Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats

Am J Respir Crit Care Med. 2005 Oct 15;172(8):1002-7. doi: 10.1164/rccm.200501-005OC. Epub 2005 Aug 18.

Abstract

Rationale: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI.

Objectives: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation.

Methods: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein.

Results: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent.

Conclusions: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Capillary Permeability / drug effects
  • Cell Count
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Extravascular Lung Water / drug effects
  • Hydrochloric Acid / adverse effects
  • Infusions, Intravenous
  • Instillation, Drug
  • Isotonic Solutions / pharmacology
  • Isotonic Solutions / therapeutic use
  • Leukocyte Count
  • Male
  • Neutrophils
  • Osmolar Concentration
  • Plasma / drug effects
  • Pneumonia, Aspiration / chemically induced
  • Pneumonia, Aspiration / complications*
  • Proteins / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / diagnosis
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / prevention & control*
  • Ringer's Solution
  • Sucrose / pharmacology
  • Sucrose / therapeutic use*
  • Time Factors

Substances

  • Isotonic Solutions
  • Proteins
  • Sucrose
  • Ringer's Solution
  • Hydrochloric Acid