Unfractionated heparin and enoxaparin reduce high-stretch ventilation augmented lung injury: a prospective, controlled animal experimentReportar como inadecuado

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Critical Care

, 13:R108

First Online: 06 July 2009Received: 13 March 2009Accepted: 06 July 2009


IntroductionDysregulation of coagulation and local fibrinolysis found in patients with acute lung injury often results in the need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and suppression of fibrinolytic activity, but the mechanisms are unclear. We hypothesized that subcutaneous injections of unfractionated heparin and enoxaparin would decrease neutrophil infiltration, lung edema, and plasminogen-activator inhibitor-1 PAI-1 production in mice exposed to high-tidal-volume ventilation.

MethodsMale C57BL-6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume 30 ml-kg or low-tidal-volume 6 ml-kg mechanical ventilation with room air for 1 to 5 hours after 200 IU-kg or 400 IU-kg unfractionated heparin and 4 mg-kg or 8 mg-kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet- to dry-weight ratio, histopathologic grading of epithelium, myeloperoxidase, and gene expression of PAI-1 were measured. The expression of PAI-1 was studied by immunohistochemistry.

ResultsHigh-tidal-volume ventilation induced increased microvascular permeability, neutrophil influx, PAI-1 mRNA expression, production of PAI-1 protein, and positive staining of PAI-1 in epithelium in a dose-dependent manner. Lung injury induced by high-tidal-volume ventilation was attenuated with PAI-1-deficient mice and pharmacologic inhibition of PAI-1 activity by low-dose unfractionated heparin and enoxaparin.

ConclusionsWe conclude that high-tidal-volume mechanical ventilation increased microvascular permeability, neutrophil influx, lung PAI-1 mRNA expression, production of active PAI-1. The deleterious effects were attenuated by low-dose unfractionated heparin or enoxaparin treatment. Understanding the protective mechanism of unfractionated heparin and enoxaparin related to the reduction of PAI-1 may afford further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury.

AbbreviationsALIacute lung injury

ARDSacute respiratory distress syndrome

BALbronchoalveolar fluid


EBDEvans blue dye

ESembryonic stem cells

GAPDHglyceraldehyde-phosphate dehydrogenase

HandEhematoxylin and eosin



LMWHlow-molecular-weight heparin

MIP-2macrophage inflammatory protein-2


PaCO2arterial carbon dioxide pressure

PaO2arterial oxygen pressure

PAFplatelet-activating factor

PAI-1plasminogen activator inhibitor-1

RT-PCRreverse transcription-polymerase chain reaction

TGF-β1transforming growth factor-β1

TMB3,3-, 5,5-tetramethylbenzidine

TNF-αtumor necrosis factor-alpha

tPAtissue-type plasminogen activator

uPAurokinase-type plasminogen activator

VILIventilator-induced lung injury

VTtidal volume.

Electronic supplementary materialThe online version of this article doi:10.1186-cc7949 contains supplementary material, which is available to authorized users.

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Autor: Li-Fu Li - Chung-Chi Huang - Horng-Chyuan Lin - Ying-Huang Tsai - Deborah A Quinn - Shuen-Kuei Liao

Fuente: https://link.springer.com/

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