Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin (ET)-1 is a potent vasoconstrictor peptide that modulates basal pulmonary vascular resistance (PVR) in the normal ovine fetus and contributes to high PVR after chronic intrauterine pulmonary hypertension. Although high PVR is present in premature lambs with severe hyaline membrane disease (HMD), whether ET-1 plays a role in the pathophysiology of experimental HMD is unknown. To test the hypothesis that ET-1 activity contributes to high PVR in the premature lamb with HMD, we studied the hemodynamic effects of a selective ET(A) receptor antagonist, BQ 123, in 10 animals (gestational age 125 d; 147 d=term). After baseline measurements, animals were intubated, treated with surfactant (Infasurf), and mechanically ventilated with a fraction of inspired oxygen of 1.00 for 8 h. Animals were treated with continuous infusions of either BQ 123 (1 mg/h; treatment group, n=5) or 1% DMSO (control; n=5). Plasma ET-1 levels progressively increased during prolonged ventilation with hyperoxia (0.8+/-0.1 pg/mL, baseline to 6.8+/-2.5 pg/mL, 8 h, p < 0.05). In comparison with control lambs, BQ 123 treatment caused a sustained reduction in pulmonary vascular resistance (0.55+/-0.04 mm Hg mL-(-1) min(-1), control versus 0.18+/-0.04 mm Hg mL(-1) min(-1), BQ 123, p < 0.05), increased left pulmonary artery blood flow (70+/-12 mL/min, control versus 194+/-28 mL/min, BQ 123, p < 0.05), and increased arterial PaO2 (53+/-14 mm Hg, control versus 174+/-71 mm Hg, BQ 123, p < 0.05) 8 h after the onset of ventilation. We conclude that circulating levels of ET-1 increase after delivery of premature lambs with severe HMD, and that selective ET(A) receptor blockade causes sustained improvement in hemodynamics in severe experimental HMD. These studies suggest that ET-1 contributes to the hemodynamic abnormalities in this model of pulmonary hypertension and severe HMD.
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PMID:Endothelin A receptor blockade decreases pulmonary vascular resistance in premature lambs with hyaline membrane disease. 970 10

Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV). Accordingly, intravenously applied ET(A) receptor antagonists reduce HPV, but this is accompanied by systemic vasodilation. We hypothesized that inhalation of an ET(A) receptor antagonist might act selectively on the pulmonary vasculature and investigated the effects of aerosolized LU-135252 in an experimental model of HPV. Sixteen piglets (weight: 25 +/- 1 kg) were anesthetized and mechanically ventilated at an inspiratory oxygen fraction (Fi(O(2))) of 0.3. After 1 h of hypoxia at Fi(O(2)) 0.15, animals were randomly assigned either to receive aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to receive aerosolized saline (n = 8, controls). In all animals, hypoxia significantly increased mean pulmonary arterial pressure (32 +/- 1 vs. 23 +/- 1 mmHg; P < 0.01; means +/- SE) and increased arterial plasma ET-1 (0.52 +/- 0.04 vs. 0.37 +/- 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at Fi(O(2)) 0.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean pulmonary arterial pressure compared with controls (LU group: 27 +/- 1 mmHg; controls: 32 +/- 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean systemic arterial pressure and cardiac output remained stable and were not significantly different from control values. Consequently, in our experimental model of HPV, the inhaled ET(A) receptor antagonist LU-135252 induced selective pulmonary vasodilation without adverse systemic hemodynamic effects.
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PMID:Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. 1807 16

We examined the hypothesis that persistent pulmonary hypertension of the newborn (PPHN) associated with ibuprofen is due to alterations in biochemical and molecular regulators of oxidative stress and NO signaling. Newborn rats breathing 50% O2 or room air from the first day of life (P1), received early IP injections of: 1) indomethacin (0.2 mg/kg) on P1 and 0.1 mg/kg on P2 and P3; 2) ibuprofen (10 mg/kg) on P1 and 5 mg/kg on P2 and P3; or 3) saline on P1, P2 and P3, then euthanized on P4; or late treatment on P4, P5 and P6, then euthanized on P7. Lung biomarkers for oxidative stress (8- epi-PGF2a), DNA damage (8-hydroxy-2'-deoxyguanosine) and pulmonary hypertension (ET-1, big ET-1, and total NO) were assessed. Despite timing of the dose and oxygen exposure, both drugs resulted in increased alveolar size. Both drugs had no beneficial effects on oxidative stress. Indomethacin treatment in O2 resulted in higher pulmonary levels of 8-epi-PGF2alpha which was associated with downregulation of most antioxidant genes with early treatment and overexpression of GPX5 and 6 with late treatment. Early and late ibuprofen treatment suppressed hyperoxia-induced NOx production and downregulated iNOS. Postponing treatment had no significant beneficial effects on biomolecular regulators of oxidative stress and NO signaling. The effect of ibuprofen on pulmonary NOx may explain in part, the transient PPHN seen in ibuprofen-treated preterm infants.
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PMID:Effects of combined hyperoxia and cyclooxygenase inhibition in neonatal rat lungs. 2058 71

Challenges in the evaluation of the retinal microstructure. To facilitate evaluation of the retinal microstructure we participated in the development of a scanning laser ophthalmoscope (SLO) for 32 years. The 'retro-mode' is the latest developed lateral aperture SLO made in Japan. This instrument enables us to observe the cystoid spaces and retinal microfolds underlying the epiretinal membrane. We investigated the pathogenesis and the mechanism of early development of idiopathic macular holes (MHs) and the vitreomacular interface in idiopathic full-thickness MHs using spectral-domain optical coherence tomography (SD-OCT). We studied the anatomic morphology of stage 1-A impending MHs, characterized by a foveolar yellow spot, using SD-OCT in the fellow eyes of patients diagnosed with a full-thickness MH. SD-OCT showed the reflectivity of the perifoveal posterior vitreous detachment (PVD) with vitreofoveal adhesion in the eyes with a yellow spot; the foveal microstructure had a triangular foveolar detachment of the cone outer segment tip line. The foveolar detachment of the cone outer segment tip line might be responsible for the yellow spot seen in stage 1-A MHs. Using SD-OCT, we also analyzed the vitreomacular interface in idiopathic full-thickness MHs and identified four configurations of the vitreomacular interface in MHs without a complete PVD. The majority, i.e., 92%, of eyes with a MH without a complete PVD are likely due to the anteroposterior vitreofoveal traction exerted by a perifoveal PVD. About 55% of cases with an open roof in the eyes without a complete PVD might be at risk of progression to operculum formation (loss of retinal tissue). 2. Challenges in the evaluation of retinal function SLO microperimetry is used to evaluate the retinal function during observation of the retinal microstructure. We evaluated the retinal sensitivity and the focal visual acuity using our original microperimetry program and clarified the characteristics of the preferred retinal locus (PRL) in macular diseases and the importance of the PRL evaluation. Further refinement of the SLO as an all-in-one instrument with the addition of a treatment feature is planned. We evaluated the retinal blood flow (RBF) using a laser Doppler velocimetry instrument that we developed. In clinical studies, we found that the RBF decreased in patients with type 2 diabetes mellitus with no or mild retinopathy compared with healthy subjects. In in vivo animal studies performed in anesthetized cats, we elucidated the mechanism of RBF regulation in response to physiologic stimuli, i.e., systemic hypoxia, hypercapnia, hyperoxia, hyperglycemia and hypertension. We showed that the retinal vascular endothelium plays an important role in regulating the RBF. In in vitro studies, we examined the effects of laminar shear stress on gene expression in human retinal microvascular endothelial cells (HRMECs) and found that long-term exposure to physiologic shear stress in the retinal arterioles upregulated eNOS and thrombomodulin mRNA expression and down-regulated ET-1 mRNA expression in the HRMECs. In ex vivo studies, we found that simvastatin, pioglitazone, resveratrol and fenofibrate dilated isolated porcine retinal arterioles, suggesting that systemic administration of these drugs may have the therapeutic potential to improve the impaired RBF in patients with type 2 diabetes mellitus. 3. Challenges to the development of a telemedicine support system We established a real-time telemedicine system that can transmit precise retinal images of patients between Asahikawa Medical University Hospital and our branch hospitals. We also developed a method of 3-dimensional high-definition transmission and stereoscopic display for ophthalmology. Moreover, we established a system to share medical information using Peer to Peer technology and network control technology that can transmit urgent information during a disaster. In response to a request from the Chinese Government, which has limited medical facilities in rural areas, we donated our system to four hospitals in Beijing, Shanghai, Sichuan and Shaanxi Provinces. As a result of the development of our unique telemedicine home medical care system, patients can be followed at home even after discharge from a hospital. 4. Conclusions. We believe that ophthalmologists can obtain important information about not only ocular but also systemic diseases by analyzing the retinal microstructure and functions simultaneously and can share this information worldwide via the telemedicine technology that we established, which can be a promising advance in patient care.
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PMID:[Noninvasive analysis of retinal microstructure and function: challenges and a promising future]. 2363 Dec 55