thromboxane-a2 and Burns

This study has shown that multiple organ failure (MOF) is one of the major causes of death in patients with severe burns. Both the plasma and visceral levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio were significantly increased. The changed plasma levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio paralleled the deterioration of the general condition in MOF patients. The circulatory platelet aggregation ratios (CPAR) in the MOF patients initially declined then dropped profoundly at 5-7 days postburn, indicating more microaggregate formation. CPK, LDH and GOT had increased markedly by 1 day, were elevated further at 2-3 days, and remained at supranormal levels for the first 7 days postburn. Degeneration, destruction, oedema, haemorrhage and thrombosis were observed in tissues from patients who died due to heart, lung, renal and hepatic failure. Clinically, 13 of the 16 MOF cases developed organ failure and 11 died between 3 and 7 days postburn. These findings confirmed that the increases of TXA2 and the TXA2/PGI2 ratio in plasma and visceral tissues can be an important factor in the genesis and development of postburn MOF.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Body Surface Area; Burns; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Shock; Thromboxane A2

Thromboxane (TXA2) and prostacyclin (PGI2) levels, circulatory platelet aggregate ratios (CPAR), CPK, LDH, GOT, platelet counts, blood viscosity, cortisol and urine epinephrine contents were determined in 42 burned patients who were divided into two groups: Group I control (n = 34) and Group II (n = 8) treated with TXA2 synthesis inhibitor, anisodamine. It was found that in controls, both TXA2 and the TXA2/PGI2 ratio increased significantly. There was no marked difference in PGI2 levels between the two groups. Platelet counts and CPAR decreased, while blood viscosity, CPK, LDH, GOT, cortisol and epinephrine in the controls were all significantly higher than those found in Group II patients. All these findings suggested that the changes of TXA2 and the TXA2/PGI2 ratios played an important role in the haemodynamics and haemorrheology in burn shock. The TXA2 synthesis inhibitor, anisodamine, showed beneficial effects by restoring the haemodynamic and rheological disturbances towards normal by virtue of their ability to induce vascular constriction, platelet aggregation, cellular destruction, destabilization of membranes and release of chemical mediators (including enzymes). Furthermore, at 1-3 days postburn, the levels of CPK, LDH and GOT in controls were higher than those measured at 12 h postburn, but this phenomenon was not marked in the treated group, suggesting that after resuscitation, reperfusion damage had occurred and TXA2 might be responsible for the damage. It is assumed that anisodamine could protect tissues from reperfusion damage. The findings also suggested that anisodamine could quicken the restoration of neuroendocrine disturbance initiated by shock (stress).

Topics: Adolescent; Adult; Aspartate Aminotransferases; Burns; Creatine Kinase; Epinephrine; Female; Humans; Hydrocortisone; Infusions, Intravenous; L-Lactate Dehydrogenase; Male; Middle Aged; Shock; Solanaceous Alkaloids; Thromboxane A2; Thromboxane B2; Vasodilator Agents

We injected Escherichia coli endotoxin, 2 micrograms/kg, beneath the eschar of sheep with 25% total body surface full-thickness burns to determine whether burn tissue in the presence of endotoxin releases prostanoids, particularly thromboxane A2, (TxA2), and if increased local TxA2 production can lead to distant lung dysfunction. We compared this response to the lung injury produced by the same dose given intravenously. We noted a marked increase in burn tissue TxA2 production after subeschar endotoxin as reflected in significant increases in burn lymph and pulmonary artery TxB2 levels. Pulmonary artery pressure increased from 22 to 38 mm Hg and PaO2 decreased from 89 to 71 torr while lung lymph flow (QL) increased only modestly with no evidence of increased lung permeability. The TxA2 production and the lung response were prevented by the subeschar injection of ibuprofen, 12.5 mg/kg. Circulating endotoxin was noted in only one of five sheep. After intravenous (endotoxin), a significant increase in lung TxA2 production was noted and a characteristic two-phase lung injury was seen with an initial phase basically identical to that seen with the subeschar injection followed by an increase in lung protein permeability. Burn tissue endotoxin can stimulate local TxA2 production leading to distant lung dysfunction without the need for circulating endotoxin. The source of the TxA2 is the burn, while with endotoxemia the source is the lung.

Topics: Animals; Burns; Endotoxins; Hemodynamics; Ibuprofen; Injections, Intravenous; Lung Diseases; Lymph; Pulmonary Artery; Sheep; Thromboxane A2; Thromboxanes; Time Factors

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

Topics: Animals; Burns; Endotoxins; Epoprostenol; Escherichia coli; Female; Hemodynamics; Hypertension, Pulmonary; Lung; Lymph; Oxygen; Partial Pressure; Sheep; Thromboxane A2; Thromboxane B2; Time Factors

Within 24 hours after a full-thickness burn injury, predictable alterations occur in the dermal vasculature. At the immediate site of injury, vessels lose patency. In the periphery, vasodilation and increased permeability become widespread. A variety of interventions were employed to prevent these vascular sequelae. While systemic treatment, immediately after burn trauma, with hydrocortisone or the non-steroidal anti-inflammatory compound indomethacin, was ineffective in preventing vascular alteration, treatments with other NSAI agents such as ibuprofen and imidazole were effective in preventing microvascular occlusion. In addition, utilizing standard radioimmunoassay techniques, the concentrations of the metabolites of two potent eicosanoids, thromboxane and prostacyclin, were measured from fluid collected in the implanted wound chambers. Following full-thickness burns, the synthesis and release of thromboxane were inhibited by indomethacin, imidazole, and ibuprofen. Furthermore, indomethacin and ibuprofen, but not imidazole, blocked the synthesis and release of prostacyclin into wound fluid. Significantly, ibuprofen was effective in preserving the dermal vasculature, even when administration was delayed as long as 6 hours after burn trauma. Pharmacologic actions not associated with the production of thromboxane or prostacyclin appear responsible for the protective effects of ibuprofen during burn injury. Such findings do not support an important role for either thromboxane or prostacyclin in the development of vascular alterations following burn injury.

Topics: Animals; Anti-Inflammatory Agents; Blood Coagulation; Burns; Epoprostenol; Hydrocortisone; Ibuprofen; Imidazoles; Ischemia; Male; Rats; Rats, Inbred Strains; Skin; Thromboxane A2; Time Factors; Vasodilation

Topics: Animals; Burns; Capillary Permeability; Dogs; Epoprostenol; Hypertension, Pulmonary; Infections; Microcirculation; Prostaglandin Antagonists; Prostaglandins; Pulmonary Circulation; Pulmonary Embolism; Pulmonary Valve Insufficiency; Sheep; Shock, Hemorrhagic; Thromboxane A2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Fistula; Hemodynamics; Lung Diseases; Lymphatic Diseases; Lymphatic System; Prostaglandins; Sheep; Thromboxane A2; Thromboxane B2; Thromboxanes