thromboxane-b2 and Shock--Traumatic

A prospective study was carried out on 57 patients with total burned surface area (TBSA) over 30%. It was found that myocardial damage occurred early postburn, which was one of the major causes of cardiac dysfunction and failure. The postburn respiratory failure (RF) might be classified into three patterns. The etiology of each pattern varied. The imbalance between thromboxane and prostacyclin in plasma and visceral tissues played important roles in the genesis and development of postburn MOF as well as the causes of pathophysiological alterations in the main factors (including inhalation injury, severe shock and systemic infection) which contributed to occurrence of visceral damage and MOF.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Burns, Inhalation; Child; Female; Humans; Male; Multiple Organ Failure; Prospective Studies; Shock, Traumatic; Thromboxane B2

51 burned patients with TBSA over 30% were studied prospectively. MOF developed in 17 of them. Postburn MOF occurred mainly in those with TBSA over 70%. Mortality of MOF was directly proportional to the number of organs involved. The incidence of pulmonary failure was the highest, and the highest mortality was attributed to renal failure. MOF occurring in the early stage was more related to burn shock, and those occurring in the late stage was predisposed mainly by infection. Oxygen free radicals play an important role in the genesis and development of postburn MOF. In this study, it was revealed that antiperoxidation ability declined, active oxygen was increased, and lipid peroxidation became excessive after the burn injury. It was also found that oxygen free radical-mediated effects produced more serious damages in patients with MOF than those without, and also more in those died than the survivors. The hypoxanthine-xanthine oxidase system was a significant source of oxygen radicals after the burn injury. There were also significant changes in plasma TXA2 and PGI2 levels postburn. The marked increase in TXA2/PGI2 ratio indicated imbalance between TXA2 and PGI2, which was correlated well with burn size and closely related to the development of postburn MOF. The excessive production of TXA2 might trigger or accelerate the formation of microaggregates and thromboxane, subsequently leading to visceral damages and failure.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Burns; Female; Humans; Male; Malondialdehyde; Multiple Organ Failure; Shock, Traumatic; Superoxide Dismutase; Thromboxane B2; Xanthine Oxidase

We studied the effects of BN 50739, a novel PAF antagonist, in a rat model of traumatic shock. Pentobarbital anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma cathepsin D (4.2-fold), free amino-nitrogen (2.8-fold) and myocardial depressant factor (4.7-fold) activities and a survival time of 1.62 +/- 0.16 h. Treatment with BN 50739 (10 mg/kg, i.v.) 10 min post-trauma prolonged survival time to 3.14 +/- 0.44 h (p less than 0.01) and attenuated the accumulations of cathepsin D (5.8 vs. 12.5 U/ml, p less than 0.01), free amino-nitrogen (4.6 vs. 12.5 U/ml, p less than 0.001) and myocardial depressant factor (19.4 vs. 65.1 U/ml, p less than 0.001). Moreover, in washed rabbit platelets, BN 50739 inhibited PAF (1.85 nM)-induced aggregation (IC50: 50 nM) without affecting ADP (5 microM)-induced aggregation. In anesthetized rats, BN 50739 (10 mg/kg, i.v.) attenuated PAF (10-30 ng/kg, i.v.)-induced hypotension for longer than 5 h, without influencing acetylcholine (10 micrograms/kg, i.v.)-induced hypotension. These findings indicate that BN 50739 is a specific PAF receptor antagonist with a long duration of action in vivo. The beneficial effects of PAF antagonism on traumatic shock are significant in the present study, and are consistent with the concept that PAF is involved in the pathogenesis of traumatic shock.

Topics: Animals; Azepines; Blood Pressure; Cathepsin D; In Vitro Techniques; Male; Myocardial Depressant Factor; Nitrogen; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Rabbits; Rats; Rats, Inbred Strains; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Shock, Traumatic; Thromboxane B2; Triazoles

Traumatic shock was induced in anesthetized rats using the Noble-Collip method. This resulted in an abrupt decline in mean arterial blood pressure (MABP) and heart rate. Plasma cathepsin D activity increased sixfold, plasma thromboxane B2 (TxB2) concentration increased 2.5-fold, plasma myocardial depressant factor (MDF) activity increased 3.5 fold, and the mean survival time was 1.4 +/- 0.2 hours. Administration of the selective thromboxane synthetase inhibitor 5-(3-pyridinylmethyl) benzofuran-2-carboxylate (U-63,557A) (4 mg/kg) resulted in a significant improvement in survival time, 3.3 +/- 0.5, p less than 0.01. Plasma cathepsin D activity was not affected by U-63,557A (7.4 +/- 0.8 vs. 8.5 +/- 1.1 U/ml). However, both plasma and peritoneal fluid TxB2 concentration were significantly reduced and accumulation of the toxic peptide, MDF, was significantly blunted (69 +/- 6 vs. 40 +/- 5 U/ml, p less than 0.01). Our data indicate that blockade of thromboxane A2 (TxA2) production by selective synthetase inhibition is beneficial in trauma and support a role for TxA2 in the pathogenesis of circulatory shock.

Topics: Animals; Benzofurans; Blood Pressure; Cathepsin D; Dose-Response Relationship, Drug; Lysosomes; Male; Myocardial Depressant Factor; Oxidoreductases; Prognosis; Rats; Rats, Inbred Strains; Shock, Traumatic; Thromboxane B2; Thromboxane-A Synthase

Pinane thromboxane A2 (PTA2) an analog of thromboxane A2 that inhibits the formation of thromboxanes as well as antagonizes their biological actions, at an infusion rate of 1.0 mumole . kg-1 . h-1, prolonged survival in traumatic shock in rats. PTA2 also prevented the accumulation of thromboxane B2, the lysosomal protease, cathepsin D, and the cardiotoxic peptide MDF in the circulating blood.

Topics: Animals; Bicyclic Monoterpenes; Cathepsins; Myocardial Depressant Factor; Rats; Shock, Traumatic; Thromboxane A2; Thromboxane B2; Thromboxanes