Massive cutaneous burn combined with smoke inhalation causes high mortality in fire victims. Cyclo-oxygenase (COX) and inducible nitric oxide (NO) synthase (iNOS) have been shown to be up-regulated in burn injury. Ketorolac, a non-steroidal, anti-inflammatory agent (NSAID), inhibits prostaglandin and thromboxane synthesis through inhibition of COX. NSAIDs have been shown to down-regulate iNOS. Thus we hypothesized that treatment with ketorolac would attenuate burn/smoke-related cardiopulmonary derangements. We conducted a fully controlled long-term laboratory investigation in an Intensive Care Unit setting. Eighteen female sheep were surgically prepared for chronic study. After a recovery period of 5 days, a tracheotomy was performed under ketamine/halothane anaesthesia. Sheep were given a 40% total body surface third-degree burn and insufflated with cotton smoke (48 breaths, <40 °C). Sheep were divided into three groups: sham (not injured and not treated; n=6), control (injured, but not treated; n=6) and treated (injured and administered ketorolac 60 mg/day; n=6). The sham group had stable cardiopulmonary and systemic haemodynamics. Control animals showed depressed cardiopulmonary function, decreased pulmonary gas exchange, increased pulmonary microvascular leakage and decreased left ventricle stroke work index with elevated left atrial pressure. Systemic vascular leak in control animals was evidenced by robust haemoconcentration (haematocrit and fluid net balance). Treatment with ketorolac prevented all of these morbidities. Post-treatment with ketorolac also resulted in significant inhibition of elevated plasma nitrite/nitrate levels in control animals. These results suggest that ketorolac may ameliorate cardiopulmonary morbidity, at least in part, by inhibiting excessive NO.
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November 2003
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Research Article|
November 01 2003
Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury
Perenlei ENKHBAATAR;
Perenlei ENKHBAATAR
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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Kazunori MURAKAMI;
Kazunori MURAKAMI
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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Katsumi SHIMODA;
Katsumi SHIMODA
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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John SALSBURY;
John SALSBURY
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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Robert COX;
Robert COX
†Department of Pathology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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Hal HAWKINS;
Hal HAWKINS
†Department of Pathology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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Lillian TRABER;
Lillian TRABER
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
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David HERNDON;
David HERNDON
‡Department of Surgery University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77550-0833, U.S.A.
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Daniel TRABER
*Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, U.S.A.
Correspondence: Professor D. L. Traber (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
May 16 2003
Revision Received:
July 09 2003
Accepted:
July 28 2003
Accepted Manuscript online:
July 28 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 105 (5): 621–628.
Article history
Received:
May 16 2003
Revision Received:
July 09 2003
Accepted:
July 28 2003
Accepted Manuscript online:
July 28 2003
Citation
Perenlei ENKHBAATAR, Kazunori MURAKAMI, Katsumi SHIMODA, John SALSBURY, Robert COX, Hal HAWKINS, Lillian TRABER, David HERNDON, Daniel TRABER; Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury. Clin Sci (Lond) 1 November 2003; 105 (5): 621–628. doi: https://doi.org/10.1042/CS20030180
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