ozagrel and Burns

Thromboxane A2 (TxA2) is a key mediator in the pathophysiology of severe burns and sepsis. This study was performed to assess the potential benefits of TxA2 synthetase inhibition and TxA2 receptor blockade in sepsis after severe thermal injury.. Pigs with left atrial, aortic, and pulmonary artery catheters received a 40 percent third-degree burn and, 24 hours later, 100 micrograms per kg Escherichia coli endotoxin. The antagonist treatment (BM) group was treated with the TxA2 receptor antagonist BM 13.177, the synthetase treatment (OKY) group with the TxA2 synthetase inhibitor OKY-046, and the control group received saline solution placebo. Another group without burn or endotoxin was used to assess the side effects of BM 13.177.. Both drugs significantly attenuated the changes in pulmonary vascular resistance index, cardiac index, arterial PO2, shunt, oxygen delivery, and oxygen consumption seen after endotoxin. However, cardiac index was significantly decreased in group BM before endotoxin. In healthy pigs, BM 13.177 decreased cardiac index and oxygen delivery and increased the pulmonary vascular resistance index.. TxA2 synthetase inhibitors and TxA2 receptor blockers are potentially useful in sepsis after severe burns. Comparison between drugs was complicated by the adverse effects of the antagonist, and further investigation with other antagonists is needed.

Topics: Animals; Blood Circulation; Blood Pressure; Burns; Cardiac Output; Disease Models, Animal; Endotoxins; Escherichia coli Infections; Female; Lipopolysaccharides; Lung; Methacrylates; Oxygen Consumption; Pulmonary Artery; Pulmonary Gas Exchange; Receptors, Thromboxane; Sulfonamides; Swine; Swine, Miniature; Thromboxane-A Synthase; Vascular Resistance

It is known that thromboxane (TX)B2, the metabolite of the potent vasoconstrictor TXA2, is elevated markedly in the serum of the patients immediately postburn. We had shown that extensive thermal injury causes a reduction in mesenteric blood flow that can lead to bacterial translocation from the intestine. In this study, we tested the hypothesis that the TX synthetase inhibitor, OKY-046, prevents increased mesenteric vascular resistance (MVR) and decreases the rate of translocation of bacteria seen after extensive thermal injury. Pigs in groups 1 (n = 6) and 2 (n = 6) had third degree burns of 40 per cent total body surface area under general anesthesia and were resuscitated according to the Parkland formula. Pigs in group 2 received 10 milligrams per kilogram of OKY-046 as a bolus just before the burn and 10 grams per kilogram per minute for 16 hours as a continuous infusion. Pigs in group 3 (control, n = 6) underwent general anesthesia only and received daily maintenance fluids of lactated Ringer's solution, 2 milliliters per kilogram per hour. OKY-046 prevented the significant increase in MVR seen during the first eight hours after burn. The total peripheral resistance (TPR) showed an early increase and a late decrease in the burn group, while the cardiac index (CI) and temperature (T) significantly increased after 24 hours. Administration of OKY-046 kept TPR, Cl, and T remarkably stable. OKY-046 reduced the rate of translocation of bacteria seen in the burn group from 67 to 17 per cent. Our results show that the blockade of thromboxane synthesis by OKY-046 prevented the early mesenteric vasoconstriction and the late hyperdynamic response seen after thermal injury and was useful in reducing the incidence of postburn translocation of bacteria.

Topics: Animals; Bacteria; Burns; Female; Hemodynamics; Intestines; Methacrylates; Splanchnic Circulation; Swine; Thromboxane-A Synthase; Time Factors; Vascular Resistance

A full skin thickness burn covering 35 per cent of the total body surface area was inflected on the back of rabbits. The animals were divided into seven groups and the effectiveness of OP-41483, aspirin (ASA), OKY-046 and CV-3988 was studied. All rabbits died between 8 and 24 h after injury in the no therapy group. Renal function tests in this group showed a decrease in Cler and an increase in FENa and CH2O. Such changes were improved slightly with infusion therapy. On the contrary, with OP-41483, OKY-046 and ASA, distinct improvements were observed (in order of extent of improvement), but with CV-3988 the improvements were rather small. As a result these drugs may also be effective in preventing organ failure after burn injury, but as such changes presumably occur immediately after the burn it is considered that a fast-acting agent such as OP-41483 is the most effective form of treatment.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Aspirin; Blood Coagulation; Blood Platelets; Burns; Epoprostenol; Fibrinolysis; Kidney; Methacrylates; Phospholipid Ethers; Platelet Activating Factor; Platelet Aggregation Inhibitors; Rabbits; Thromboxane-A Synthase