Reply: Matching Minute Ventilation in the Hypermetabolic State of Dinitrophenol Poisoning.
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ABSTRACT:
SUBMITTER: McGillis ES
PROVIDER: S-EPMC7640730 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Reply: Matching Minute Ventilation in the Hypermetabolic State of Dinitrophenol Poisoning.
McGillis Eric S ES Olives Travis D TD Cole Jon B JB
Annals of the American Thoracic Society 20201101 11
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Project description: Not available
| S-EPMC7640731 | biostudies-literature
Project description:ObjectiveExposure to organophosphates (OP) may lead to a life threatening cholinergic crisis with death attributed to a rapidly progressive respiratory failure. In a toxicological mass casualty event involving organophosphate exposure, many of the victims may depend on immediate short-term ventilation to overcome the respiratory distress which may exhaust life supporting resources. In addition, the mandatory use of personal protective gear by first responders emphasizes the need for a noninvasive, easy-to-operate ventilation device. Our objective was to assess the efficacy of MRTX, a Biphasic Cuirass Ventilation device, in comparison with standard bag-valve mask ventilation following acute organophosphate poisoning.MethodsPigs were exposed to paraoxon poisoning (1.4 LD50), and treated 8 min later with atropine (0.05 mg/kg). The control group received no further support (n = 9), the two experimental groups received ventilation support initiated 15 min post exposure and lasted for 25 min: one group was ventilated with the commonly used bag-valve mask (Mask group, n = 7) and the other was ventilated with the Biphasic Cuirass Ventilation device (Cuirass group, n = 7). Clinical signs and physiological parameters were monitored during the first hour, and mortality up to 24 h post exposure was recorded.ResultsNo mortality was observed in the Cuirass group following OP poisoning, while mortality in the Control and in the Mask groups was high (67% and 71%, respectively). Mouth excretions of the cuirass-ventilated animals were frothy white as in deep suctioning, as opposed to the clear saliva-like appearance of secretions in the other two groups. No further group differences were recorded.ConclusionsThe noninvasive, easy-to-operate Biphasic Cuirass Ventilation device was effective in reducing OP-induced mortality and might be advantageous in an organophosphate mass casualty event. This finding should be validated in further investigations.
| S-EPMC5598215 | biostudies-literature
Project description:Crosstalk between cellular metabolism and circadian rhythms is a fundamental building block of multicellular life, and disruption of this reciprocal communication could be relevant to degenerative disease, including cancer. Here, we investigated whether maintenance of circadian rhythms depends upon specific metabolic pathways, particularly in the context of cancer. We found that in adult mouse fibroblasts, ATP levels were a major contributor to overall levels of a clock gene luciferase reporter, although not necessarily to the strength of circadian cycling. In contrast, we identified significant metabolic control of circadian function in an in vitro mouse model of pancreatic adenocarcinoma. Metabolic profiling of a library of congenic tumor cell clones revealed significant differences in levels of lactate, pyruvate, ATP, and other crucial metabolites that we used to identify candidate clones with which to generate circadian reporter lines. Despite the shared genetic background of the clones, we observed diverse circadian profiles among these lines that varied with their metabolic phenotype: the most hypometabolic line had the strongest circadian rhythms while the most hypermetabolic line had the weakest rhythms. Treatment of these tumor cell lines with bezafibrate, a peroxisome proliferator-activated receptor (PPAR) agonist shown to increase OxPhos, decreased the amplitude of circadian oscillation in a subset of tumor cell lines. Strikingly, treatment with the Complex I antagonist rotenone enhanced circadian rhythms only in the tumor cell line in which glycolysis was also low, thereby establishing a hypometabolic state. We further analyzed metabolic and circadian phenotypes across a panel of human patient-derived melanoma cell lines and observed a significant negative association between metabolic activity and circadian cycling strength. Together, these findings suggest that metabolic heterogeneity in cancer directly contributes to circadian function, and that high levels of glycolysis or OxPhos independently disrupt circadian rhythms in these cells.
| S-EPMC10680562 | biostudies-literature
Project description: Not available
| S-EPMC6468406 | biostudies-literature
Project description:BackgroundSurges of COVID-19 infections have led to insufficient supply of mechanical ventilators (MV), resulting in rationing of MV care. In-parallel, co-mechanical ventilation (Co-MV) of multiple patients is a potential solution. However, due to lack of testing, there is currently no means to match ventilation requirements or patients, with no guidelines to date. In this research, we have developed a model-based method for patient matching for pressure control mode MV.MethodsThe model-based method uses a single-compartment lung model (SCM) to simulate the resultant tidal volume of patient pairs at a set ventilation setting. If both patients meet specified safe ventilation criteria under similar ventilation settings, the actual mechanical ventilator settings for Co-MV are determined via simulation using a double-compartment lung model (DCM). This method allows clinicians to analyse Co-MV in silico, before clinical implementation.ResultsThe proposed method demonstrates successful patient matching and MV setting in a model-based simulation as well as good discrimination to avoid mismatched patient pairs. The pairing process is based on model-based, patient-specific respiratory mechanics identified from measured data to provide useful information for guiding care. Specifically, the matching is performed via estimation of MV delivered tidal volume (mL/kg) based on patient-specific respiratory mechanics. This information can provide insights for the clinicians to evaluate the subsequent effects of Co-MV. In addition, it was also found that Co-MV patients with highly restrictive respiratory mechanics and obese patients must be performed with extra care.ConclusionThis approach allows clinicians to analyse patient matching in a virtual environment without patient risk. The approach is tested in simulation, but the results justify the necessary clinical validation in human trials.
| S-EPMC8826717 | biostudies-literature
Project description:Ultraviolet B radiation (UVB) is an environmental complete carcinogen, which induces and promotes keratinocyte carcinomas, the most common human malignancies. UVB induces the formation of cyclobutane pyrimidine dimers (CPDs). Repairing CPDs through nucleotide excision repair is slow and error-prone in placental mammals. In addition to the mutagenic and malignancy-inducing effects, UVB also elicits poorly understood complex metabolic changes in keratinocytes, possibly through CPDs. To determine the effects of CPDs, CPD-photolyase was overexpressed in keratinocytes using an N1-methyl pseudouridine-containing in vitro-transcribed mRNA. CPD-photolyase, which is normally not present in placental mammals, can efficiently and rapidly repair CPDs to block signaling pathways elicited by CPDs. Keratinocytes surviving UVB irradiation turn hypermetabolic. We show that CPD-evoked mitochondrial reactive oxygen species production, followed by the activation of several energy sensor enzymes, including sirtuins, AMPK, mTORC1, mTORC2, p53, and ATM, is responsible for the compensatory metabolic adaptations in keratinocytes surviving UVB irradiation. Compensatory metabolic changes consist of enhanced glycolytic flux, Szent-Györgyi-Krebs cycle, and terminal oxidation. Furthermore, mitochondrial fusion, mitochondrial biogenesis, and lipophagy characterize compensatory hypermetabolism in UVB-exposed keratinocytes. These properties not only support the survival of keratinocytes, but also contribute to UVB-induced differentiation of keratinocytes. Our results indicate that CPD-dependent signaling acutely maintains skin integrity by supporting cellular energy metabolism.
| S-EPMC7708942 | biostudies-literature
Project description:Background: We investigated the ability of a novel stand-alone, smartphone-based system, the cvrPhone, in estimating the minute ventilation (MV) from body surface electrocardiographic (ECG) signals. Methods: Twelve lead ECG signals were collected from anesthetized and mechanically ventilated swine (n = 9) using standard surface electrodes and the cvrPhone. The tidal volume delivered to the animals was varied between 0, 250, 500, and 750 mL at respiration rates of 6 and 14 breaths/min. MV estimates were determined by the cvrPhone and were compared with the delivered ones. Results: The median relative estimation errors were 17%, -4%, 35%, -3%, -9%, and 1%, for true MVs of 1,500, 3,000, 3,500, 4,500, 7,000, and 10,500 breaths*mL/min, respectively. The MV estimates at each of the settings were significantly different from each other (p < 0.05). Conclusions: We have demonstrated that accurate MV estimations can be derived from standard body surface ECG signals, using a smartphone.
| S-EPMC8742262 | biostudies-literature
Project description:IntroductionCurrent treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized.Materials and methodsContraction was recorded in pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized to record PA pressure. Ventilation and perfusion were analyzed by micro-CT-SPECT images in rats with pulmonary fibrosis induced by bleomycin.ResultsThe PDE5 inhibitor sildenafil and the sGC stimulator riociguat similarly inhibited HPV in vitro and in vivo. Riociguat was more effective as vasodilator in isolated rat and human PA than sildenafil. Riociguat was ≈3-fold more potent under hypoxic conditions and it markedly inhibited HPV in vivo at a dose that barely affected the thromboxane A2 (TXA2) mimetic U46619-induced pressor responses. Pulmonary fibrosis was associated with V'/Q' uncoupling and riociguat did not affect the V'/Q' ratio.ConclusionPDE5 inhibitors and sGC stimulators show a different vasodilator profile. Riociguat was highly effective and potentiated by hypoxia in rat and human PA. In vivo, riociguat preferentially inhibited hypoxic than non-hypoxic vasoconstriction. However, it did not worsen V'/Q' coupling in a rat model of pulmonary fibrosis.
| S-EPMC5783366 | biostudies-literature
Project description: Not available
| S-EPMC6444653 | biostudies-literature
Project description:BackgroundINTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery.MethodsSingle-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia.ResultsOf 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group.ConclusionsWe could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery.Trial registrationNCT04599491 (clinicaltrials.gov).
| S-EPMC10446221 | biostudies-literature