Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep.
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.
Shimoda
Katsumi
K
Department of Anesthesiology, The University of Texas Medical Branch, Shriners Burns Hospital, Galveston, Texas 77555-0833, USA.
Murakami
Kazunori
K
Enkhbaatar
Perenlei
P
Traber
Lillian D
LD
Cox
Robert A
RA
Hawkins
Hal K
HK
Schmalstieg
Frank C
FC
Komjati
Katalin
K
Mabley
Jon G
JG
Szabo
Csaba
C
Salzman
Andrew L
AL
Traber
Daniel L
DL
D000403:Airway Resistance; D000818:Animals; D001794:Blood Pressure; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D006400:Hematocrit; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008208:Lymphatic System / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011652:Pulmonary Circulation; D011659:Pulmonary Gas Exchange; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000378:metabolism; D014556:Urine
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase