Prostanoids: early mediators in the secondary injury that develops after unilateral pulmonary contusion.

Abstract

BACKGROUND:

We have previously shown a sequence of events after unilateral pulmonary contusion that suggests the release of blood-borne prostanoid mediators and that culminates in refractory bilateral pulmonary failure.

PURPOSE:

To determine the role of platelet-derived thromboxane and endothelial-derived prostacyclin in the primary and secondary injury after unilateral blunt chest trauma, and to determine whether pretreatment with the cyclooxygenase inhibitor indomethacin alters the progression of secondary injury.

METHODS:

Anesthetized, ventilated (FIO2 = 0.50) pigs received a unilateral, blunt injury to the right thorax (n = 20) or sham injury (n = 5) and were monitored for 24 hours. Either indomethacin (5 mg/kg i.v.; n = 10) or its saline vehicle (n = 10) were administered 15 minutes before injury. Serial bronchoalveolar lavages of each lung were analyzed for protein and neutrophil (polymorphonuclear neutrophil (PMN)) content.

RESULTS:

Contusion caused profound hypoxemia; PaO2 partially recovered within 1 hour of injury to 50% of baseline. Thereafter, worsening hypoxemia required positive end-expiratory pressure. With indomethacin compared with vehicle, PaO2 was higher at any given level of positive end-expiratory pressure (p < 0.05). There was an early increase in serial bronchoalveolar lavage protein on the injured side (peak at 2 hours), with a delayed pulmonary capillary leak on the contralateral side (peak at 6 hours), which correlated with increasing PMN infiltration; this was reduced by 40 to 60% with indomethacin (p < 0.05). Thromboxane peaked within 1 hour after contusion at 800% baseline, then fell off rapidly. This peak preceded the maximal increase in permeability and was completely blocked by indomethacin. Prostacyclin slowly rose to 300% baseline by 3 hours and remained elevated; this change was blocked by indomethacin for 18 hours.

CONCLUSIONS:

Contusion of the right thorax induced a delayed pulmonary capillary leak in the left lung, which reflects a progressive secondary inflammatory response. Elevations in thromboxane and prostacyclin preceded progressive bilateral PMN infiltration. Indomethacin blocked thromboxane and prostacyclin and attenuated, but did not prevent, the progression to pulmonary failure. Overall, these data suggest that prostanoids are released soon after unilateral contusion and initiate an inflammatory response in both lungs that is sustained by PMN infiltration.

• Authors: K A Davis, T C Fabian, M A Croce, K G Proctor
• Journal: The Journal of trauma (J Trauma) Vol. 46 Issue 5 Pg. 824-31; discussion 831-2 (May 1999) ISSN: 0022-5282 [Print] United States
• PMID: 10338399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cyclooxygenase Inhibitors
• Inflammation Mediators
• Prostaglandins
• Thromboxane B2
• 6-Ketoprostaglandin F1 alpha
• Epoprostenol
• Hydrocortisone
• Indomethacin

Topics

• 6-Ketoprostaglandin F1 alpha (blood)
• Animals
• Bronchoalveolar Lavage Fluid (cytology)
• Capillary Permeability
• Contusions (blood, complications, physiopathology)
• Cyclooxygenase Inhibitors (pharmacology)
• Epoprostenol (blood, physiology)
• Hemodynamics
• Hydrocortisone (blood)
• Hypoxia (etiology, therapy)
• Indomethacin (pharmacology)
• Inflammation Mediators (physiology)
• Leukocytes (pathology)
• Lung (blood supply, pathology)
• Lung Injury
• Positive-Pressure Respiration
• Prostaglandins (physiology)
• Swine
• Thromboxane B2 (blood, physiology)