Frontiers in Physiology

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EISSN: 1664042X
Published by: Frontiers Media SA
Total articles ≅ 15,095

Latest articles in this journal

Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1024238

Abstract:
Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique provided pre-conditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate the ability to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries known to induce acute kidney injury (AKI). The rate of transgene expression was approximately 33% and 30% in rats with prerenal AKI that received treatments 1 (T1hr) and 24 (T24hr) hours after the injury was established, respectively. The resulting mitochondrial adaptation via exogenous IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) significantly blunted the effects of injury within 24 h of administration: decreased serum creatinine (≈60%, p < 0.05 at T1hr; ≈50%, p < 0.05 at T24hr) and blood urea nitrogen (≈50%, p < 0.05 at T1hr; ≈35%, p < 0.05 at T24hr) levels, and increased urine output (≈40%, p < 0.05 at T1hr; ≈26%, p < 0.05 at T24hr) and mitochondrial membrane potential, Δψm, (≈ by a factor of 13, p < 0.001 at T1hr; ≈ by a factor of 11, p < 0.001 at T24hr), despite elevated histology injury score (26%, p < 0.05 at T1hr; 47%, p < 0.05 at T24hr). Therefore, this study identifies an approach that can boost recovery and halt the progression of AKI at its inception.
Kajal Kamra, Nikolay Karpuk, Irving H. Zucker, Harold D. Schultz,
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1101408

Abstract:
Introduction: Acute lung injury (ALI) initiates an inflammatory cascade that impairs gas exchange, induces hypoxemia, and causes an increase in respiratory rate (fR). This stimulates the carotid body (CB) chemoreflex, a fundamental protective reflex that maintains oxygen homeostasis. Our previous study indicated that the chemoreflex is sensitized during the recovery from ALI. The superior cervical ganglion (SCG) is known to innervate the CB, and its electrical stimulation has been shown to significantly sensitize the chemoreflex in hypertensive and normotensive rats. We hypothesized that the SCG is involved in the chemoreflex sensitization post-ALI.Methods: We performed a bilateral SCG ganglionectomy (SCGx) or sham-SCGx (Sx) in male Sprague Dawley rats 2 weeks before inducing ALI (Week −2 i.e., W-2). ALI was induced using a single intra-tracheal instillation of bleomycin (bleo) (day 1). Resting-fR, Vt (Tidal Volume), and V̇ E (Minute Ventilation) were measured. The chemoreflex response to hypoxia (10% O2, 0% CO2) and normoxic-hypercapnia (21% O2, 5% CO2) were measured before surgery on W (−3), before bleo administration on W0 and on W4 post-bleo using whole-body plethysmography (WBP).Results: SCGx did not affect resting fR, Vt and V̇E as well as the chemoreflex responses to hypoxia and normoxic hypercapnia in either group prior to bleo. There was no significant difference in ALI-induced increase in resting fR between Sx and SCGx rats at W1 post-bleo. At W4 post-bleo, there were no significant differences in resting fR, Vt, and V̇E between Sx and SCGx rats. Consistent with our previous study, we observed a sensitized chemoreflex (delta fR) in response to hypoxia and normoxic hypercapnia in Sx rats at W4 post-bleo. However, at the same time, compared to Sx rats, the chemoreflex sensitivity was significantly less in SCGx rats in response to either hypoxia or normoxic hypercapnia.Discussion: These data suggest that SCG is involved in the chemoreflex sensitization during ALI recovery. Further understanding of the underlying mechanism will provide important information for the long-term goal of developing novel targeted therapeutic approaches to pulmonary diseases to improve clinical outcomes.
Pablo Sánchez-Aguilera, Camila López-Crisosto, Ignacio Norambuena-Soto, Christian Penannen, Jumo Zhu, Nils Bomer, Matijn F. Hoes, Peter Van Der Meer, Mario Chiong, , et al.
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1106662

Abstract:
A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.
Valeria Páez, Maria Rodriguez-Fernandez, Juan Silva-Urra, Cristian Núñez-Espinosa,
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1110477

Abstract:
Background: Athletes, tourists, and mining workers from all over the world ascend daily to an altitude greater than 3.000 meters above sea level to perform different activities, all of which demand physical effort. A ventilation increase is the first mechanism once the chemoreceptors perceive hypoxia, and is key to maintaining blood oxygen levels during acute exposure to high altitudes and to buffering lactic acidosis during exercise. It has been observed that gender is a variable that can influence the ventilatory response. Still, the available literature is limited due to the few studies considering women as study subjects. The influence of gender on anaerobic performance and its effects under high altitudes (HA) environments have been poorly studied.Objective: The objectives of this study were to evaluate anaerobic performance in young women exposed to high altitudes and to compare the physiological response to multiple sprints between women and men measured by ergospirometry.Methodology: Nine women and nine men (22.9 ± 3.2 years old) carried out the multiple-sprint anaerobic tests under two conditions, sea level and high altitudes.Results: In the first 24 h of exposure to a high altitudes, lactate levels were higher in women than those in men (2.57 ± 0.4 Mmol/L, 2.18 ± 0.3 Mmol/L, respectively; p < 0.05). Second, women had a decreased ventilatory response in exposure to high altitudes compared to men (p > 0.005). Third, there is a positive correlation between lactate levels prior to an anaerobic test and the ventilatory response developed by subjects at high altitudes (R2 = 0.33, slope = -41.7, and p < 0.05). Lastly, this ventilatory response can influence VO2peak (R2 = 0.60, slope = 0.02, and p < 0.001).Conclusion: This study provides insights into the mechanisms behind the reduced respiratory capacity observed in women during an anaerobic exercise test at high altitudes. An acute response to HA showed a greater work of breathing and increased the drive ventilatory response. It is possible to postulate the differences in the fatigue-induced metaboreflex of the respiratory muscles and aerobic–anaerobic transition between genders. These results on multiple sprint performance and the influences of gender in hypoxic environments deserve further investigation.
Liam Hovey, Xiaoyun Guo, Yi Chen, Qinghang Liu, William A. Catterall
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1049611

Abstract:
The cardiac calcium channel CaV1.2 conducts L-type calcium currents that initiate excitation-contraction coupling and serves as a crucial mediator of β-adrenergic regulation of the heart. We evaluated the inotropic response of mice with mutations in C-terminal phosphoregulatory sites under physiological levels of β-adrenergic stimulation in vivo, and we assessed the impact of combining mutations of C-terminal phosphoregulatory sites with chronic pressure-overload stress. Mice with Ser1700Ala (S1700A), Ser1700Ala/Thr1704Ala (STAA), and Ser1928Ala (S1928A) mutations had impaired baseline regulation of ventricular contractility and exhibited decreased inotropic response to low doses of β-adrenergic agonist. In contrast, treatment with supraphysiogical doses of agonist revealed substantial inotropic reserve that compensated for these deficits. Hypertrophy and heart failure in response to transverse aortic constriction (TAC) were exacerbated in S1700A, STAA, and S1928A mice whose β-adrenergic regulation of CaV1.2 channels was blunted. These findings further elucidate the role of phosphorylation of CaV1.2 at regulatory sites in the C-terminal domain for maintaining normal cardiac homeostasis, responding to physiological levels of β-adrenergic stimulation in the fight-or-flight response, and adapting to pressure-overload stress.
Pietro Ciliberti, Danilo Cardim, Alberto Giardina, Matjaž Groznik, Lorenzo Ball, Martina Giovannini, Denise Battaglini, Erta Beqiri, Basil Matta, Peter Smielewski, et al.
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1113386

Abstract:
Introduction: Potential detrimental effects of hyperoxemia on outcomes have been reported in critically ill patients. Little evidence exists on the effects of hyperoxygenation and hyperoxemia on cerebral physiology. The primary aim of this study is to assess the effect of hyperoxygenation and hyperoxemia on cerebral autoregulation in acute brain injured patients. We further evaluated potential links between hyperoxemia, cerebral oxygenation and intracranial pressure (ICP).Methods: This is a single center, observational, prospective study. Acute brain injured patients [traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH)] undergoing multimodal brain monitoring through a software platform (ICM+) were included. Multimodal monitoring consisted of invasive ICP, arterial blood pressure (ABP) and near infrared spectrometry (NIRS). Derived parameters of ICP and ABP monitoring included the pressure reactivity index (PRx) to assess cerebral autoregulation. ICP, PRx, and NIRS-derived parameters (cerebral regional saturation of oxygen, changes in concentration of regional oxy- and deoxy-hemoglobin), were evaluated at baseline and after 10 min of hyperoxygenation with a fraction of inspired oxygen (FiO2) of 100% using repeated measures t-test or paired Wilcoxon signed-rank test. Continuous variables are reported as median (interquartile range).Results: Twenty-five patients were included. The median age was 64.7 years (45.9–73.2), and 60% were male. Thirteen patients (52%) were admitted for TBI, 7 (28%) for SAH, and 5 (20%) patients for ICH. The median value of systemic oxygenation (partial pressure of oxygen-PaO2) significantly increased after FiO2 test, from 97 (90–101) mm Hg to 197 (189–202) mm Hg, p < 0.0001. After FiO2 test, no changes were observed in PRx values (from 0.21 (0.10–0.43) to 0.22 (0.15–0.36), p = 0.68), nor in ICP values (from 13.42 (9.12–17.34) mm Hg to 13.34 (8.85–17.56) mm Hg, p = 0.90). All NIRS-derived parameters reacted positively to hyperoxygenation as expected. Changes in systemic oxygenation and the arterial component of cerebral oxygenation were significantly correlated (respectively ΔPaO2 and ΔO2Hbi; r = 0.49 (95% CI = 0.17–0.80).Conclusion: Short-term hyperoxygenation does not seem to critically affect cerebral autoregulation.
Yali Tian, Hanif Ullah, Jun Gu, Ka Li
Published: 8 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1123692

Abstract:
The interaction of post-traumatic stress disorder (PTSD) and atherosclerosis (AS) increase the risk of mortality. Metabolism and immunity play important roles in the comorbidity associated with PTSD and AS. The adenosine monophosphate-activated protein kinase/mammalian target of rapamycin and phosphatidylinositol 3-kinase/Akt pathways are attractive research topics in the fields of metabolism, immunity, and autophagy. They may be effective intervention targets in the prevention and treatment of PTSD comorbidity with AS. Herein, we comprehensively review metabolic factors, including glutamate and lipid alterations, in PTSD comorbidity with AS and discuss the possible implications in the pathophysiology of the diseases.
Timothy Warwick, Giulia Karolin Buchmann, Beatrice Pflüger-Müller, Manuela Spaeth, Christoph Schürmann, Wesley Abplanalp, Lukas Tombor, David John, Andreas Weigert, Martin Leo-Hansmann, et al.
Published: 7 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1125864

Abstract:
Treatment of vascular stenosis with angioplasty results in acute vascular damage, which may lead to restenosis. Owing to the highly complex cellularity of blood vessels, the healing response following this damage is incompletely understood. To gain further insight into this process, scRNA-seq of mouse carotid tissue after wire injury was performed. Stages of acute inflammation, resolution and remodeling were recapitulated in these data. To identify cell types which give rise to neointima, analyses focused on smooth muscle cell and fibroblast populations, and included data integration with scRNA-seq data from myocardial infarction and atherosclerosis datasets. Following carotid injury, a subpopulation of smooth muscle cells which also arises during atherosclerosis and myocardial infarction was identified. So-called stem cell/endothelial cell/monocyte (SEM) cells are candidates for repopulating injured vessels, and were amongst the most proliferative cell clusters following wire-injury of the carotid artery. Importantly, SEM cells exhibit specific transcriptional profiles which could be therapeutically targeted. SEM cell gene expression patterns could also be detected in bulk RNA-sequencing of neointimal tissue isolated from injured carotid vessels by laser capture microdissection. These data indicate that phenotypic plasticity of smooth muscle cells is highly important to the progression of lumen loss following acute carotid injury. Interference with SEM cell formation could be an innovative approach to combat development of restenosis.
, Philippe Kersten, Roel M. Maas, Ep H. Eding, Mike S. M. Jetten, Henk Siepel, Sebastian Lücker, , Maartje A. H. J. Van Kessel
Published: 7 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1111404

Abstract:
Ammonia accumulation is a major challenge in intensive aquaculture, where fish are fed protein-rich diets in large rations, resulting in increased ammonia production when amino acids are metabolized as energy source. Ammonia is primarily excreted via the gills, which have been found to harbor nitrogen-cycle bacteria that convert ammonia into dinitrogen gas (N2) and therefore present a potential in situ detoxifying mechanism. Here, we determined the impact of feeding strategies (demand-feeding and batch-feeding) with two dietary protein levels on growth, nitrogen excretion, and nitrogen metabolism in common carp (Cyprinus carpio, L.) in a 3-week feeding experiment. Demand-fed fish exhibited significantly higher growth rates, though with lower feed efficiency. When corrected for feed intake, nitrogen excretion was not impacted by feeding strategy or dietary protein, but demand-fed fish had significantly more nitrogen unaccounted for in the nitrogen balance and less retained nitrogen. N2 production of individual fish was measured in all experimental groups, and production rates were in the same order of magnitude as the amount of nitrogen unaccounted for, thus potentially explaining the missing nitrogen in the balance. N2 production by carp was also observed when groups of fish were kept in metabolic chambers. Demand feeding furthermore caused a significant increase in hepatic glutamate dehydrogenase activities, indicating elevated ammonia production. However, branchial ammonia transporter expression levels in these animals were stable or decreased. Together, our results suggest that feeding strategy impacts fish growth and nitrogen metabolism, and that conversion of ammonia to N2 by nitrogen cycle bacteria in the gills may explain the unaccounted nitrogen in the balance.
Micaela Sinclair-Black, R. Alejandra Garcia,
Published: 7 February 2023
Frontiers in Physiology, Volume 14; https://doi.org/10.3389/fphys.2023.1112499

Abstract:
Commercial laying hens can produce one egg approximately every 24 h. During this process, regulatory systems that control vitamin D3 metabolism, calcium and phosphorus homeostasis, and intestinal uptake of these minerals work in concert to deliver components required for eggshell calcification and bone mineralization. Commercial production cycles have been extended in recent years to last through 100 weeks of age, and older hens often exhibit an increased prevalence of skeletal fractures and poor eggshell quality. Issues such as these arise, in part, through imbalances that occur in calcium and phosphorus utilization as hens age. As a result, an in-depth understanding of the mechanisms that drive calcium and phosphorus uptake and utilization is required to develop solutions to these welfare and economic challenges. This paper reviews factors that influence calcium and phosphorus homeostasis in laying hens, including eggshell formation and development and roles of cortical and medullary bone. Metabolism and actions of vitamin D3 and physiological regulation of calcium and phosphorus homeostasis in key tissues are also discussed. Areas that require further research in avian species, such as the role of fibroblast growth factor 23 in these processes and the metabolism and action of bioactive vitamin D3, are highlighted and the importance of using emerging technologies and establishing in vitro systems to perform functional and mechanistic studies is emphasized.
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