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1.
J Physiol ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37843154

RESUMO

The unique property of the pulmonary circulation to constrict in response to hypoxia, rather than dilate, brings advantages in both health and disease. Hypoxic pulmonary vasoconstriction (HPV) acts to optimise ventilation-perfusion matching - this is important clinically both in focal disease (such as pneumonia) and in one-lung ventilation during anaesthesia for thoracic surgery. However, during global hypoxia such as that encountered at high altitude, generalised pulmonary vasoconstriction can lead to pulmonary hypertension. There is now a growing body of evidence that links the hypoxia-inducible factor (HIF) pathway and pulmonary vascular tone - in both acute and chronic settings. Genetic and pharmacological alterations to all key components of this pathway (VHL - von Hippel-Lindau ubiquitin E3 ligase; PHD2 - prolyl hydroxylase domain protein 2; HIF1 and HIF2) have clear effects on the pulmonary circulation, particularly in hypoxia. Furthermore, knowledge of the molecular biology of the prolyl hydroxylase enzymes has led to an extensive and ongoing body of research into the importance of iron in both HPV and pulmonary hypertension. This review will explore these relationships in more detail and discuss future avenues of research.

4.
Br J Anaesth ; 126(6): e195-e197, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836851
5.
J Appl Physiol (1985) ; 116(7): 885-92, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24030664

RESUMO

The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body.


Assuntos
Corpo Carotídeo/patologia , Hipóxia/genética , Pulmão/fisiopatologia , Mutação , Ventilação Pulmonar , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Aclimatação , Altitude , Animais , Corpo Carotídeo/metabolismo , Corpo Carotídeo/fisiopatologia , Modelos Animais de Doenças , Genótipo , Hiperplasia , Hipertrofia , Hipóxia/metabolismo , Hipóxia/patologia , Hipóxia/fisiopatologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Fenótipo , Fatores de Tempo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
6.
High Alt Med Biol ; 13(3): 185-92, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22994518

RESUMO

OBJECTIVE: Recent studies have investigated visual analogue scales (VAS) as an alternative to the Lake Louise AMS Self-Report Score (LLS) for the self-assessment of acute mountain sickness (AMS). We investigated their use in adolescents. METHODS: The study was conducted during the 2009 and 2010 British Schools Exploring Society 35-day expeditions to Ladakh. Comparable ascent profiles were followed, reaching a maximum altitude of 6000 m. LLS and VAS AMS scores were recorded each morning. VAS comprised 100 mm lines for each LLS symptom; VAS scores were summed to give a composite daily total (VAS(c), expressed as a percentage). In 2010, an additional line was used to score overall "altitude sickness' (VAS(o)). RESULTS: 42 individuals participated in 2009 (83% compliance; mean age 17.4 years); 28 in 2010 (82% compliance; 17.5 years). 759 data points were recorded in 2009; 529 in 2010. There was a significant correlation between LLS and VAS(c) on both expeditions (rho=0.80, p<0.001 in 2009; rho=0.65, p<0.001 in 2010). These significant correlations remained when cases of AMS were analyzed separately. However, in all cases, the relationship between LLS and VAS was distorted, with a tendency for VAS to underscore symptoms of AMS when LLS<5. A VAS(c) value of 5.5% had an 82% specificity and sensitivity for all cases of AMS; VAS(c) of 9.5% had a 90% specificity and sensitivity for moderate and severe AMS. CONCLUSIONS: Whilst adolescents are capable of self-monitoring for AMS using VAS, the relationship with LLS is distorted. The LLS, despite its limitations, therefore remains the preferred method for the self-assessment of AMS in adolescents.


Assuntos
Doença da Altitude/diagnóstico , Autoavaliação Diagnóstica , Expedições , Índice de Gravidade de Doença , Adolescente , Adulto , Altitude , Doença da Altitude/complicações , Doença da Altitude/fisiopatologia , Área Sob a Curva , Tontura/etiologia , Fadiga/etiologia , Feminino , Cefaleia/etiologia , Humanos , Índia , Masculino , Montanhismo , Náusea/etiologia , Medição da Dor , Curva ROC , Inquéritos e Questionários , Vômito/etiologia , Adulto Jovem
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