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Critical Care
Published in: Critical Care 4/2008

Open Access 01-08-2008 | Research

High-molecular-weight hyaluronan – a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats

Authors: Yung-Yang Liu, Cheng-Hung Lee, Rejmon Dedaj, Hang Zhao, Hicham Mrabat, Aviva Sheidlin, Olga Syrkina, Pei-Ming Huang, Hari G Garg, Charles A Hales, Deborah A Quinn

Published in: Critical Care | Issue 4/2008

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Abstract

Introduction

Mechanical ventilation with even moderate-sized tidal volumes synergistically increases lung injury in sepsis and has been associated with proinflammatory low-molecular-weight hyaluronan production. High-molecular-weight hyaluronan (HMW HA), in contrast, has been found to be anti-inflammatory. We hypothesized that HMW HA would inhibit lung injury associated with sepsis and mechanical ventilation.

Methods

Sprague–Dawley rats were randomly divided into four groups: nonventilated control rats; mechanical ventilation plus lipopolysaccharide (LPS) infusion as a model of sepsis; mechanical ventilation plus LPS with HMW HA (1,600 kDa) pretreatment; and mechanical ventilation plus LPS with low-molecular-weight hyaluronan (35 kDa) pretreatment. Rats were mechanically ventilated with low (7 ml/kg) tidal volumes. LPS (1 or 3 mg/kg) or normal saline was infused 1 hour prior to mechanical ventilation. Animals received HMW HA or low-molecular-weight hyaluronan via the intraperitoneal route 18 hours prior to the study or received HMW HA (0.025%, 0.05% or 0.1%) intravenously 1 hour after injection of LPS. After 4 hours of ventilation, animals were sacrificed and the lung neutrophil and monocyte infiltration, the cytokine production, and the lung pathology score were measured.

Results

LPS induced lung neutrophil infiltration, macrophage inflammatory protein-2 and TNFα mRNA and protein, which were decreased in the presence of both 1,600 kDa and 35 kDa hyaluronan pretreatment. Only 1,600 kDa hyaluronan completely blocked both monocyte and neutrophil infiltration and decreased the lung injury. When infused intravenously 1 hour after LPS, 1,600 kDa hyaluronan inhibited lung neutrophil infiltration, macrophage inflammatory protein-2 mRNA expression and lung injury in a dose-dependent manner. The beneficial effects of hyaluronan were partially dependent on the positive charge of the compound.

Conclusions

HMW HA may prove to be an effective treatment strategy for sepsis-induced lung injury with mechanical ventilation.
Appendix
Available only for authorised users
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Metadata
Title
High-molecular-weight hyaluronan – a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats
Authors
Yung-Yang Liu
Cheng-Hung Lee
Rejmon Dedaj
Hang Zhao
Hicham Mrabat
Aviva Sheidlin
Olga Syrkina
Pei-Ming Huang
Hari G Garg
Charles A Hales
Deborah A Quinn
Publication date
01-08-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc6982

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