excessive accumulation of calcium. We hypothesized that the administration of S-107, a stabilizer of RyRs, would reduce the accumulation of calcium in the myoplasm/mitochondria and improve rat soleus muscle function during disuse. Male Wistar rats underwent 7 days of hindlimb suspension (HS), receiving S-107 in their food daily throughout the experiment. Seven days of HS led to cytosolic and mitochondrial calcium accumulation, enhanced mitochondrial respiration, and reduced mitochondrial biogenesis in the soleus muscle. This was accompanied by reductions in the proportion of slow-type myofibres, maximal isometric force, and fatigue resistance. Administering S-107 during HS prevented the accumulation of calcium in the mitochondria and the overactivation of mitochondrial respiration. It also attenuated the decline in markers of mitochondrial biogenesis and the decrease in fatigue resistance. S-107 treatment also partially prevented the decline in the soleus muscle force production but had only a minor effect on myoplasmic calcium accumulation. Our findings suggest that the destabilization of RyRs during muscle disuse leads to an accumulation of calcium in both the mitochondria and the myoplasm, which in turn causes a decline in muscle strength and resistance to fatigue.