RESUMO
The effects of exogenously administered histamine phosphate (0.1 microgram per kg of body weight per min, or 90 microgram per hour) and endogenous histamine released by intravenous injection of 0.5 mg of Compound 48/80 on alveolar membrane permeability to substances of differing molecular weight (60 to 20,000 daltons) were studied using the in vivo saline-filled dog lung model. The half-time, i.e., the time required for 50 per cent equilibration between tracer substances in the blood compared to the saline-filled lung, was measured at baseline for urea, sucrose, and dextrans of varying molecular weight. The half-time decreased significantly for substances as large as 10,000 daltons after histamine infusion, and 20,000 daltons after injection of Compound 48/80. We conclude that histamine can increase alveolar epithelial permeability for substances of low molecular weight.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Histamina/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Animais , Dextranos/metabolismo , Cães , Espaço Extracelular/metabolismo , Histamina/sangue , Infusões Parenterais , Peso Molecular , Alvéolos Pulmonares/metabolismo , Sacarose/metabolismo , Ureia/metabolismoRESUMO
We observed two patients with aspirin (ASA) ingestion (blood levels of 87 and 56.5 mg/100 ml) who presented with noncardiogenic pulmonary edema (adult respiratory distress syndrome. To determine if ASA had a direct effect on the alveolar epithelial membrane, we established an in vitro isolated lung model and perfused it with platelet free plasma. T1/2 (in minutes), the time for 50% equilibration between the plasma and the saline filled lung, was determined before and after 500 mg salicylate infusion for various molecular weight dextrans. T1/2 decreased significantly (p less than 0.05) as follows: 3000 MW dextran, 2273 +/- 932 to 961 +/- 375; 40,000 MW dextran, 4059 +/- 1550 to 733 +/- 275; 70,000 MW dextran, 11,730 +/- 2750 to 7700 +/- 2230. Histamine levels in plasma and lung liquid did not change significantly with ASA infusion. We conclude that ASA directly increases alveolar epithelial permeability to dextrans less than 70,000 MW.
Assuntos
Alvéolos Pulmonares/efeitos dos fármacos , Salicilatos/farmacologia , Idoso , Animais , Dextranos , Cães , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Técnicas In Vitro , Masculino , Membranas/efeitos dos fármacos , Membranas/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Peso Molecular , Permeabilidade , Alvéolos Pulmonares/metabolismoRESUMO
Intravenous administration of ethchlorvynol (Placidyl) is known to produce noncardiogenic pulmonary edema in animals and humans. Since intrapulmonary sequestration of leukocytes has been observed to occur following injection of ethchlorvynol, we evaluated the role of these elements of the blood in producing pulmonary edema. In vivo studies in dogs showed intrapulmonary trapping of leukocytes, as evidenced by increasing leukocyte differences between blood from the pulmonary artery and arterial blood. In both animals with normal leukocyte counts and those depleted of leukocytes (less than 500 cells per millimeter), pulmonary edema occurred, as evidenced by increased pulmonary water after injection of ethchlorvynol. Preparations of isolated lung perfused with either whole blood or leukocyte-poor plasma had similar gains in weight following injection of ethchlorvynol, in spite of marked differences in leukocyte counts. We conclude that intrapulmonary sequestered leukocytes do not play a role in ethchlorvynol-induced pulmonary edema.
