Room Air Group Research Articles

A novel circRNA-miRNA-mRNA regulatory axis as a sex-specific biological variable in Bronchopulmonary Dysplasia

Abstract Babies born prematurely with gestational age < 28 weeks usually develop a severe pulmonary complication called Bronchopulmonary Dysplasia (BPD) in response to hyperoxia. BPD is a sexually dimorphic pediatric disease with no curative options. Several micro RNAs (miRNAs) are implicated in BPD and are expressed differentially in males and females. Circular (circ) RNAs serve as sponges for their dedicated miRNAs to influence transcription and translation. We tested the dimorphism of these circular RNAs in BPD to assess their biological significance and unravel a circRNA-miRNA-mRNA regulatory axis in response to hyperoxia. Our RNA-Sequencing assay identified approximately 33 000 circRNAs at the alveolar stage of development with only a handful of them being expressed differentially between males and females in the control room air (RA) and hyperoxia-treated (BPD) groups. One circRNA i.e circNfix was found to be associated with miR204-5p that targets the downstream mRNA target Ntrk2. To prove that circNfix regulates Ntrk2, we silenced circNfix using a GapmeR and found that Ntrk2 was also suppressed, leading to an improved alveolar phenotype in BPD male pups. From the results of our study, we can propose circNfix and Ntrk2 as novel key regulators in the pathogenesis and sexual dimorphism of BPD, while simultaneously proposing the use of circNfix GapmeR towards a potential therapeutic application.

Transdermal carbon dioxide may accelerate hoof growth in healthy, sound horses in a short-term, randomized, controlled clinical trial.

Slow hoof growth poses a clinical challenge when hoof wear exceeds natural growth. Many treatment options have been reported without controlled prospective trials. The objective of this study was to evaluate the effect of transdermal CO2 on the rate of growth in treated hooves. A prospective, randomized, blinded, crossover study of 14 Warmblood mares. Horses were randomly assigned a number and allocated for treatment of the front feet with room air or CO2 for 30 minutes 3 times per week, and groups were switched after 5 weeks. Hoof growth was measured on the dorsal midline and the quarters of each front foot. The distance from coronary band to lines made on the hoof wall was measured at the beginning, middle, and end of the study. The percentage of change in length at each location relative to baseline was evaluated at 5 weeks and 10 weeks using nonparametric analyses. All treatments were successfully administered. The left front medial (P = .028) and right front lateral (P = .03) sites of the CO2-treated hooves increased growth compared to the room air group at the 5-week point. The results of this study suggest that repeated, noninvasive transdermal application of CO2 may accelerate hoof growth in normal horses over a 5-week treatment period. This study suggests that transdermal CO2 may increase the rate of hoof growth in normal horses. The mechanism of action of this treatment is unclear, and further studies are required to fully elucidate the potential effects.

The Characteristics and Two-Year Neurodevelopmental Outcomes of Home Oxygen Therapy among Preterm Infants with Bronchopulmonary Dysplasia: A Retrospective Study in a Medical Center in Taiwan.

Home oxygen therapy (HOT) is frequently used as a therapeutic strategy for children experiencing chronic oxygen dependency associated with bronchopulmonary dysplasia (BPD). Recent studies have highlighted substantial variations in the characteristics and outcomes of infants requiring oxygen, primarily due to the absence of a consensus on the management of HOT in infants with BPD. We conducted this retrospective study and reviewed the medical records of extremely and very preterm infants who were diagnosed with BPD in a tertiary center in northern Taiwan from January 2020 to September 2021. Their neurodevelopmental outcomes were evaluated at 18 to 24 months of corrected age. A total of 134 patients diagnosed with BPD were divided into a HOT group (n = 39) and a room air group (n = 95). The children in the HOT group had a higher incidence of hemodynamic significant patent ductus arteriosus (PDA) (p = 0.005) and PDA ligation (p = 0.004), high-frequency oscillatory ventilation (p < 0.001), nitrogen oxide inhalation (p < 0.001), pulmonary hypertension (p = 0.01), and longer invasive ventilation (p < 0.001), as well as longer hospitalization (p < 0.001). A multivariate logistic regression model demonstrated that prolonged invasive ventilation (OR = 1.032, 95% CI 0.984-1.020, p = 0.001) was correlated with oxygen dependency in children. Infants with BPD born at advanced gestational age (OR = 0.760, 95%CI 0.582-0.992, p = 0.044) had a decreasing risk of requiring HOT. The children in the HOT group had a higher incidence of emergency room visits (p < 0.001) and re-hospitalization (p = 0.007) within one year of corrected age. The neurodevelopmental outcomes revealed the HOT group had an increasing portion of moderate to severe cognitive delay (18.2% vs. 3.7%, p = 0.009) and moderate to severe language delay (24.2% vs. 6.1%, p = 0.006) at 18 to 24 months of corrected age. In conclusion, infants with BPD necessitating HOT required prolonged invasive ventilation during hospitalization and exhibited a greater prevalence of unfavorable neurodevelopmental outcomes at 18 to 24 months of corrected age as well.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Comparison of Two Methods for Weaning from Nasal Continuous Positive Airway Pressure via the Cyclic Use of High-Flow Nasal Cannula or Room Air in Preterm Infants.

Nasal continuous positive airway pressure (NCPAP) is extensively used for preterm infants experiencing respiratory distress syndrome (RDS). Weaning from NCPAP includes direct weaning or gradually extending room air exposure. However, a high-flow nasal cannula (HFNC) is an alternative weaning method. Therefore, this study evaluated the clinical outcomes of HFNC and progressively increasing room air duration as weaning strategies. This study enrolled 46 preterm infants with RDS receiving NCPAP support who underwent the cyclic use of NCPAP and HFNC weaning protocol as the HFNC group; a retrospective analysis included 87 preterm infants weaned from NCPAP by gradually extending room air duration as the room air group. Differences in clinical conditions, complications, and short-term outcomes between the weaning methods were compared. The mean post-menstrual age at initiating NCPAP weaning was lower in the room air group than in the HFNC group (mean ± SD, 35.2 ± 2.3 weeks vs. 33.2 ± 2.5 weeks, p < 0.001). Hospital stay duration and total respiratory therapy days were longer in the HFNC group (96 ± 38 days and 80 ± 37 days, respectively) than in the room air group (78 ± 28 days and 56 ± 25 days, respectively), with p-values of 0.006 and <0.001. In conclusion, employing HFNC for weaning from NCPAP resulted in longer hospital admissions and respiratory therapy days than the room air method. However, further studies with a larger sample size are warranted for a more comprehensive evaluation, given the limited number of enrolled patients.

Pde5 Inhibition Reduced Blood Pressure and Alleviated Target Organ Damage in Chronic Intermittent Hypoxia.

The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea-induced damage remains unclear. Our study aimed to investigate the role of Pde5 in the chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n = 48) and Pde5 knockout (Pde5 -/- ) mice (n = 24) were randomly assigned to CIH group and room air group. After 6 weeks, some WT mice (n = 24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function. We collected organs from each group of mice and measured their physical indicators. Histochemical staining was used to explore the size of cardiomyocyte and fibrosis area of various organs. Cyclic guanosine monophosphate and malondialdehyde concentrations in serum were measured by ELISA assay. Compared with the RA-treated group, the 6-week CIH resulted in a significant increase in blood pressure, altered heart structure, and reduced serum cyclic guanosine monophosphate in WT mice. Pde5 -/- mice and sildenafil intragastric administration significantly reduced systolic blood pressure in CIH condition and attenuated the damage of target organs. In CIH model, we found that the cardiomyocyte size and fibrosis area of heart and kidney significantly reduced in Pde5 -/- groups. Besides, endogenous and exogenous inhibition of Pde5 reduced malondialdehyde level and inflammatory and oxidative stress markers expression in CIH condition. In this study, we found that Pde5 inhibition could reduce blood pressure and alleviate target organ damage in the CIH model, which may be mediated through the oxidative stress pathway.

Room air versus 100% oxygen for delivery room resuscitation of preterm neonates in low resource settings: A randomised, blinded, controlled trial.

International Liaison Committee on Resuscitation (ILCOR-2020) report recommend starting delivery room resuscitation of all preterm neonates of <35 weeks' gestation with 21-30% oxygen. However, the correct initial oxygen concentration for resuscitation of preterm neonates in delivery room is inconclusive. In this blinded, randomised, controlled trial, we compared room air with 100% oxygen for oxidative stress and clinical outcomes in delivery room resuscitation of preterm neonates. Preterm neonates 28-33 weeks' gestation requiring positive pressure ventilation at birth were randomly allocated to room air or 100% oxygen. Investigators, outcome assessors and data analysts were blinded. Rescue 100% oxygen was used whenever trial gas failed (need for positive pressure ventilation >60 s or chest compression). Plasma 8-isoprostane levels at 4 h of age. mortality by discharge, bronchopulmonary dysplasia, retinopathy of prematurity and neurological status at 40 weeks post-menstrual age. All subjects were followed till discharge. Intention to treat analysis was carried out. A total of 124 neonates were randomised to room air (n = 59) or 100% oxygen (n = 65). Isoprostane level at 4 h was similar in both the groups (median (interquartile range): 280 (180-430) vs. 250 (173-360) pg/mL, P = 0.47). No difference was observed in mortality and other clinical outcomes. Room air group had higher treatment failures (27 (46%) vs. 16 (25%); relative risk (RR) 1.9 (1.1-3.1)) and took longer time to establish regular respiration (230 ± 231 vs. 182 ± 261, mean difference = 48 (40, 136) seconds). In preterm neonates 28-33 weeks' gestation requiring resuscitation in the delivery room, room air (21%) is not the correct concentration to initiate resuscitation. Larger controlled trials involving multiple centres in low- and middle-income countries are immediately required for a conclusive answer.

IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients.

The management of hospitalized COVID-19 patients depends largely on controlling the intensified inflammatory response known as the cytokine storm. Candidate inflammatory cytokines can serve as new biomarkers for the management of hospitalized COVID-19 patients. Patients (80) were recruited into three groups: room air (RA), oxygen (OX) and mechanical ventilator (MV). Blood analysis was performed for RBC, WBC, Hb, Platelets, serum albumin and creatinine, INR, PTT, and hematocrit. ELISA was used to quantify a panel of inflammatory mediators including GM-SCF, IFN-α, IFNγ, IL-1β, IL-1R, IL-2, IL-2Ra, IL-6, IL-8, IL-10, IL-12p70, IL-13, MCP-1, MIP-1a, and TNF-α. Correlations between laboratory results and the levels of circulating inflammation mediators were investigated. Patients on MV had low RBC, Hb, albumin, and HCT and high WBC count, PTT, and INR when compared to RA and OX groups. A statistical positive correlation was found between WBC and the levels of IL-6 and MCP-1. RBCs correlated negatively with IL-6 and IL-10 and positively with IL-8. Higher TNF-α correlated with lower platelet counts while higher levels of IL-1Rα and IL-10 were associated with lower Hb levels. Increases in IFN-γ and TNF-α were indicative of compromised kidney functions as creatinine levels increased significantly. Most significant correlations were found between IL-6 and lab results, showing positive correlation with WBC and INR, and negative correlation with RBC, albumin, and HCT. Having the most significant correlations, IL-6 high levels in mechanically ventilated patients were shown to affect laboratory results, and, therefore, is suggested as a severity biomarker of COVID-19.

DETERMINATION OF TREATMENT TIME AND EFFICACY WITH OXYGEN IN EXPERIMENTAL METHEMOGLOBINEMIA MODEL

Introduction: Methemoglobin, an abnormal form of hemoglobin, is one of the causes that should be considered primarily in severe central cyanosis. Methylene blue and ascorbic acid are used as the first-line therapies in methemoglobinemia. Experience with the use of oxygen therapy is not sufficient to conclude the duration of therapy. The aim of the present study is to find out the effects of oxygen therapy on drug or toxic agent-induced methemoglobinemia. Material and Method: First group rats (n=6) were administered 100 mg/kg prilocaine intraperitoneally, and the rats were kept at room temperature. The second group of oxygen group rats (n=6) were administered 100% oxygen at 10 liters/min. All rats were observed for 180 minutes, and blood gas and biochemical analyses were performed at the end of the experiment period. Results: Fifty percent of the rats in the room air group (n=3) died spontaneously at the end of the trial period, while all rats in the oxygen group (n=6) survived to the end of the trial period. When evaluated in terms of survival, a statistical difference was found between the groups (p &lt;0.05). In addition, although there was a significant difference in oxygen saturation levels between the groups (p &lt;0.05), there was no significant increase in partial arterial oxygen pressure, the primary determinant of oxygenation. Conclusion: This study revealed that rats are not suitable for this type of experimental study. Prilocaine doses did not cause high levels of methemoglobinemia due to mortality, so the goal and target could not be met. It has been concluded that this study can serve as a guide for choosing methodologies to be employed in planned future investigations of the topic.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UAgas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.

Home oxygen use and 1-year outcome among preterm infants with bronchopulmonary dysplasia discharged from a Chinese regional NICU.

ObjectiveThis study aims to compare the clinical characteristics and 1-year outcomes of preterm infants with bronchopulmonary dysplasia (BPD) who were discharged on supplemental oxygen or room air.Materials and MethodsThe preterm infants (born <32 weeks’ gestation, birth weight ≤1,250 g) diagnosed with BPD and admitted between January 2020 and December 2020 were enrolled. The clinical data during hospitalization were collected through the hospital’s electronic record system. The outcomes after discharge were acquired from the outpatient system and through telephonic interviews.ResultsOf the 87 preterm infants diagnosed with BPD, 81 infants survived until discharge. The 81 infants were divided into the home oxygen group (n = 29) and room air group (n = 52) according to supplemental oxygen or not at discharge. Infants in the home oxygen group were more likely to receive postnatal systemic steroids and higher ventilation settings at 36 weeks’ PMA. There was one patient in each group who died before 1 year corrected age, respectively. All the infants had successfully weaned off oxygen eventually during the first year. The median duration of home oxygen therapy was 25 (7,42) days. Readmission occurred in 49 (64.5%) infants. Readmissions for infants with home oxygen were more often related to respiratory disease. In addition, wheezing disorders and home inhalation occurred more frequently in the home oxygen group (p = 0.022, p = 0.004). Although the incidence of underweight at 1 year corrected age was higher in the room air group (10.0 vs. 3.8%), there was no significant difference (p = 0.620). The rate of neurodevelopmental impairment was similar between these two groups (26.0 vs. 30.8%, p = 0.659).ConclusionsIt was the first study focused on preterm infants with BPD receiving home oxygen in China. Infants with home oxygen were more likely to have respiratory problems after discharge from NICU. Home oxygen use was not associated with more readmission for infants with BPD, and no difference was found in neurodevelopmental impairment and growth outcome.

Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner: pilot study.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse during sleep, which induces chronic intermittent hypoxia (CIH). CIH results in low-grade inflammation, sympathetic overactivity, and oxidative stress. Nevertheless, it remains unclear how exposure to CIH affects olfaction. The purpose of this study was, therefore, to investigate the cytotoxic effects of CIH exposure on mouse olfactory epithelium and the underlying pathophysiology involved. Mice were randomly divided into four groups: Youth mouse (You) + room air (RA), You + intermittent hypoxia (IH), Elderly mouse (Eld) + RA, and Eld + IH (n = 6 mice/group). Mice in the two hypoxia groups were exposed to CIH. The control condition involved exposure to room air (RA) for 4weeks. Olfactory neuroepithelium was harvested for histologic examination, gene ontology analysis, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. Based on qRT-PCR analysis, olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL mRNA levels were lower, whereas NGFR, CNPase, NGFRAP1, NeuN, and MAP-2 mRNA levels were higher in the You + IH group than in the You + RA group. Olfactory receptor-regulated genes, neurogenesis-related genes and immunohistochemical results were altered in nasal neuroepithelium under CIH exposure. Based on genetic and cytologic analysis, CIH impacted the olfactory neuroepithelium in an age-dependent manner. Our findings suggest that CIH-induced damage to the olfactory neuroepithelium may induce more severe change in the youth than in the elderly.

Effect of long-duration oxygen vs room air during labor on umbilical cord venous partial pressure of oxygen: a randomized controlled trial

There are limited data to guide the duration and dose of oxygen supplementation for pregnant women undergoing labor. To assess the effect of maternal long-duration high-concentration oxygen administration during labor on umbilical cord venous partial pressure of oxygen. This randomized clinical trial was conducted between January and October of 2021 in the obstetrics wards of 3 tertiary teaching hospitals in Beijing, China. Women undergoing the latent phase of labor with no existing medical conditions or obstetrical complications who were admitted for delivery were eligible. The women who met inclusion criteria with category I fetal heart rate tracings in labor were randomized in a 1:1 ratio to oxygen or room air. The oxygen group received 10 L of oxygen per minute by simple, tight-fitting face mask until delivery. The room-air group received room air only, without a face mask. The primary outcome was the umbilical cord venous partial pressure of oxygen. A total of 661 women were screened, and 521 were excluded; 140 participants with category I fetal heart rate tracings were enrolled and randomized to oxygen (N=70) or room air (N=70). A total of 135 women with valid paired umbilical cord venous and arterial gas values were included in the umbilical cord venous partial pressure of oxygen and arterial pH analyses. All 140 women were included in the fetal heart rate tracings analysis. Baseline characteristics were similar between the oxygen and room-air groups. The duration of oxygen exposure was approximately 322±147 minutes. There were no differences between the oxygen and room-air groups in the umbilical cord venous partial pressure of oxygen (mean difference, 1.1 mm Hg; 95% confidence interval,-1.0 to 3.2; P=.318) or the proportion of participants with category II fetal heart rate tracings (81.4% vs 78.6%; relative risk, 1.04; 95% confidence interval, 0.88-1.22; P=.672). However, the umbilical cord arterial pH was significantly lower in the oxygen group than in the room-air group (median, 7.23; interquartile range, 7.20-7.27 vs median 7.27; interquartile range, 7.20-7.30; P=.005). Maternal long-duration high-concentration oxygen administration during labor did not affect either the umbilical cord venous partial pressure of oxygen or fetal heart rate pattern distribution but resulted in a deterioration of the umbilical cord arterial pH at birth.

The Role of Carbon Dioxide in the Rat Acute Stroke Penumbra.

PurposeThe vasodilatory response to inhaled CO2 occurs in the acute stroke ischemic penumbra and may be a potential therapeutic modality.MethodsTwenty-two Sprague-Dawley rats were subjected to 90-min occlusion of the M2 segment of the middle cerebral artery (M2CAO) by endovascular technique. The animals were administered different C02 concentrations and scanned serially with 9.4 T MRI. Infarct tissue was determined by diffusion-weighted imaging (DWI) and hypoperfused tissue was determined by arterial spin labeling (PWI).Results4 animals were administered room air (RA)+ 6% CO2 (group 1), 6 animals RA+12% CO2 (Group 2) and 4 animals only RA (group 3). In the rats with CO2 administered (groups 1 and 2), the DWI lesion to cerebral hypoperfusion volume ratio (SD) at pre-CO2 administration, was 0.145(0.168), which increased to 0.708(0.731) during CO2 administration and reduced to 0.533(0.527) post-CO2 administration. In 9 of 10 rats the hypoperfused volume decreased when CO2 was administered. When CO2 was stopped the hypoperfused volume became larger again. Administration of RA+12% CO2 (Group 2) decreased the volume of CBF hypoperfusion significantly compared to the control group (95%CI: 0.084 ± 0.0213, p = 0.004).ConclusionInhaled CO2 appears to reduce the size of the hypoperfused tissue volume during acute stroke and may be a potential modality for treatment of acute ischemic stroke. These findings will nonetheless need to be validated in a larger cohort in other centers.

Cardiac Arrhythmias and COVID-19: Correlation With Disease Severity.

BackgroundCardiac arrhythmia is one of the life-threatening cardiovascular complications commonly reported in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the association between cardiac arrhythmias and disease severity based on oxygen requirement.MethodsIn this retrospective observational chart review-based study we recruited 396 patients hospitalized with COVID-19 from March 2020 to May 2020 from two regional medical centers in New Jersey, USA. Patients’ baseline characteristics, secondary diagnoses, and laboratory findings were manually extracted and compared among two groups: patients with cardiac arrhythmias and those without. Poisson regression analysis was used to evaluate the correlation of cardiac arrhythmias and increased oxygen requirement, which are: room air (RA), nasal cannula (NC), high flow nasal cannula (HFNC), and bi-level positive airway pressure ventilation or invasive mechanical ventilation (BIPAP/MV).ResultsThe demographic characteristics of the patients were: aged 61 +/- 18.7 years (mean +/- standard deviation); with 56% being male, and 44.9% of African American race. There were 16% patients on RA, 40% on NC, 15% on HFNC, and 29% on BIPAP/MV. The incidence of cardiac arrhythmias was 36.7% (20% pulseless electrical activity (PEA), 13.5% atrial fibrillation (AF). 56% of AF was new-onset arrhythmia. Compared to the RA group, the risk of cardiac arrhythmias was significantly higher in BIPAP/MV (OR 3.3; 95% CI 1.8 - 6.2, p <0.001) and HFNC (OR 2.9; 95% CI 1.5-5.7, p0.001), but not in NC group (OR 0.95; 95% CI 0.4-1.8, p0.89).Compared to patients without arrhythmias, patients with arrhythmias were older (mean age 71 vs. 56 years, p <0.001) and had more comorbidities (Charlson comorbidity index (CCI), 4.7 vs. 2.9, p <0.001). The continued therapy of angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers did not seem to be associated with increased or decreased risk of cardiac arrhythmias.ConclusionThe incidence of cardiac arrhythmias among hospitalized COVID-19 patients was 36.7% with PEA being common in patients who succumbed to death, and AF in those patients who survived. The incidence of cardiac arrhythmias positively correlated with disease severity based on oxygen requirement and was higher among patients requiring HFNC or BIPAP/MV.

Abstract P446: Cyclophilin D Inhibition Rescues Cardiac Function And Electron Transport Chain Assembly And Activity In Hypoxia Exposed Neonatal Mice

Introduction: Mitochondria play a critical role in cardiac myocyte physiology and differentiation. Hypoxia decreases cardiac function. Changes in embryonic heart metabolism at the level of the electron transport chain (ETC) are regulated by a chaperone protein known as cyclophilin D (CypD). Inhibition of CypD with chemicals such as cyclosporin A (CsA) and N-methyl-4-isoleucine cyclosporin (NIM811) leads to more complex mitochondrial structure and effective oxidative phosphorylation. Hypothesis: Inhibition of CypD with CsA or NIM811 will rescue the detrimental effects of hypoxia on cardiac function and on ETC assembly and activity. Methods: Mice were exposed to continuous hypoxia (12% oxygen) immediately before birth (gestational age E19.5) to postnatal day 7 (P7). Hypoxic mice received no treatment (No Tx) or intraperitoneal injections 10mg/kg of vehicle (VEH), CsA, or NIM811 from P1 to P6. Litters of mice born into room air served as controls. On P7, mice were anesthetized and underwent echocardiography and/or hearts were harvested for mitochondrial isolation. Enzymatic activity of ETC complexes was quantified using spectrophotometry and normalized to total protein. To measure physical assembly of complex I &amp; V of the ETC, high resolution clear native polyacrylamide gel electrophoresis (HCRN PAGE) followed by in-gel assays were utilized using appropriate protein loading controls. Results: Cardiac ejection fraction was decreased in hypoxic No Tx (P&lt;0.0001) and VEH (P&lt;0.0001), but was rescued by CsA or NIM811 when compared to room air controls (P&gt;0.05). Heart weight to body weight ratio was increased in No Tx and VEH groups (P&lt; 0.0001) and rescued in the CsA and NIM811 groups when compared to room air controls (P&gt;0.05). Complex I enzymatic activity was rescued with treatment with CsA and NIM811. HCRN PAGE followed by in-gel ETC complex assay demonstrated assembly of complexes I and V into dimers and tetramer in the room air, CsA, and NIM811 groups that was not seen in the No Tx and VEH groups. Conclusion: Pharmacologic inhibition of CypD reversed the effects of hypoxia on cardiac function and ETC activity and assembly in the neonatal heart. Our studies may help develop therapies to treat neonatal cardiomyopathies and the effects of hypoxia on the neonatal heart.

A Novel Procedure for the Management of Severe Hyphema after Glaucoma Filtering Surgery: Air-Blood Exchange under a Slit-Lamp Biomicroscopy.

Background and Objectives: This study introduces a novel office-based procedure involving air–blood exchange under a slit-lamp microscope for treatment of severe hyphema after filtering surgery. Materials and Methods: This retrospective study enrolled 17 patients (17 eyes) with a diagnosis of primary open-angle glaucoma with severe hyphema (≥4-mm height) after filtering surgery. All patients were treated with air–blood exchange under a slit-lamp using room air (12 patients) or 12% perfluoropropane (C3F8; five patients). Results: The procedures were successful in all 17 patients; they exhibited clear visual axes without complications during follow-up. In the room air group, the mean visual acuity (VA) and hyphema height significantly improved from 1.70 ± 1.07 LogMAR and 5.75 ± 1.14 mm before the procedure to 0.67 ± 0.18 LogMAR and 2.83 ± 0.54 mm after the procedure (p = 0.004; p < 0.001). In the C3F8 group, the mean VA showed a trend, though not significant, for improvement from 1.70 ± 1.10 LogMAR to 0.70 ± 0.19 LogMAR (p = 0.08); the mean hyphema height showed a trend for improvement from 5.40 ± 0.96 mm to 3.30 ± 0.45 mm. Compared with the C3F8 group, the room air group showed the same efficacy with a shorter VA recovery time. Conclusions: “Air–blood exchange under a slit-lamp using room air” is a convenient, rapid, inexpensive, and effective treatment option for severe hyphema after filtering surgery, and may reduce the risk of failure of filtering surgery.

Impact of Long-chain Polyunsaturated Fatty Acids on Hyperoxia-Induced Lung Injury in Neonatal Murine Model

ObjectivesReduced levels of long chain-polyunsaturated fatty acids (LCPUFAs) in preterm infants are associated with several neonatal morbidities, including bronchopulmonary dysplasia (BPD). We hypothesized that LCPUFA supplementation would attenuate hyperoxia-induced lung injury in a neonatal mouse model, and we tested our hypothesis in 40%O2-induced-lung injury in neonatal murine model. MethodsC57BL/6 WT dams were allowed to deliver naturally, and pups were randomized within 12 hours of birth to either hyperoxia (H, 40% O2) or room air (RA) for 10 days. To study the effect of LCPUFAs on hyperoxia-induced lung injury, the pups were randomized to the following groups: 1) RA (vehicle), 2) H (vehicle), 3) H + AA (120mg/kg/day), 4) H + DHA (60mg/kg/day), and 5) H + AA: DHA at 120mg/kg/day and 60mg/kg/day, respectively, maintaining a 2:1 ratio. Mice were gavage fed once daily 50 ul/g body weight from day 1–9. On day 10, the mice were sacrificed, and the lungs were removed for morphometric analyses. Mean Linear Intercept (MLI), Mean Septal Thickness (MST), and Radial Alveolar Count (RAC) were quantified and analyzed using R software and data was shown as mean ± SD. ResultsCompared to RA group, mice in hyperoxia groups showed a significant increase in MLI intercept (RA vs H = 47.75 ± 2.02 vs 56.24 ± 5.54, p < 0.01) and MST (RA vs H = 7.33 ± 0.45 vs 7.88 ± 0.70, p < 0.01), and a significant decrease in RAC (RA vs H = 12.93 ± 0.82 vs 10.26 ± 1, p < 0.01). Compared to H alone, AA: DHA resulted in a significant reduction in hyperoxia-induced MST (H vs H + AA: DHA = 8.70 ± 0.44 vs 6.94 ± 0.74, p < 0.001) and improved hyperoxia-induced reduction in RAC (H vs H + AA: DHA = 9.7 ± 0.9 vs 12.0 ± 1.4, p < 0.001). Noteworthy, while AA decreased hyperoxia-induced MST (H vs H + AA = 8.7 ± 0.4 vs 6.9 ± 0.6, p < 0.001), it significantly increased MLI (H vs H + AA = 58.76 ± 5.9 vs 71.19 ± 6.1, p < 0.001). ConclusionsWe reproduced lung injury in a neonatal murine model using 40% O2 and showed a significant increase in MLI, MST, and decreased RAC. The data also demonstrate that LCPUFAs acts distinctively, and specific fatty acids alone or in combination have contrasting effects. Whether the observed changes are also associated with the inflammatory response needs to be investigated further to better understand the impact of LCPUFAs in hyperoxia-induced lung injury and inflammation. Funding SourcesCharles H. and Judy H. Family Infant Health Research Program.

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia.

PurposeCognitive impairment is an important complication of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), the main pathophysiological characteristics of OSA, is closely related to cognitive dysfunction and may be mediated by alpha-7 nicotinic acetylcholine receptors (α7nAChR). This study investigated the effects and clarified the mechanisms of α7nAChR on the cognitive function of mice with CIH.MethodsThirty CD-1 mice were randomly divided into room air (RA), CIH-2 weeks (CIH2W), and CIH-4 weeks (CIH4W) groups. Cognitive function was evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests after exposure. Then, 104 CD-1 mice were exposed to CIH for 4 weeks and randomly divided into four groups: CIH4W (control), with dimethyl sulfoxide (DMSO) (sham), with α7nAChR-specific agonist PNU-282987 (PNU), and with α7nAChR-specific inhibitor methyllycaconitine and PNU-282987 (MLA+PNU). In addition to the evaluation of cognitive function, apoptotic bodies in the hippocampus were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, changes in p-CREB and BDNF were detected by immunohistochemistry, while those of ERK1/2, CREB, PGC-1α, FNDC5, and BDNF were detected by Western blotting in the hippocampal tissues of the mice.ResultsCompared to the CIH2W and RA groups, the CIH4W group showed cognitive dysfunction in the NOR and MWM tests. The changes in cognitive dysfunction were alleviated by PNU-282987; furthermore, MLA pretreatment offset the effect. In hippocampal tissues, TUNEL assays showed decreased apoptotic cells, immunohistochemical staining showed increased expressions of p-CREB and BDNF. The expression levels of p-ERK1/2/t-ERK1/2, p-CREB/t-CREB, PGC-1α, FNDC5, and BDNF were increased after PNU-282987 injection.ConclusionFour weeks of CIH caused cognitive dysfunction in mice. Activating α7nAChR might ameliorate this dysfunction by upregulating the ERK1/2/CREB signaling pathway; enhancing PGC-1α, FNDC5, and BDNF expression levels; and reducing cell apoptosis in the hippocampal tissue of mice.

Hypercapnia‐evoked Chronic Stress Alters IL‐1β Levels in Brain Respiratory Chemoreceptor Regions

Chronic stress often elicits neuronal, hormonal, and immune responses. Long term hypercapnia is a respiratory stressor linked with sleep apnea, sudden infant death syndrome (SIDS) and chronic obstructive pulmonary disease (COPD), however, mechanisms of central respiratory dysfunction in these conditions are unclear. We aimed to explore the neuroinflammatory responses to hypercapnia in key brain respiratory regions. We tested the hypothesis that long-term exposure to 8% CO2 activates the releaseof brain stress hormone corticosterone (CORT) in the circulation which may contribute to inflammation in brainstem circuits that regulate CO2-stimulated breathing. Age-matched adult male C57BL/6J mice (n=10 mice/group) were exposed to hypercapnia (8% CO2; balance room air) in the short-term (6 hours) or long-term (10 or 14 days), or room air (control) conditions.Following anesthesia, plasma samples were collected for corticosterone (CORT) assay and brain tissues including cerebellum, hypothalamus, the nucleus of the solitary tract (NTS), rostral and caudal retrotrapezoid nucleus (rRTN, cRTN) were micro-dissected and processed for cytokine assays. Plasma CORT levels were not different between hypercapnia and room air groups in the short-term, but a significantly higher CORT level (p < 0.01, 2 way ANOVA) was observed following 10 days of exposure to hypercapnia compared to control conditions. CORT level returned to baseline following 14 days of hypercapnia compared to control (14 days room air) conditions. In the brain, the pro-inflammatory cytokine interleukin-1β (IL-1β) was raised in the cerebellum (p < 0.01, 2 way ANOVA) following 6 hours but not 10 days of hypercapnia exposure, compared to control conditions. In the hypothalamus and cRTN, IL-1β was unaltered at the 6 hours time point, significantly upregulated (p < 0.05, p < 0.01, 2 way ANOVA) at 10 days of hypercapnia exposure, compared to controls. In these brain regions, IL-1β levels returned to baseline after 14 days hypercapnia exposure time point. There was no change in IL-1β in the rRTN and NTS following 6 hours, 10 days, and 14 days of hypercapnia, compared to controls. Taken together, the level of plasma CORT positively correlates to brain IL-1β during long-term hypercapnia. These results suggest that hypercapnia activates a physiological stress response, and the associated brain inflammation depends on the duration of hypercapnia exposure. We propose that the stress and inflammatory adaptive responses observed are part of compensatory mechanisms following long-term hypercapnia. The cellular source and underlying mechanisms of interactions between plasma CORT and brain IL-1β are under investigation.