Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury

Matthias Lange, Atsumori Hamahata, Perenlei Enkhbaatar, Robert A. Cox, Yoshimitsu Nakano, Martin Westphal, Lillian D. Traber, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Different isoforms of nitric oxide (NO) synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal NO synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured and untreated group (n = 6), or an injured group treated with simultaneous infusion of selective inducible and neuronal NO synthase inhibitors (n = 5). The injury was induced by 48 breaths of cotton smoke and a third-degree burn of 40% total body surface area. All sheep were mechanically ventilated and fluid resuscitated. The injury induced severe pulmonary dysfunction as indicated by decreases in PaO2/FiO2 ratio and increases in pulmonary shunt fraction, ventilatory pressures, lung lymph flow, and lung wet/dry weight ratio. The treatment fully prevented the elevations in lymph and plasma nitrate/nitrite levels, pulmonary shunting, ventilatory pressures, lung lymph flow, and wet/dry weight ratio and significantly attenuated the decline in PaO2/FiO2 ratio. In conclusion, simultaneous blockade of inducible and neuronal NO synthase exerts beneficial pulmonary effects in an ovine model of acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury. This novel treatment strategy may represent a useful therapeutic adjunct for patients with these injuries.

Original languageEnglish (US)
Pages (from-to)626-631
Number of pages6
JournalShock
Volume35
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Inhalation Burns
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Sheep
Lung
Wounds and Injuries
Lymph
Smoke Inhalation Injury
Adult Respiratory Distress Syndrome
Pressure
Weights and Measures
Acute Lung Injury
Body Surface Area
Pulmonary Edema
Nitrites
Nitric Oxide Synthase
Smoke
Nitrates
Protein Isoforms
Therapeutics

Keywords

  • Acute lung injury
  • microvascular hyperpermeability
  • nitric oxide
  • sheep

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury. / Lange, Matthias; Hamahata, Atsumori; Enkhbaatar, Perenlei; Cox, Robert A.; Nakano, Yoshimitsu; Westphal, Martin; Traber, Lillian D.; Herndon, David; Traber, Daniel L.

In: Shock, Vol. 35, No. 6, 06.2011, p. 626-631.

Research output: Contribution to journalArticle

Lange, M, Hamahata, A, Enkhbaatar, P, Cox, RA, Nakano, Y, Westphal, M, Traber, LD, Herndon, D & Traber, DL 2011, 'Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury', Shock, vol. 35, no. 6, pp. 626-631. https://doi.org/10.1097/SHK.0b013e31820fe671
Lange, Matthias ; Hamahata, Atsumori ; Enkhbaatar, Perenlei ; Cox, Robert A. ; Nakano, Yoshimitsu ; Westphal, Martin ; Traber, Lillian D. ; Herndon, David ; Traber, Daniel L. / Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury. In: Shock. 2011 ; Vol. 35, No. 6. pp. 626-631.
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