A thromboxane analog increases pulmonary capillary pressure but not permeability in the perfused rabbit lung.
Thromboxane has been implicated as a mediator of pulmonary hypertension and pulmonary edema in acute respiratory failure. Pulmonary edema may result from increased pulmonary capillary hydrostatic pressure or from increased pulmonary vascular permeability. We therefore studied the effects of a stable thromboxane analog, U46619, on these two parameters in the perfused rabbit lung. Pulmonary capillary pressure was measured by the double vascular occlusion method, and pulmonary vascular permeability was estimated by measurement of the pulmonary fluid filtration coefficient (Kf). U46619 infusion produced pulmonary hypertension and lung weight gain; increased both the arterial (precapillary) and venous (postcapillary) components of pulmonary vascular resistance; and increased pulmonary capillary pressure from 4.7 +/- 0.5 to 9.0 +/- 0.7 mmHg (P less than 0.01). The isogravimetric pressure (equivalent to the capillary pressure corresponding to no lung weight gain) was 4.0 +/- 0.4 mmHg before U46619 and 4.6 +/- 0.4 mmHg during U46619. Therefore, U46619 significantly increased capillary pressure above isogravimetric pressure and resulted in the development of pulmonary edema. U46619 did not affect vascular permeability as measured by Kf. We conclude that pulmonary venoconstriction resulting in increased pulmonary capillary hydrostatic pressure is the major mechanism by which thromboxane produces pulmonary edema in isolated lungs.
Wakerlin
G E
GE
Department of Anesthesia, Stanford University Medical Center, California 94305.
Benson
G V
GV
Pearl
R G
RG
D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000209:etiology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D015430:Weight Gain
D011450:Prostaglandin Endoperoxides, Synthetic