Etiology of the pulmonary pathophysiology associated with inhalation injury

Herndon, David N.; Traber, Lillian D.; Linares, Hugo A.; Flynn, John C.; Niehaus, G. D.; Kramer, George C.; Traber, Daniel L.

doi:10.1016/0300-9572(86)90006-7

Cited by 63 publications

(21 citation statements)

References 18 publications

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“…The initial morphologic changes after smoke inhalation injury are focal (1,3,20), although we suspect that the toxic components in smoke are distributed to the lung in a more uniform manner. Thus, some mechanism must lead to the observed focal distribution of injury.…”

Section: Discussionmentioning

confidence: 96%

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Airway Obstruction in Sheep with Burn and Smoke Inhalation Injuries

Cox

Burke

Soejima

et al. 2003

Am J Respir Cell Mol Biol

131

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The goals of this study were (i) to compare the degree and (ii) temporal changes in airway obstruction in sheep with pulmonary injury induced by smoke inhalation and/or burn; (iii) to qualitatively assess the cellular and mucous content of obstructive material; and (iv) to statistically assess a possible relationship between the degree of airway obstruction and pulmonary dysfunction. Using masked histologic slides, we estimated the degree of luminal obstruction in all cross-sectioned airways. The mean degree of bronchial, bronchiolar, and terminal bronchiolar obstruction was significantly greater in animals with smoke injury alone or combined smoke inhalation and burn (S+B) injury, compared with animals with burn injury alone or uninjured animals (P < 0.05). In S+B animals, the degree of bronchial obstruction was maximal at 24 h, with a progressive decrease over 72 h. In contrast, the degree of bronchiolar obstruction increased over time. Qualitatively, bronchial casts were largely composed of mucus at early times after injury, whereas neutrophils were the principal component of bronchiolar obstructive material. Localization of specific mucin subtypes in S+B tissues suggests that increasing bronchiolar obstruction is derived, in part, from upper airway material. Multiple linear regression analysis of airway obstruction scores compared with PaO2/FIO2 values showed a correlation coefficient of r = 0.76, with bronchial and bronchiolar scores predictive of PaO2/FIO2, (P < 0.05). These results suggest that strategies to remove or decrease formation of upper airway obstructive material may reduce its deposition into small airways and parenchyma and may improve respiratory function in victims of smoke inhalation injury.

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Section: Discussionmentioning

confidence: 96%

“…Animals used in this study were female, range-bred adult sheep weighing approximately 40 kg. Preparation for chronic study, and protocols for smoke and burn injury, have been described previously (1,3,11). Briefly, the animals were surgically prepared for study under endotracheal halothane anesthesia.…”

Section: Methodsmentioning

confidence: 99%

Airway Obstruction in Sheep with Burn and Smoke Inhalation Injuries

Cox

Burke

Soejima

et al. 2003

Am J Respir Cell Mol Biol

131

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“…Previous studies have described in detail the protocols for S + B injury [3,20]. Briefly, smoke inhalation injury was induced by burning 40 g of cotton towelling in a modified bee smoker attached to a tracheostomy tube.…”

Section: Injury Protocolsmentioning

confidence: 99%

Effects of a dual endothelin-1 receptor antagonist on airway obstruction and acute lung injury in sheep following smoke inhalation and burn injury

et al. 2005

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Studies have suggested that ET-1 (endothelin-1) is associated with lung injury, airway inflammation and increased vascular permeability. In the present study we have tested the hypothesis that treatment with a dual ET-1 receptor antagonist will decrease airway obstruction and improve pulmonary function in sheep with combined S+B (smoke inhalation and burn) injury. Twelve sheep received S+B injury using the following protocol: six sheep were treated with tezosentan, an ETA and ETB receptor antagonist, and six sheep received an equivalent volume of vehicle. Physiological and morphological variables were assessed during the 48 h study period and at the end of the study. There was no statistically significant difference in the PaO2/FiO2 (partial pressure of O2 in arterial blood/fraction of O2 in the inspired gas) ratio of the tezosentan-treated animals compared with controls; however, lung lymph flow was significantly higher (P<0.05) in the treated animals. PVRI (pulmonary vascular resistance index) was significantly reduced (P<0.05) in the tezosentan-treated animals. Assessment of NOx (nitric oxide metabolite) levels in plasma and lymph showed significantly elevated (P<0.05) levels in the tezosentan-treated animals compared with levels in untreated sheep. The degree of bronchial obstruction was similar in both treated and control sheep; however, bronchiolar obstruction was reduced in sheep treated with tezosentan. Histopathologically, no difference in the degree of parenchymal injury was detected. In conclusion, administration of a dual ET-1 receptor antagonist prevented an increase in PVRI after injury and reduced the degree of bronchiolar obstruction in sheep with S+B; however, treated sheep showed higher levels of NOx and increased lung lymph flow. Tezosentan treatment was ineffective in protecting against acute lung injury in this model.

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“…Thus ketorolac may attenuate ALI in this model by inhibiting excessive NO. On the other hand, we [22] have also reported a marked increase in airway levels of thromboxane after smoke inhalation. The action of the COX inhibitor may have more than one mechanism, for example, a reduction in NO production and a reduction in thromboxane.…”

Section: Figure 5 Effect Of Ketorolac On CI (A) and Lvswi (B)mentioning

confidence: 83%

Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury

et al. 2003

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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 degrees 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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Etiology of the pulmonary pathophysiology associated with inhalation injury

Cited by 63 publications

References 18 publications

Airway Obstruction in Sheep with Burn and Smoke Inhalation Injuries

Airway Obstruction in Sheep with Burn and Smoke Inhalation Injuries

Effects of a dual endothelin-1 receptor antagonist on airway obstruction and acute lung injury in sheep following smoke inhalation and burn injury

Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury

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