Effects of manganese superoxide dismutase nebulization on pulmonary function in an ovine model of acute lung injury

Marc O. Maybauer, Yuji Kikuchi, Martin Westphal, Dirk M. Maybauer, Kazuya Nishida, Lillian D. Traber, Beena B. Westphal-Varghese, Naoki Morita, Perenlei Enkhbaatar, David Herndon, Daniel L. Traber

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15 Scopus citations

Abstract

Smoke inhalation injury is a major cause of morbidity and mortality in thermally injured individuals. There is evidence of increased oxygen free radical activity, e.g., superoxide, in association with smoke inhalation injury. Because superoxide dismutase converts the reactive superoxide radical to peroxide, we hypothesized that nebulization of manganese superoxide dismutase (Mn-SOD) into the airway might attenuate pulmonary dysfunction secondary to smoke inhalation injury. The present study was designed as a prospective, controlled, and randomized laboratory experiment to determine the effects of aerosolized Mn-SOD on lung fluid balance, as indexed by changes in pulmonary microvascular permeability, lung lymph flow (QL), and gas exchange in an established and clinically relevant ovine model of smoke inhalation injury. Fifteen female Merino sheep were chronically instrumented with a femoral arterial, a Swan-Ganz, and a left atrial catheter. In addition, the right caudal mediastinal lymph node was cannulated to measure QL (mL·h-1). Pneumatic occluders were placed around the right pulmonary veins for the determination of the reflection coefficient (σ). After 7 days of recovery, sheep were randomly allocated to (a) an untreated control group (4 groups of 12 breaths of cotton smoke), (b) an injured group treated with nebulized Mn-SOD (5 mg/kg), and (c) an injured group that received only the vehicle (nebulized saline). Nebulization was performed 1 h and 12 h after smoke inhalation. Mn-SOD nebulization attenuated the increase in both filtration coefficient and σ and significantly decreased lung tissue conjugated dienes. However, there were no differences in QL, PaO 2/FiO2 ratio, and bloodless lung wet/dry weight ratio between groups. Although Mn-SOD nebulization attenuated the loss of protein, it failed to improve lung edema and pulmonary gas exchange, thereby limiting its clinical use.

Original languageEnglish (US)
Pages (from-to)138-143
Number of pages6
JournalShock
Volume23
Issue number2
DOIs
StatePublished - Feb 2005

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Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Airway
  • Sheep
  • Smoke inhalation injury
  • Superoxide dismutase

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Maybauer, M. O., Kikuchi, Y., Westphal, M., Maybauer, D. M., Nishida, K., Traber, L. D., Westphal-Varghese, B. B., Morita, N., Enkhbaatar, P., Herndon, D., & Traber, D. L. (2005). Effects of manganese superoxide dismutase nebulization on pulmonary function in an ovine model of acute lung injury. Shock, 23(2), 138-143. https://doi.org/10.1097/01.shk.0000150777.39484.b0