triolein and Lung-Diseases

In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period.. Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated.. Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan.. These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Embolism, Fat; Losartan; Lung Diseases; Rats; Renin-Angiotensin System; Time Factors; Triolein

The action of histamine in oleic acid (OA)-induced injury was investigated using the isolated guinea pig lung perfused with blood-free media. OA infusion caused a significant increase in pulmonary arterial pressure, airway inspiratory pressure, lung weight, and protein flux across the alveolar-capillary barrier. These changes were dose dependent and caused injury regardless of the chemical form of OA (salt or free acid). Triolein (a neutral fat) infused at comparable emulsion particle size did not alter lung weight or bronchoalveolar lavage protein concentration in the perfused lung, suggesting that mechanical obstruction or emboli per se is not responsible for initiating early events in OA-induced injury. Infusion of OA caused a significant early histamine release into the venous effluent in the presence of aminoguanidine, a histamine catabolism inhibitor. Pretreatment with H1-receptor antagonists significantly attenuated OA-induced increase in lung weight and protein leak. These data support the link between OA-induced mast cell degranulation, histamine release, and OA-induced edema.

Topics: Animals; Guinea Pigs; Histamine; Histamine Antagonists; In Vitro Techniques; Lung Diseases; Male; Oleic Acid; Oleic Acids; Perfusion; Triolein

Twenty-two adult dogs were each given a single, 30-minute injection of 1.5 ml/kg body weight of pure triolein, and their pulmonary, hepatic, renal, and cerebral morphology was observed for 1, 2, 3, 4, 5, 6, 15, 24, and 48 hours; 3,4, and 5 days; 1 and 2 weeks; and 1 month after the injection. A picture of massive capillary occlusion by lipid droplets was followed by rapidly resolvable inflammatory pneumopathy of granulomatous type, leaving a normal lung at the end of the experiment. The cleaning of the capillaries may be attributed to the mechanical action of the blood flow and to the inflammatory reaction with evacuation of necrotic cells via the bronchial route. Transient pulmonary edema is attributed to increased pulmonary arterial pressure. There was no intravacular coagulation. The few pulmonary lesions observed after the triolein injection suggest that the chemical theory of neutral fat hydrolysis by pulmonary lipase and the toxicity of free fatty acids that are released should be reconsidered.

Topics: Animals; Brain; Dogs; Embolism, Fat; Kidney; Liver; Lung; Lung Diseases; Time Factors; Triolein