Heparin Nebulization Attenuates Acute Lung Injury in Sepsis Following Smoke Inhalation in Sheep

Abstract

Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. We hypothesized that nebulized heparin could be an effective means of reducing cast formation. Female sheep (n = 19) were surgically prepared for a study of acute lung injury (ALI). After a tracheotomy, 48 breaths of cotton smoke (<40 degrees C) were inflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x 10(11) CFU) was instilled into the lung. All sheep were mechanically ventilated with 100% O2 and were divided into four groups: a heparin-nebulized group (n = 5; animals received aerosolized heparin [10,000 I.U.] 1 h after the bacterial instillation and subsequently every 4 h thereafter), an intravenous heparin group (n = 5,300 U/kg/23 h, infusion was started 1 h after the injury), a saline-nebulization group (n = 5; animals received inhaled nebulized saline), and a sham injury group (n = 4, treated in the same fashion, but no injury). The animals were sacrificed after 24 h of mechanical ventilation, and lung samples were harvested. Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes and a corresponding drop in PaO2. These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI.

Calcitonin Gene-Related Peptide Ameliorates Hyperoxia-Induced Lung Injury in Neonatal Rats

“…Under light microscopy, magnified digital images were captured using an Olympus BX40 microscope (Olympus Optical, Tokyo, Japan). The Murakami technique, which helps in histological assessment of features, such as edema, congestion, hemorrhage, infiltration of inflammatory cells, and cell proliferation, was employed to grade the degree of lung tissue injury (Murakami et al 2002). Each of these features was graded according to the following scale: 0, absent and appears normal; 1, light or nonsignificant damage; 2, moderate damage; 3, strong damage that may interfere with function; and 4, intense damage that may highly impair or eliminate function.…”

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…However, regulatory agencies and cost may limit the number of animals employed in these studies, which in turn may influence the statistical analysis of the results. The dog model has been utilized to study the delivery of insulin [65] or the treatment of some allergies [66]; monkeys and non-human primates have been employed to assess vaccine delivery [67] or drugs to treat cystic fibrosis [68], where sheep are considered a good model of lung injury [69].…”

Nebulized anticoagulants in lung injury in critically ill patients—an updated systematic review of preclinical and clinical studies

“…An effect of nebulized heparin on systemic coagulation was reported in one study using a lung injury model (49), but not in studies using pulmonary infection models (36,49) or inhalation trauma models (38)(39)(40)(41)(42). None of these studies, however, showed systemic bleeding.…”

“…Nebulized heparin also affected various physiologic parameters and other outcomes, in particular during pulmonary infection (34,35), and inhalation trauma (38)(39)(40)(41)(42)). An effect of nebulized heparin on systemic coagulation was reported in one study using a lung injury model (49), but not in studies using pulmonary infection models (36,49) or inhalation trauma models (38)(39)(40)(41)(42).…”