Thromboxane receptor blockade with BM 13,177 following toxic airway damage by smoke inhalation in sheep.
Thromboxane may play an important role in the pathogenesis of smoked mediated injury. We studied this possibility in 13 chronically instrumented sheep, which had the left lung exposed to smoke. BM 13,177, a thromboxane receptor antagonist, was given intravenously to six animals prior to smoke inhalation and during the experimental period. Seven animals received the vehicle. All animals were studied for 24 h under ventilatory support, then killed prior to harvesting lung tissue. Airway peak and plateau pressures in the vehicle-treated animals were elevated by 27% and 25% from baseline at 24 h post smoke inhalation. Concomitantly, the left pulmonary vascular resistance index rose continuously throughout the study period (baseline = 822 +/- 58; 24 h = 1819 +/- 84 dyn.s.cm-5.m2).BM 13,177 treatment completely prevented the rise in airway pressure, while the left pulmonary vascular resistance index was significantly attenuated (baseline = 726 +/- 79; 24 h = 1470 +/- 158 dyn.s.cm-5.m2) resulting in a significantly higher percentage of cardiac output being delivered to the smoked lung, compared to vehicle-treated animals. Thromboxane receptor blockade did not prevent smoke induced pulmonary edema formation. There was likewise no effect of BM 13,177 on the systemic hemodynamic changes seen following smoke inhalation. There was a decrease in cardiac index and an increase in systemic vascular resistance index in both groups. We conclude that smoke induced changes in airway and pulmonary vascular resistances may be mediated by thromboxanes. However, thromboxanes appear to play no role in the development of pulmonary edema and elevation of systemic vascular resistance following smoke inhalation injury.
Loick
H M
HM
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77550-2788.
Traber
L D
LD
Tokyay
R
R
Linares
H A
HA
Rogers
S
S
Flynn
J T
JT
Traber
D L
DL
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002263:Carboxyhemoglobin / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C040624:sulotroban; D002263:Carboxyhemoglobin; D010100:Oxygen