Dataset Information

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

ABSTRACT: Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ?30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

SUBMITTER: Zuo L

PROVIDER: S-EPMC4192541 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Zuo Li L Diaz Philip T PT Chien Michael T MT Roberts William J WJ Kishek Juliana J Best Thomas M TM Wagner Peter D PD

PloS one 20141009 10

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor m ...[more]

PMID: 25299212

Similar Datasets

Project description:BackgroundGout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain.MethodsMonosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca2+ imaging and behavioral assays were applied.ResultsModel mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA's inhibitory effect on NLRP3 inflammasome and further reversed EA's anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca2+ imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout.ConclusionsOur results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.

Project description:Although mechanical ventilation is a life-saving intervention in patients suffering from respiratory failure, prolonged mechanical ventilation is often associated with numerous complications including problematic weaning. In contracting skeletal muscle, inadequate oxygen supply can limit oxidative phosphorylation resulting in muscular fatigue. However, whether prolonged mechanical ventilation results in decreased diaphragmatic blood flow and induces an oxygen supply-demand imbalance in the diaphragm remains unknown.We tested the hypothesis that prolonged controlled mechanical ventilation results in a time-dependent reduction in rat diaphragmatic blood flow and microvascular PO2 and that prolonged mechanical ventilation would diminish the diaphragm's ability to increase blood flow in response to muscular contractions.Compared to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation resulted in a 75% reduction in diaphragm blood flow (via radiolabeled microspheres), which did not occur in the intercostal muscle or high-oxidative hindlimb muscle (e.g., soleus). There was also a time-dependent decline in diaphragm microvascular PO2 (via phosphorescence quenching). Further, contrary to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation significantly compromised the diaphragm's ability to increase blood flow during electrically-induced contractions, which resulted in a ~80% reduction in diaphragm oxygen uptake. In contrast, 6 hrs of spontaneous breathing in anesthetized animals did not alter diaphragm blood flow or the ability to augment flow during electrically-induced contractions.These new and important findings reveal that prolonged mechanical ventilation results in a time-dependent decrease in the ability of the diaphragm to augment blood flow to match oxygen demand in response to contractile activity and could be a key contributing factor to difficult weaning. Although additional experiments are required to confirm, it is tempting to speculate that this ventilator-induced decline in diaphragmatic oxygenation could promote a hypoxia-induced generation of reactive oxygen species in diaphragm muscle fibers and contribute to ventilator-induced diaphragmatic atrophy and contractile dysfunction.

Project description:Background: Electrocardiogram (ECG) contamination is present in diaphragm electromyography (EMGdi) recordings. Obtaining EMGdi without ECG contamination is crucial for EMG amplitude analysis. Manually selecting EMGdi in between QRS complexes has been most commonly applied in recent years (manual method). We developed a semi-automated analysis method based on Least Mean Square Adaptive Filtering combined with a synchronously recorded separate ECG channel to remove ECG artifacts from the EMGdi signals. We hypothesized that this approach would shorten analysis duration and might minimize the potential for inter-rater disagreement. Aims: We aimed to evaluate agreement between the semi-automated method and the manual method and inter-rater reliability of the manual method. Methods: Electromyography signals of seven patients with COPD were recorded using an esophageal catheter during an exercise test on a cycle ergometer. Four patients subsequently participated in an inspiratory muscle training (IMT) program for 8 weeks. After IMT, the tests were repeated. EMGdi/EMGdiMax as obtained either manually by the two assessors or retrieved from the semi-automated method were compared. Results: Semi-automated EMGdi/EMGdiMax agreed well with values obtained by one of the two manual assessors (assessor 1) both at pre-intervention measurements (mean difference -0.5%, 95% CI: -19.6 to 18.6%) and for the pre/post IMT differences (mean difference 1.2%, 95% CI: -16.8 to 19.2%). Intra-class correlation coefficients between methods were 0.96 (95% CI: 0.94-0.97) at pre-intervention measurements and 0.78 (95% CI: 0.58-0.89) for pre/post IMT differences (both p < 0.001). EMGdi/EMGdiMax from assessor 2 was systematically lower than from assessor 1 and agreed less well with the semi-automated method both at pre-intervention measurements (mean difference: 9.3%, 95% CI: -11.4 to 29.9%) and for pre/post IMT differences (mean difference 7.0%, 95% CI: -20.4 to 34.4%). Analysis duration of the semi-automated method was significantly shorter (29 ± 9 min) than the manual method (82 ± 20 min, p < 0.001). Conclusion: The developed semi-automated method is more time efficient and will be less prone to inter-rater variability that was observed when applying the manual analysis method. It is, therefore, proposed as a new standard for objective EMGdi amplitude analyses in future studies.

Dataset Information

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Publications

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets