Intratracheal heparin improves plastic bronchitis due to sulfur mustard analog

Pediatr Pulmonol. 2015 Feb;50(2):118-26. doi: 10.1002/ppul.23043. Epub 2014 Apr 1.

Abstract

Background: Inhalation of sulfur mustard (SM) and SM analog, 2-chloroethyl ethyl sulfide (CEES), cause fibrinous cast formation that occludes the conducting airways, similar to children with Fontan physiology-induced plastic bronchitis. These airway casts cause significant mortality and morbidity, including hypoxemia and respiratory distress. Our hypothesis was that intratracheal heparin, a highly cost effective and easily preserved rescue therapy, could reverse morbidity and mortality induced by bronchial cast formation.

Methods: Sprague-Dawley rats were exposed to 7.5% CEES via nose-only aerosol inhalation to produce extensive cast formation and mortality. The rats were distributed into three groups: non-treated, phosphate-buffered saline (PBS)-treated, and heparin-treated groups. Morbidity was assessed with oxygen saturations and clinical distress. Blood and bronchoalveolar lavage fluid (BALF) were obtained for analysis, and lungs were fixed for airway microdissection to quantify the extent of airway cast formation.

Results: Heparin, given intratracheally, improved survival (100%) when compared to non-treated (75%) and PBS-treated (90%) controls. Heparin-treated rats also had improved oxygen saturations, clinical distress and airway cast scores. Heparin-treated rats had increased thrombin clotting times, factor Xa inhibition and activated partial thromboplastin times, indicating systemic absorption of heparin. There were also increased red blood cells (RBCs) in the BALF in 2/6 heparin-treated rats compared to PBS-treated control rats.

Conclusions: Intratracheal heparin 1 hr after CEES inhalation improved survival, oxygenation, airway obstruction, and clinical distress. There was systemic absorption of heparin in rats treated intratracheally. Some rats had increased RBCs in BALF, suggesting a potential for intrapulmonary bleeding if used chronically after SM inhalation.

Keywords: CEES; heparin; inhalation injury; plastic bronchitis; pulmonology; sulfur mustard.

MeSH terms

  • Animals
  • Blood Coagulation Tests
  • Bronchitis / drug therapy*
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemical Warfare Agents / toxicity*
  • Drug Administration Routes
  • Erythrocytes / metabolism
  • Fibrinolytic Agents / administration & dosage*
  • Heparin / administration & dosage*
  • Models, Animal
  • Mustard Gas / analogs & derivatives*
  • Mustard Gas / toxicity
  • Oxygen / blood
  • Rats, Sprague-Dawley
  • Trachea

Substances

  • Chemical Warfare Agents
  • Fibrinolytic Agents
  • 2-chloroethyl ethyl sulfide
  • Heparin
  • Oxygen
  • Mustard Gas