Thromboxane synthetase inhibition and thromboxane receptor blockade preserve pulmonary and circulatory function in a porcine burn sepsis model.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Iglesias
G
G
Shriners Burns Institute, Galveston, TX.
Zeigler
S T
ST
Lentz
C W
CW
Traber
D L
DL
Herndon
D N
DN
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002056:Burns / Q000503:physiopathology*; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008689:Methacrylates / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects; D011651:Pulmonary Artery; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000627:therapeutic use; D013552:Swine; D013556:Swine, Miniature; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D008070:Lipopolysaccharides; D008689:Methacrylates; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C040624:sulotroban; D013930:Thromboxane-A Synthase; C034364:ozagrel