Effect of poly (ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep
K Shimoda, K Murakami… - … of Physiology-Lung …, 2003 - journals.physiology.org
K Shimoda, K Murakami, P Enkhbaatar, LD Traber, RA Cox, HK Hawkins, FC Schmalstieg…
American Journal of Physiology-Lung Cellular and Molecular …, 2003•journals.physiology.orgWe 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) …
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) …
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.
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