Physiological Reports最新文献

Exercise prescription for Duchenne muscular dystrophy (DMD) is complicated by the susceptibility of unstable skeletal muscle to contraction-induced damage. Although evidence suggests that isometric contractions can confer molecular and physiological benefits to DMD muscle, their impact on viscoelastic properties has not been assessed in vivo. Given that DMD is characterized by muscular instability due to the absence of dystrophin, we employed "myomechanical profiling"-a custom apparatus compatible with an MCR702e rheometer-to evaluate stiffness, compressibility, and elasticity of the tibialis anterior muscle of male mice following a bout of submaximal isometric fatiguing exercise. Fatigue was standardized to a 50% reduction in strength. Immediately after exercise, both dystrophin-positive (wildtype) and dystrophin-deficient (mdx) muscles exhibited reduced compressibility. Storage and loss moduli, reflecting stiffness and energy dissipation during rotational deformation, increased markedly in fatigued wildtype muscle but remained unchanged in mdx muscle. Conversely, elasticity was unaffected in wildtype muscle but shifted mdx muscle toward a more viscous state. These findings indicate that compressibility, stiffness, and energy storage capacity are not disproportionately affected in dystrophin-deficient muscle compared to wildtype muscle following fatiguing contractions. Thus, metabolically fatiguing, non-lengthening contractions appear not to compromise viscoelastic properties in dystrophin-deficient muscle, supporting their potential clinical use without exacerbating muscle instability.

The heart constantly adapts to acute hemodynamic load by increasing contractility and stretch-induced compliance (SIC). The latter involves titin phosphorylation, notably by cGMP-dependent protein kinase (PKG). Given that Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) also phosphorylates titin and is activated under acute stress via redox signaling, we hypothesized a role for CaMKII in SIC. We assessed passive tension (PT) decay in the 15 min following sudden stretch in isometrically contracting rabbit right ventricular papillary muscles, with or without PKG or CaMKII inhibition. Additionally, Wistar Han rat hearts were Langendorff-perfused and acutely stretched or left unstretched. Skinned cardiomyocytes extracted from these hearts were analyzed for sarcomere length-PT relationships before and after incubation with PKG, CaMKII, or both. Both kinases reduced PT, with diminished effects in pre-stretched cells, suggesting prior kinase activation. PKG inhibition significantly blunted SIC, while CaMKII inhibition showed a similar but non-significant trend. Our findings support that CaMKII contributes to SIC, likely via shared phosphorylation targets with PKG. These results provide mechanistic insight into SIC and suggest CaMKII as a potential modulator of diastolic function during acute stretch, such as in preload challenges.

This study aimed to assess the cutaneous analgesic effect of the lidocaine-synephrine combination and its underlying α-adrenergic receptor-mediated mechanism in comparison with phenylephrine. Cutaneous analgesia after subcutaneous drug injection was assessed by inhibition of the cutaneous trunci muscle reflex in response to needle pinpricks on the shaved dorsal skin of Sprague-Dawley rats. Synephrine, like the local anesthetic lidocaine, is capable of inducing cutaneous analgesia but is less potent. On an equipotent basis (ED₂₅, ED₅₀ [50% effective dose], and ED₇₅), the block duration induced by synephrine or phenylephrine was longer than that induced by lidocaine (p < 0.01). When combined with lidocaine, the ED₅₀ for synephrine decreased from 326 (183-579) μmol/kg to 141 (128-156) μmol/kg (p < 0.01), and for phenylephrine, it decreased from 15.8 (9.0-27.9) μmol/kg to 6.2 (5.9-6.6) μmol/kg (p < 0.01). Lidocaine (ED₉₅) in combination with either synephrine (52 μmol/kg) or phenylephrine (1.6 μmol/kg) prolonged the duration of action (p < 0.001), while phentolamine (0.3 μmol/kg) reversed these effects. We concluded that synephrine produces dose-dependent cutaneous analgesia that is less potent but longer-lasting than lidocaine. The enhanced analgesic effects of the lidocaine-synephrine and lidocaine-phenylephrine combinations are mediated through α-adrenergic receptor activation.

Pupillometry has long been proposed as a noninvasive physiological measure for emotional valence. However, its empirical effectiveness remains inconclusive due to confounding visual and emotional factors. This study examined whether pupil response patterns alone can reliably distinguish between positive and negative emotional stimuli while explicitly controlling for visual complexity (spatial frequency; SF) and emotional arousal at three standardized levels. Fifty images (25 positive and 25 negative) were presented, and pupil responses were recorded. Dynamic time warping-based clustering captured temporal variations and similarities in pupil size responses across visual conditions. Initial classification without controlling SF and arousal yielded near-chance accuracy (~57%) despite luminance control. However, performance improved substantially when stimuli were segmented by specific arousal-SF combinations. Under a representative low arousal, high spatial-frequency condition (SF level 4), the best-performing configuration (logistic regression) achieved a mean classification accuracy of approximately 79% and an AUC of 0.88, with consistently high precision, recall, and specificity across cross-validation folds. Feature importance analyses highlighted critical pupillary parameters, including the area under the pupil dilation curve, as key predictors. These results suggest that pupillary responses can reliably indicate emotional valence under rigorously controlled visual conditions, emphasizing control of perceptual and emotional factors in pupillometry-based emotion research.

While conventional tobacco-cigarette smoking continues to decline, e-cigarette (E-cig) use is rising, yet its physiological consequences remain poorly characterized. Chronic activation of the aryl hydrocarbon receptor (AHR) by tobacco smoke impairs skeletal muscle mitochondrial function. Here, we evaluated whether E-cig vapor elicits AHR activation and mitochondrial dysfunction in skeletal muscle. C2C12 mouse myoblasts were exposed to 1% dimethyl sulfoxide (vehicle), 0.02% tobacco-smoke condensate (TSC), or vape condensate (VC) at 0.006%, 0.06%, and 0.3%. Cell viability, AHR-pathway gene expression (Ahr, Ahrr, Cyp1a1), and mitochondrial respiration were assessed. Male C57BL/6J mice (12-16 weeks; n = 4-5/group) underwent acute 2-h or 4-week exposure to room air, tobacco smoke, or E-cig vapor. Serum cotinine, gastrocnemius AHR-pathway genes, muscle contractility, and mitochondrial function were evaluated. In myoblasts, 0.02% TSC and 0.3% VC upregulated Ahrr and Cyp1a1 (p < 0.0001) and reduced complex I state-3 respiration (p < 0.05) without affecting viability. In mice, acute exposure to tobacco smoke and E-cig vapor significantly increased serum cotinine (p < 0.0001), but only tobacco-smoke activated AHR-pathway. Chronic exposure to tobacco smoke and E-cig vapor reduced mitochondrial complex I and II state-3 respiration (p < 0.05), without altering muscle contractile function. These findings suggest that AHR-independent mechanisms contribute to mitochondrial dysfunction with E-cig vapor exposure.

This case study investigated the psychophysiological stress responses of a diver during and after a 24-h hyperbaric exposure. Comprehensive biomarker analysis revealed relevant changes in oxidative stress parameters and cardiac muscle markers. Notably, a critical time point at 6 h (T2) emerged, characterized by peak oxidative stress and diminished antioxidant capacity, followed by progressive cardiac strain as evidenced by elevated creatine kinase isoenzime (CK-MBm) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. Despite these physiological challenges, no pathological tissue damage was detected, indicating effective endogenous defense mechanisms. Moreover, no significant psychophysiological symptoms were detected before, during, and after the dive, except for tiredness and insomnia. Cognitive assessments reflected adaptive shifts in response strategies under prolonged stress, emphasizing the importance of monitoring to prevent operational risks. These findings highlight the need to consider dive duration carefully, suggesting that introducing rest intervals or personnel rotation around the critical T2 threshold may mitigate physiological fatigue and optimize performance. This study provides valuable insights into human adaptation to extended hyperbaric conditions and informs safety protocols for commercial and military diving operations.

Exercise promotes myocardial angiogenesis, yet molecular responses vary by modality, and cardiac-specific evidence in healthy models remains fragmented. This study aimed to map biomolecular regulators of myocardial/coronary angiogenesis across exercise types in healthy animal models. PRISMA-ScR scoping review. Literature searches were conducted in PubMed, Scopus, and SpringerLink. Eligible studies were structured exercise interventions in physiologically healthy animals reporting myocardial/coronary tissue angiogenesis biomarkers and/or structural microvascular indices; disease models and studies reporting only circulating markers were excluded. FITT parameters and outcomes were charted and synthesized by exercise type. From 4674 records, 23 studies were included across swimming, continuous treadmill/running, interval/HIIT, resistance, and combined training. Aerobic protocols most consistently upregulated the VEGF-VEGFR axis with downstream PI3K/Akt-eNOS/NO and context-dependent HIF-1α signaling. Interval/HIIT showed prominent endothelial activation (e.g., miR-126 and CD34/KDR) alongside increased vascular indices. Resistance/combined training was less represented, but implicated AMPK-PGC-1α/FNDC5-irisin signaling, VEGFR2/FLK-1 upregulation, and eNOS/NO support in combined protocols. Exercise modality appears to recruit distinct upstream regulators that converge on myocardial angiogenic remodeling; evidence is dominated by male-only models, and mechanistic data for resistance/combined training remain limited.

Breath-holding (BH), including variations of the Valsalva maneuver, is used during resistance exercise to stabilize the trunk and increase intra-abdominal pressure. However, its hemodynamic and ventilatory effects during low-to-moderate intensity strength training in women remain unclear. In a randomized crossover design, 17 healthy, young females performed squats at three intensities (bodyweight, 25%, and 50% of 10-repetition maximum) under two breathing conditions: BH or controlled breathing (CB) during the concentric phase. Cardiopulmonary responses were assessed using impedance cardiography, spirometry, and auscultatory arterial blood pressure measurement. Across intensities, BH elicited significantly higher heart rate (+2%-5%; p < 0.01), cardiac output (+3%-8%; p = 0.02), systolic blood pressure (+16%-23%; p < 0.01), rate-pressure product (+20%-30%; p < 0.01), and rating of perceived exertion (+14%-19%; p < 0.01) than CB. Oxygen uptake (-11%-15%; p < 0.01) and minute ventilation (-16%-17%; p < 0.01) were significantly reduced during BH, followed by a post-exercise overshoot. Stroke volume and blood lactate did not differ significantly. Even at low-to-moderate intensities, BH during resistance exercise induces moderate cardiovascular strain and transient ventilation reductions. In healthy, young women, these responses remained within a non-critical range, suggesting that short, controlled BH may represent a viable and safe strategy during strength training.