ABSTRACT
Recent studies demonstrate that sustained hypoxia induces the robust accumulation of leukocytes and mesenchymal progenitor cells in pulmonary arteries (PAs). Since the factors orchestrating hypoxia-induced vascular inflammation are not well-defined, the goal of this study was to identify mediators potentially responsible for recruitment to and retention and differentiation of circulating cells within the hypoxic PA. We analyzed mRNA expression of 44 different chemokine/chemokine receptor, cytokine, adhesion, and growth and differentiation genes in PAs obtained via laser capture microdissection in adjacent lung parenchyma and in systemic arteries by RT-PCR at several time points of hypoxic exposure (1, 7, and 28 days) in Wistar-Kyoto rats. Analysis of inflammatory cell accumulation and protein expression of selected genes was concomitantly assessed by immunochemistry. We found that hypoxia induced progressive accumulation of monocytes and dendritic cells in the vessel wall with few T cells and no B cells or neutrophils. Upregulation of stromal cell-derived factor-1 (SDF-1), VEGF, growth-related oncogene protein-alpha (GRO-alpha), C5, ICAM-1, osteopontin (OPN), and transforming growth factor-beta (TGF-beta) preceded mononuclear cell influx. With time, a more complex pattern of gene expression developed with persistent upregulation of adhesion molecules (ICAM-1, VCAM-1, and OPN) and monocyte/fibrocyte growth and differentiation factors (TGF-beta, endothelin-1, and 5-lipoxygenase). On return to normoxia, expression of many genes (including SDF-1, monocyte chemoattractant protein-1, C5, ICAM-1, and TGF-beta) rapidly returned to control levels, changes that preceded the disappearance of monocytes and reversal of vascular remodeling. In conclusion, sustained hypoxia leads to the development of a complex, PA-specific, proinflammatory microenvironment capable of promoting recruitment, retention, and differentiation of circulating monocytic cell populations that contribute to vascular remodeling.
Subject(s)
Hypertension, Pulmonary/immunology , Hypoxia/immunology , Pneumonia/immunology , Pulmonary Artery/immunology , Pulmonary Circulation/immunology , Animals , Aorta, Thoracic/physiology , Cell Adhesion Molecules/genetics , Chemokines/genetics , Chronic Disease , Cytokines/genetics , Dendritic Cells/immunology , Dendritic Cells/pathology , Gene Expression Regulation/immunology , Intercellular Signaling Peptides and Proteins/genetics , Lung/blood supply , Lung/physiology , Monocytes/immunology , Monocytes/pathology , Oligonucleotide Array Sequence Analysis , Pneumonia/pathology , Pulmonary Artery/pathology , Rats , Rats, Inbred WKY , Receptors, Chemokine/geneticsABSTRACT
OBJECTIVES: To review the current therapeutic approach of intracranial hypertension in pediatric patients admitted to intensive care unit. SOURCES OF DATA: Bibliographic review of the subject based on Medline. SUMMARY OF THE FINDINGS: The authors noticed that some measures to control intracranial hypertension are consensual, and others remain controversial. CONCLUSION: The goals of management of pediatric patients with intracranial hypertension include: normalizing the intracranial pressure, optimizing cerebral blood flow and cerebral perfusion pressure, preventing second insults that exacerbate secondary injury, and avoiding complications associated with the various treatment modalities employed.
Subject(s)
Intracranial Hypertension/therapy , Child , Glasgow Coma Scale , Humans , Intensive Care Units, Pediatric , Intracranial Hypertension/diagnostic imaging , Monitoring, Physiologic , Tomography, X-Ray ComputedABSTRACT
OBJETIVO: revisar a abordagem terapêutica atual nos pacientes pediátricos com hipertensäo intracraniana, internados em unidade de terapia intensiva. FONTE DE DADOS: revisäo bibliográfica sobre o tema, utilizando como base de dados o Medline. SíNTESE DOS DADOS: a partir da literatura levantada pode-se observar a existência de medidas de monitorizaçäo e tratamento da hipertensäo intracraniana aceitas como consenso pelos diferentes autores, assim como abordagens que ainda motivam controvérsias. CONCLUSÕES: os objetivos no manejo do paciente pediátrico com hipertensäo intracraniana incluem a normalizaçäo da pressäo intracraniana, a otimizaçäo do fluxo sangüíneo cerebral e pressäo de perfusäo cerebral, prevenindo o segundo insulto que exacerba a lesäo secundária, evitando as complicações associadas com as várias modalidades de tratamento empregadas.
