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

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

Research output: Contribution to journal › Article › peer-review

100 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 language	English (US)
Pages (from-to)	L240-L249
Journal	American Journal of Physiology - Lung Cellular and Molecular Physiology
Volume	285
Issue number	1 29-1
State	Published - Jul 1 2003

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.

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

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.",

keywords = "Acute respiratory distress syndrome, Lung lymphatic, Nitric oxide",

author = "Katsumi Shimoda and Kazunori Murakami and Perenlei Enkhbaatar and Traber, {Lillian D.} and Cox, {Robert A.} and Hawkins, {Hal K.} and Schmalstieg, {Frank C.} and Katalin Komj{\'a}ti and Mabley, {Jon G.} and Csaba Szab{\'o} and Salzman, {Andrew L.} and Traber, {Daniel L.}",

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AU - Shimoda, Katsumi

AU - Murakami, Kazunori

AU - Enkhbaatar, Perenlei

AU - Traber, Lillian D.

AU - Cox, Robert A.

AU - Hawkins, Hal K.

AU - Schmalstieg, Frank C.

AU - Komjáti, Katalin

AU - Mabley, Jon G.

AU - Szabó, Csaba

AU - Salzman, Andrew L.

AU - Traber, Daniel L.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

KW - Acute respiratory distress syndrome

KW - Lung lymphatic

KW - Nitric oxide

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IS - 1 29-1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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