thromboxane-b2 and Contusions

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.. 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.. 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.. 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.. 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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Capillary Permeability; Contusions; Cyclooxygenase Inhibitors; Epoprostenol; Hemodynamics; Hydrocortisone; Hypoxia; Indomethacin; Inflammation Mediators; Leukocytes; Lung; Lung Injury; Positive-Pressure Respiration; Prostaglandins; Swine; Thromboxane B2

The pathophysiologic sequence leading to respiratory failure after chest trauma can be an inevitable consequence of the primary injury or a secondary, mediator-driven inflammatory process. To distinguish between these alternatives, a simple cross-transfusion experiment was performed. A captive bolt gun injured the chest of anesthetized pigs that were mechanically ventilated with FiO2 = .21, .50, or .50 plus indomethacin (5 mg/kg intravenous; 15 min before injury). Tube thoracostomy immediately followed. After 30 min, blood from these injured donors was transfused into three matched groups of naive recipients (n = 8, 6, and 4, respectively) for a 33% exchange transfusion. Two control groups received blood from uninjured donors with tube thoracostomies only (FiO2 = .21, n = 7; FiO2 = .50, n = 10). Within 15-30 min after transfusion, in recipients from injured donors versus controls, lung compliance was decreased 20%, stroke volume and cardiac output were decreased 50%, and pulmonary vascular resistance was increased >300% (all p < .05). These changes recovered to baseline within 60-90 min. The stable metabolite of thromboxane A2, thromboxane B2, increased >500% in plasma within 15 min and remained elevated for >120 min. All responses were similar at 21 % or 50% O2, which suggests that hypoxia per se is not a cause of mediator production. All responses were eliminated by indomethacin. By 24 h, histologic changes included atelectasis in 3/3 recipients from injured donors versus 0/3 recipients from uninjured donors. We conclude that 1) blunt chest trauma releases blood borne mediators, including prostanoids; 2) these mediators can cause secondary cardiopulmonary changes in naive recipients similar to those produced by chest trauma; 3) the progression to trauma-induced respiratory failure is multifactorial; 4) early pharmacologic intervention, rather than supportive care alone, may benefit some victims of severe chest trauma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Transfusion; Cerebrovascular Disorders; Contusions; Edema; Female; Hemodynamics; Indomethacin; Male; Oxygen Consumption; Pneumonia; Pulmonary Artery; Swine; Thoracic Injuries; Thromboxane B2; Vascular Resistance

In multiple trauma patients with lung contusion, pulmonary complications have been reported that were attributed to intramedullary stabilization of the femur. The reaming procedure of the medullary canal is thought to play a major role. We investigated whether different types of reamers might exert different amounts of fat mobilization into the vascular system and different degrees of pulmonary dysfunction. Adult female Merino sheep were submitted to hemorrhagic shock (2 h, 50 mm Hg) and a unilateral lung contusion; in addition, a lung lymph fistula was created. Pulmonary capillary permeability, central venous triglyceride levels, 11-dehydro-thromboxane B2 (dh-TXB2) levels, and pulmonary artery pressure were determined. After recovery, animals were randomly assigned to intramedullary femoral nailing using several types of reamers: group A, AO reamer (n = 8); group B, Biomet reamer (n = 7); group H, Howmedica reamer (n = 6); group C, controls, no reaming (n = 4). Intramedullary reaming caused a significant (p < 0.05) increase in pulmonary artery pressure in groups A and B; dh-TXB2 levels increased in all groups. Statistically significant (p < 0.05) pulmonary capillary permeability damage was measured in group A only. Intramedullary femoral nailing can cause transient pulmonary hemodynamic and mediator effects as well as increased pulmonary capillary permeability. In the present study, this effect was evident in group A reamer systems only, which may be due to reamer construction.

Topics: Animals; Bone Nails; Capillary Permeability; Contusions; Disease Models, Animal; Embolism, Fat; Equipment Design; Female; Femoral Fractures; Fracture Fixation, Intramedullary; Lung Injury; Multiple Trauma; Pulmonary Circulation; Pulmonary Embolism; Severity of Illness Index; Sheep; Shock, Hemorrhagic; Thromboxane B2; Triglycerides

The relationship between bleeding and bruising and the production of prostacyclin and thromboxane was assessed in children who were to have a tonsillectomy and/or an adenoidectomy. Eicosanoids in the blood oozing from the bleeding time incision were measured and correlated with the reported frequency of bruising and epistaxis. A striking association (P = .0003) between prostacyclin production and the frequency of bruising was found; children reporting bleeding at least biweekly had the highest prostacyclin synthesis. Successively lower levels of the prostacyclin metabolite, 6-keto-prostaglandin F1 alpha, were found in children reporting less frequent bruising. Prostacyclin production in bleeding time blood was also correlated inversely with systolic blood pressure and hemoglobin level, although neither of these variables could explain the association between prostacyclin production and bruising. There was no correlation between thromboxane formation, systolic blood pressure, hemoglobin level, age, or bleeding time and the frequency of bruising. The ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha was correlated inversely with the length of the bleeding time (P = .016). It is concluded that vascular prostacyclin production may have a role in bruising symptomatology. It is suggested that prostacyclin formed at the injured vessel surface collects within the first few seconds after injury inside the tissue space at the site of the bruise and, by influencing the formation of the platelet/fibrin plug and/or the leakage of blood from the vessels, plays a significant role in modifying the development of bruising.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Bleeding Time; Blood Cell Count; Child; Child, Preschool; Contusions; Epoprostenol; Humans; Sex Factors; Thromboxane B2; Thromboxanes