Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep

Katsumi Shimoda, Kazunori Murakami, Perenlei Enkhbaatar, Lillian D. Traber, Robert A. Cox, Hal K. Hawkins, Frank C. Schmalstieg, Katalin Komjáti, Jon G. Mabley, Csaba Szabó, Andrew L. Salzman, Daniel L. Traber

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91 Scopus citations

Abstract

We investigated the role of the nuclear enzyme poly (ADP ribose) synthetase (PARS) in the pathogenesis of combined burn and smoke inhalation (burn/smoke) injury in an ovine model. Eighteen sheep were operatively prepared for chronic study. PARS inhibition was achieved by treatment with a novel and selective PARS inhibitor INO-1001. The PARS inhibitor attenuated 1) lung edema formation, 2) deterioration of gas exchange, 3) changes in airway blood flow, 4) changes in airway pressure, 5) lung histological injury, and 6) systemic vascular leakage. Lipid oxidation and plasma nitrite/nitrate (stable breakdown products of nitric oxide) levels were suppressed with the use of INO-1001. We conclude that PARS inhibition attenuates various aspects of the pathophysiological response in a clinically relevant experimental model of burn/smoke inhalation injury.

Original languageEnglish (US)
Pages (from-to)L240-L249
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number1 29-1
StatePublished - Jul 1 2003

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Keywords

  • Acute respiratory distress syndrome
  • Lung lymphatic
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Shimoda, K., Murakami, K., Enkhbaatar, P., Traber, L. D., Cox, R. A., Hawkins, H. K., Schmalstieg, F. C., Komjáti, K., Mabley, J. G., Szabó, C., Salzman, A. L., & Traber, D. L. (2003). Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. American Journal of Physiology - Lung Cellular and Molecular Physiology, 285(1 29-1), L240-L249.