Isoflurane Ameliorates Acute Lung Injury by Preserving Epithelial Tight Junction Integrity.

BACKGROUND: Isoflurane may be protective in preclinical models of lung injury, but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. The authors hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. METHODS: Wild-type mice were treated with isoflurane 1 h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24 h before mechanical ventilation (MV; tidal volume, 15 ml/kg, 2 h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1 h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. RESULTS: Mice treated with isoflurane following exposure to inhaled endotoxin and before MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice after treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e., zona occludens 1) that was rescued by isoflurane treatment. CONCLUSIONS: Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension.

Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2-derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I2 analog abrogated monocrotaline-induced PA stiffening and attenuated stiffness-dependent increases in proliferation, matrix deposition, and contraction in PASMC. Our results suggest a pivotal role for early PA stiffening in PH and demonstrate the therapeutic potential of interrupting mechanobiological feedback amplification of vascular remodeling in experimental PH.

Enfoque práctico del síndrome metabólico en pediatría: [revisión] / Practical approach to metabolic syndrome in pediatrics: [review]

El síndrome metabólico en pediatría identifica a un grupo de niños con alto riesgo de presentar eventos cardiocerebrovascular y de diabetes tipo 2 a partir de los seis años de edad. La detección temprana y tratamiento óptimo constituyen el pilar fundamental para disminuir la morbimortalidad cardiovascular a mediano y largo plazo. Esta terapéutica creará hábitos saludables familiares y promoverá el control de los factores de riesgo como alteraciones metabólicas, hipertensión arterial y obesidad en cada integrante independiente de su edad. El presente artículo muestra un abordaje práctico en el ámbito clínico de los pacientes pediátricos a partir de los seis años...

The metabolic syndrome in pediatrics identify a high risk population for cardiocerebrovascular events and type 2 diabetes since six years old. Early detection and treatment of risk factors constitute the main point of intervention to decrease the morbidity and mortality related with cardiovascular disease in the medium and long terms. This treatment will create healthy family habits and it will promote the control of these risk factors in each family member. This article presents a practical approach on this issue in pediatric clinical care since six years of age...