ResearchPad - respiratory-conditions-disorder-and-diseases https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload]]> https://www.researchpad.co/article/N51034a10-0d22-497f-84f8-cbd530e51603 Right ventricular (RV) failure is a common endpoint in pulmonary hypertension. While most clinical and research efforts are focused on the RV, our research shows that the left ventricle undergoes bio‐mechanical and gene‐expression changes in response to RV pressure overload.

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<![CDATA[Thoracic gas compression during forced expiration is greater in men than women]]> https://www.researchpad.co/article/N756914ff-d54d-4bb6-804d-3378610abf91

Abstract

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p < .001). ∆FEF was greater in men at 25% of exhaled volume only (p < .05), whereas ∆VGC was systematically greater in men across the entire VC (main effect; p < .05). PALV was also greater in men throughout forced expiration (p < .01). Taken together, these findings demonstrate that men display more TGC, occurring early in forced expiration, likely due to greater expiratory pressures throughout the forced VC maneuver.

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<![CDATA[Urine biomarkers of renal renin–angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea]]> https://www.researchpad.co/article/Nd6d4c75b-de13-4e23-bea1-4ba941cda6a6

Abstract

Obstructive sleep apnea (OSA) may contribute to kidney injury by activation of the renin–angiotensin system (RAS), which is reduced by continuous positive airway pressure (CPAP) therapy. A biomarker in the urine that reflects renal RAS activity could identify patients at risk of kidney injury and monitor their response to CPAP therapy. Nine patients with OSA and six matched control subjects without OSA were recruited. Renal RAS activity was measured by the renovasoconstrictor response to Angiotensin II challenge, a validated marker of RAS activity, and urine samples were collected in all subjects at baseline and repeated in those with OSA following treatment with CPAP. A broad range (1,310) of urine analytes was measured including 26 associated with the RAS signaling pathway. The OSA group was a similar age and weight as the control group (48.7 ± 10.4 vs. 47.7 ± 9.3 yrs; BMI 36.9 ± 7.2 vs. 34.7 ± 2.5 kg/m2) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO2 87 ± 5.2 vs. 92.6 ± 1.1%). CPAP corrected OSA associated with a return of the renovasocontrictor response to Angiotensin II to control levels. Partial least squares (PLS) logistic regression analysis showed significant separation between pre‐ and post‐CPAP levels (p < .002) when all analytes were used, and a strong trend when only RAS‐associated analytes were used (p = .05). These findings support the concept that urine analytes may be used to identify OSA patients who are susceptible to kidney injury from OSA before renal function deteriorates and to monitor the impact of CPAP therapy on renal RAS activity.

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<![CDATA[Dexamethasone fails to improve bleomycin‐induced acute lung injury in mice]]> https://www.researchpad.co/article/N05b6e6f4-00f7-4b19-bd48-418665cf18da

Abstract

Acute respiratory distress syndrome (ARDS) features an exudative phase characterized by alveolar damage, lung edema and exacerbated inflammatory response. Given their anti‐inflammatory properties, the potential therapeutic effect of corticosteroids has been evaluated in ARDS clinical trials and experimental models of ALI. These studies produced contradictory results. Therefore, our aim was to investigate the effects of dexamethasone in an animal model of bleomycin‐induced acute lung injury and then to determine if the lack of response could be related to an impairment in repair ability of alveolar epithelial cells after injury. NMRI mice were challenged with bleomycin and then treated daily with dexamethasone or saline. Bronchoalveolar lavages (BAL) and lungs were collected for assessment of the inflammatory response and wet/dry ratio (lung edema) and for histological analyses. The effect of bleomycin and dexamethasone on wound repair was also evaluated in vitro on primary alveolar epithelial cell (ATII) cultures. Our data first showed that dexamethasone treatment did not reduce the weight loss or mortality rates induced by bleomycin. Although the TNF‐α level in BAL of bleomycin‐treated mice was reduced by dexamethasone, the neutrophil infiltration remained unchanged. Dexamethasone also failed to reduce lung edema and damage scores. Finally, bleomycin elicited a time‐ and dose‐dependent reduction in repair rates of ATII cell cultures. This inhibitory effect was further enhanced by dexamethasone, which also affected the expression of β3‐ and β6‐integrins, key proteins of alveolar repair. Altogether, our data indicate that the inability of dexamethasone to improve the resolution of ALI might be due to his deleterious effect on the alveolar epithelium repair.

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<![CDATA[Airway delivery of interferon‐γ overexpressing macrophages confers resistance to Mycobacterium avium infection in SCID mice]]> https://www.researchpad.co/article/5b294df6463d7e7cb9c5a7ed

Abstract

Mycobacterium avium (M. avium) causes significant pulmonary infection, especially in immunocompromised hosts. Alveolar macrophages (AMs) represent the first line of host defense against infection in the lung. Interferon gamma (IFNγ) activation of AMs enhances in vitro killing of pathogens such as M. avium. We hypothesized that airway delivery of AMs into the lungs of immunodeficient mice infected with M. avium will inhibit M. avium growth in the lung and that this macrophage function is in part IFNγ dependent. In this study, normal BALB/c and BALB/c SCID mice received M. avium intratracheally while on mechanical ventilation. After 30 days, M. avium numbers increased in a concentration‐dependent manner in SCID mice compared with normal BALB/c mice. Airway delivery of IFNγ‐activated BALB/c AMs or J774A.1 macrophages overexpressing IFNγ into the lungs of SCID mice resulted in a significant decrease in M. avium growth (P < 0.01, both comparisons) and limited dissemination to other organs. In addition, airway delivery of IFNγ activated AMs and macrophages overexpressing IFNγ increased the levels of IFNγ and TNFα in SCID mice. A similar protective effect against M. avium infection using J774A.1 macrophages overexpressing IFNγ was observed in IFNγ knockout mice. These data suggest that administration of IFNγ activated AMs or macrophages overexpressing IFNγ may partially restore local alveolar host defense against infections like M. avium, even in the presence of ongoing systemic immunosuppression.

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<![CDATA[Breathing 100% oxygen during water immersion improves postimmersion cardiovascular responses to orthostatic stress]]> https://www.researchpad.co/article/5bd40811d5eed0c48478697c

Abstract

Physiological compensation to postural stress is weakened after long‐duration water immersion (WI), thus predisposing individuals to orthostatic intolerance. This study was conducted to compare hemodynamic responses to postural stress following exposure to WI alone (Air WI), hyperbaric oxygen alone in a hyperbaric chamber (O2 HC), and WI combined with hyperbaric oxygen (O2 WI), all at a depth of 1.35 ATA, and to determine whether hyperbaric oxygen is protective of orthostatic tolerance. Thirty‐two healthy men underwent up to 15 min of 70° head‐up tilt (HUT) testing before and after a single 6‐h resting exposure to Air WI (N = 10), O2 HC (N = 12), or O2 WI (N = 10). Heart rate (HR), blood pressure (BP), cardiac output (Q), stroke volume (SV), forearm blood flow (FBF), and systemic and forearm vascular resistance (SVR and FVR) were measured. Although all subjects completed HUT before Air WI, three subjects reached presyncope after Air WI exposure at 10.4, 9.4, and 6.9 min. HUT time did not change after O2 WI or O2 HC exposures. Compared to preexposure responses, HR increased (+10 and +17%) and systolic BP (−13 and −8%), and SV (−16 and −23%) decreased during HUT after Air WI and O2 WI, respectively. In contrast, HR and SV did not change, and systolic (+5%) and diastolic BP (+10%) increased after O2 HC. Q decreased (−13 and −7%) and SVR increased (+12 and +20%) after O2 WI and O2 HC, respectively, whereas SVR decreased (−9%) after Air WI. Opposite patterns were evident following Air WI and O2 HC for FBF (−26 and +52%) and FVR (+28 and −30%). Therefore, breathing hyperbaric oxygen during WI may enhance post‐WI cardiovascular compensatory responses to orthostatic stress.

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<![CDATA[Exposure to electronic cigarette vapors affects pulmonary and systemic expression of circadian molecular clock genes]]> https://www.researchpad.co/article/5b444e16463d7e37cb68f0dc

Abstract

E‐cigarette use has exploded in the past years, especially among young adults and smokers desiring to quit. While concerns are mostly based on the presence of nicotine and flavors, pulmonary effects of propylene glycol and glycerol inhalation, the main solvents of e‐liquid have not been thoroughly investigated. In this preclinical study, mice were exposed 2 h daily for up to 8 weeks to vapors of propylene glycol and/or glycerol generated by an e‐cigarette. Lung transcriptome analysis revealed it affected the expression level of genes of the circadian molecular clock, despite causing no inflammatory response. Periodical sacrifices showed that the rhythmicity of these regulatory genes was indeed altered in the lungs, but also in the liver, kidney, skeletal muscle, and brain. E‐cigarette exposure also altered the expression of rhythmic genes (i.e., hspa1a and hspa1b), suggesting that alterations to the ‘clock genes’ could translate into systemic biological alterations. This study reveals that the major solvents used in e‐cigarettes propylene glycol and glycerol, not nicotine or flavors, have unsuspected effects on gene expression of the molecular clock that are to be taken seriously, especially considering the fundamental role of the circadian rhythm in health and disease.

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