Primed stimulation of isolated perfused rabbit lung by endotoxin and platelet activating factor induces enhanced production of thromboxane and lung injury
| Autor: | C E McCall, W L Salzer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1990 |
| Předmět: |
Lipopolysaccharides
ARDS Thromboxane Indomethacin Blood Pressure Pulmonary Edema Pharmacology Lung injury In Vitro Techniques Capillary Permeability chemistry.chemical_compound Edema Medicine Animals Dazoxiben Platelet Activating Factor Lung business.industry Tumor Necrosis Factor-alpha Imidazoles Thromboxanes Drug Synergism General Medicine respiratory system medicine.disease Pulmonary edema Bridged Bicyclo Compounds Heterocyclic Pulmonary hypertension Thromboxane B2 Endotoxins Perfusion Hydrazines chemistry Immunology Fatty Acids Unsaturated lipids (amino acids peptides and proteins) Rabbits medicine.symptom business Research Article |
| Popis: | Bacterial sepsis often precedes the development of the adult respiratory distress syndrome (ARDS) and bacterial endotoxin (LPS) produces a syndrome similar to ARDS when infused into experimental animals. We determined in isolated, buffer-perfused rabbit lungs, free of plasma and circulating blood cells that LPS synergized with platelet activating factor (PAF) to injure the lung. In lungs perfused for 2 h with LPS-free buffer (less than 100 pg/ml), stimulation with 1, 10, or 100 nM PAF produced transient pulmonary hypertension and minimal edema. Lungs perfused for 2 h with buffer containing 100 ng/ml of Escherichia coli 0111:B4 LPS had slight elevation of pulmonary artery pressure (PAP) and did not develop edema. In contrast, lungs exposed to 100 ng/ml of LPS for 2 h had marked increases in PAP and developed significant edema when stimulated with PAF. LPS treatment increased capillary filtration coefficient, suggesting that capillary leak contributed to pulmonary edema. LPS-primed, PAF-stimulated lungs had enhanced production of thromboxane B2 (TXB) and 6-keto-prostaglandin F1 alpha (6KPF). Indomethacin completely inhibited PAF-stimulated production of TXB and 6KPF in control and LPS-primed preparations, did not inhibit the rise in PAP produced by PAF in control lungs, but blocked the exaggerated rise in PAP and edema seen in LPS-primed, PAF-stimulated lungs. The thromboxane synthetase inhibitor dazoxiben, and the thromboxane receptor antagonist, SQ 29,548, similarly inhibited LPS-primed pulmonary hypertension and edema after PAF-stimulation. These studies indicate that LPS primes the lung for enhanced injury in response to the physiologic mediator PAF by amplifying the synthesis and release of thromboxane in lung tissue. |
| Databáze: | OpenAIRE |
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