Increased intestinal protein permeability in a model of lung injury induced by phorbol myristate acetate.
Multiple nonpulmonary organ failure is a frequent complication of the adult respiratory distress syndrome (ARDS), and contributes significantly to the high mortality rate associated with this disorder. Although previous studies suggest that systemic organ injury may be an integral component of ARDS, little is known about the specific functional alterations that occur in these target organs. The present study was designed, therefore, to test the hypothesis that endothelial damage, as assessed by microvascular permeability changes, develops in systemic organs in a model of acute lung injury. To test this postulate, the microvascular permeability for total protein was estimated using the steady-state relationship between the lymph (CL) to plasma (Cp) protein concentration ratio (i.e., CL/Cp) and lymph flow in autoperfused cat ileum preparations. Specifically, CL/Cp was measured in five cats, 2 h after acute lung injury was induced by intravenously administered phorbol myristate acetate (PMA), 15 micrograms/kg, and the results were compared with those of seven time-matched control animals. Prior to PMA infusion, the PaO2/FIO2 ratio was 451 +/- 28 in both groups and remained unchanged (486 +/- 26) in the control group. By contrast, the PaO2/FIO2 ratio fell to 275 +/- 95 after PMA infusion (p less than 0.05). In addition, whereas CL/Cp was 0.099 +/- 0.008 in the control animals, it increased to 0.36 +/- 0.06 in the PMA-injured animals (p less than 0.01). In summary, this study demonstrated that in this model of acute lung injury produced by PMA-induced activation of circulating inflammatory cells, both acute lung injury and systemic organ injury (i.e., morphologic and permeability alterations) occurred.
St John
R C
RC
Department of Medicine, College of Veterinary Medicine, Ohio State University, Columbus.
Mizer
L A
LA
Weisbrode
S E
SE
Dorinsky
P M
PM
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002415:Cats; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects* / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D008208:Lymphatic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000503:physiopathology; D011506:Proteins / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D011506:Proteins; D013755:Tetradecanoylphorbol Acetate