GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance.

Abstract

INTRODUCTION:

Mechanical ventilators are increasingly used in critical care units. However, they can cause lung injury, including pulmonary edema. Our previous studies indicated that γ-aminobutyric acid (GABA) receptors are involved in alveolar-fluid homeostasis. The present study investigated the role of GABA receptors in ventilator-induced lung injury.

METHODS:

Adult female Sprague-Dawley rats were subjected to high-tidal-volume ventilation of 40 ml/kg body weight for 1 hour, and lung injuries were assessed.

RESULTS:

High-tidal-volume ventilation resulted in lung injury, as indicated by an increase in total protein in bronchoalveolar fluid, wet-to-dry ratio (indication of pulmonary edema), and Evans Blue dye extravasation (indication of vascular damage). Intratracheal administration of GABA before ventilation significantly reduced the wet-to-dry ratio. Further, histopathologic analysis indicated that GABA reduced ventilator-induced lung injury and apoptosis. GABA-mediated reduction was effectively blocked by the GABAA-receptor antagonist, bicuculline. The GABA-mediated effect was not due to the vascular damage, because no differences in Evans Blue dye extravasation were noted. However, the decrease in alveolar fluid clearance by high-tidal-volume ventilation was partly prevented by GABA, which was blocked by bicuculline.

CONCLUSIONS:

These results suggest that GABA reduces pulmonary edema induced by high-tidal-volume ventilation via its effects on alveolar fluid clearance and apoptosis.

• Authors: Narendranath Reddy Chintagari, Lin Liu
• Journal: Critical care (London, England) (Crit Care) Vol. 16 Issue 2 Pg. R55 (Dec 12 2012) ISSN: 1466-609X [Electronic] England
• PMID: 22480160 (Publication Type: Journal Article)

Chemical References

• Receptors, GABA
• Evans Blue
• Bicuculline

Topics

• Animals
• Apoptosis
• Bicuculline (pharmacology)
• Bronchoalveolar Lavage Fluid
• Evans Blue
• Extravasation of Diagnostic and Therapeutic Materials
• Female
• In Situ Nick-End Labeling
• Pulmonary Edema (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, GABA (metabolism)
• Tidal Volume
• Ventilator-Induced Lung Injury (metabolism)
• Ventilators, Mechanical (adverse effects)