RESUMO
We investigated in a porcine model whether omega-3 fatty acids modify the physiological response to sepsis. For 8 days, 16 male pigs were fed a diet containing 18% fat by weight enriched with either omega-3 or omega-6 fatty acids (FA). A group of six pigs receiving their regular diet served as controls. The omega-3 FA-supplemented pigs had elevated levels of omega-3 FA in their serum-free FA, serum phospholipid (PL), and platelet PL levels compared with either of the other groups. On the ninth day, the unanesthetized pigs were injected with 0.3 mg/kg of endotoxin (Escherichia coli) intravenously. The animals had a significant decrease in their arterial O2 pressure (PaO2) [from 84.4 +/- 6.8 (SD) to 64 +/- 9.4, and from 83.1 +/- 7.2 to 55.9 +/- 6.3 mmHg in the omega-6 FA and regular diet groups, respectively]. The PaO2 did not decrease in the omega-3 FA pigs. The omega-3 FA group had significantly lower pulmonary vascular resistance (541 +/- 205 dyn.s.cm-5) 20 min after endotoxin compared with either the omega-6 FA or regular diet groups (797 +/- 233 and 1,102 +/- 552 dyn.s.cm-5, respectively) and more normal blood pressure compared with the other two groups. Plasma thromboxane (Tx) B2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) levels were lowest in the omega-3 FA diet group and highest in the regular diet group.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Gorduras na Dieta/farmacologia , Endotoxinas/toxicidade , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Hemodinâmica/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Análise de Variância , Animais , Ácido Araquidônico/análise , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Óleo de Milho/farmacologia , Ácido Eicosapentaenoico/análise , Escherichia coli , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Óleos de Peixe/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ácido Linoleico , Ácidos Linoleicos/análise , Masculino , Orquiectomia , Fosfolipídeos/sangue , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiologia , Análise de Regressão , Suínos , Resistência Vascular/efeitos dos fármacosRESUMO
Since an omega 3 fatty acid (FA) diet may have beneficial effects in inflammatory processes, we tested the hypothesis that the physiologic response to sepsis could be modified by altering the eicosanoid precursor pool via an omega 3 FA diet. Two groups (n = 8) of pigs were prefed for 8 days either an omega 3 FA or an omega 6 FA diet (Weaner Pig Feed with either menhaden or corn oil to produce a eucaloric feed with 15% fat) and then injected with live Escherichia coli. The omega 3 FA diet increased the concentration of eicosapentainoic acid (EPA, 20:5 omega 3) in plasma lipids, and increased the ratio of EPA to arachidonic acid (AA, 20:4 omega 6) in platelets from 1:20 to 1:1 over the 8 days. Following the injection of bacteria, there was a fall in PaO2 and blood pressure that was attenuated (p less than 0.05) by the omega 3 FA diet. The omega 3 FA diet, compared to the omega 6 FA diet, also attenuated the rise in thromboxane B2 (3.0 +/- 1.1 vs 12.9 +/- 5.7 ng/mL) and 6 keto-PGF1 alpha (0.8 +/- 0.5 vs 1.7 +/- 1.1 ng/mL) associated with bacteremia. We conclude that dietary omega 3 FA attenuated the physiologic response to sepsis, possibly by modifying arachidonic acid metabolism.
Assuntos
Sistema Cardiovascular/fisiopatologia , Gorduras Insaturadas na Dieta/uso terapêutico , Infecções por Escherichia coli/fisiopatologia , Óleos de Peixe/uso terapêutico , Pulmão/fisiopatologia , Sepse/fisiopatologia , 6-Cetoprostaglandina F1 alfa/sangue , Animais , Ácido Araquidônico , Ácidos Araquidônicos/sangue , Plaquetas/metabolismo , Pressão Sanguínea , Ácido Eicosapentaenoico/sangue , Infecções por Escherichia coli/complicações , Lipídeos/sangue , Masculino , Norepinefrina/sangue , Oxigênio/sangue , Edema Pulmonar/etiologia , Sepse/complicações , Sepse/dietoterapia , Suínos , Tromboxano B2/sangueRESUMO
Diets high in n-3 fatty acids appear to have an anti-inflammatory effect, which is thought to be due to decreased macrophage prostaglandin (PG) and thromboxane (Tx) production after incorporation of these fatty acids into cell membrane phospholipids. The effect of n-3 fatty acids incorporation on macrophage monokine release in response to septic stimuli is not well established. Kupffer cells, the fixed macrophages of the liver, were obtained from rats fed diets with fat sources derived from corn oil (CO, control), fish oil (FO, high in n-3 fatty acids), or safflower oil (SO, high in n-6 fatty acids) for 2 or 6 weeks. After exposure to bacterial lipopolysaccharide, Kupffer cells from rats fed FO for 2 or 6 weeks produced less PG and Tx than Kupffer cells from rats fed CO or SO. After 2 weeks of defined diets, interleukin-1 (IL-1) and tumor necrosis factor release were not affected by dietary fat source. In contrast, after 6 weeks of feeding, Kupffer cells from both the FO and the SO groups released less IL-1 and tumor necrosis factor when triggered by lipopolysaccharide than Kupffer's cells from animals fed the control diet that contained CO. These data suggest that altered monokine release from macrophages may contribute to the anti-inflammatory effect of diets high in n-3 fatty acids. Also shown in our results is that prolonged changes in membrane phospholipid content induced by dietary fat source can influence not only PG and Tx production but monokine release as well.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Células de Kupffer/fisiologia , Animais , Escherichia coli , Ácidos Graxos Insaturados/administração & dosagem , Óleos de Peixe/farmacologia , Interleucina-1/biossíntese , Células de Kupffer/imunologia , Lipopolissacarídeos/farmacologia , Linfocinas/imunologia , Lipídeos de Membrana/fisiologia , Prostaglandinas/biossíntese , Ratos , Ratos Endogâmicos , Tromboxanos/biossíntese , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Polyunsaturated fatty acid (PUFA) profiles are abnormal in a variety of clinical conditions that are commonly seen in the surgical intensive care unit. PUFA profiles in the serum phospholipids were studied by capillary gas chromatography in 22 critically ill, hypermetabolic surgical intensive care unit patients. All patients received continuous total parenteral nutrition (TPN) by central vein with trace elements and vitamins. Eleven patients received daily supplementation with 50 gm of safflower oil-based lipid emulsion (TPN + L group). No lipid was administered in the other 11 patients (TPN). Both groups showed deficiencies in 18:2 omega 6 linoleic acid from the time of onset of TPN. In TPN the deficiency was progressive; in the TPN + L group, lipid administration prevented this progression but did not restore 18:2 omega 6 levels to normal. In the TPN group levels of 18:1 omega 9 and its metabolite 20:3 omega 9 (the triene of deficiency) increased over time, consistent with a mild essential fatty acid deficiency. These changes in omega 9 acids were not seen with lipid supplementation. Despite low levels of 18:2 omega 6 in both groups, the levels of omega 6 metabolites were normal or increased. Levels of 20:4 omega 6 (arachidonate) remained normal or slightly decreased in the TPN group but were decreased in the TPN + L group. Levels of arachidonate metabolites, in particular 22:5 omega 6, were increased in the lipid-supplemented group. We concluded that stressed patients receiving TPN develop mild essential fatty acid deficiency that is only partially correctable by lipid supplementation and that administration of supplemental lipid to these patients stimulates arachidonic acid conversion to 22:5 omega 6.