BASIC NUTRITIONAL INVESTIGATION Dietary Fat Composition Alters Pulmonary Function in Pigs Robert R. Wolfe, PhD, Wenjun Z. Martini, PhD, Oivind Irtun, MD, Hal K. Hawkins, MD, PhD, and Robert E. Barrow, PhD From the Department of Surgery and the Department of Pathology, The University of Texas Medical Branch and Metabolism Unit, Shriners Burns Hospital, Galveston, Texas, USA OBJECTIVES: We investigated the effect of various dietary fats on pulmonary surfactant composition and lung function changes that occur before and after endotoxin infusion in pigs. METHODS: Eighteen pigs were assigned to three groups (n = 6 per group) to receive a diet of protein (20% of calories), carbohydrate (20% of calories), and fat (40% of calories). In one group the fat content consisted entirely of palmitic acid. In the second group, fat came from Intralipid, which provided predominantly linoleic acid. The third group was fed fish oil. Pigs were maintained on these diets for 21 d before the experiment. Cardiovascular and pulmonary functions were determined on day 22. Pigs then were infused with endotoxin (80 mg  kg -1  min -1 ) until the pulmonary arterial pressure reached a pressure similar to that found in trauma victims (45 to 50 mmHg). Cardiovascular and pulmonary function tests were then repeated, the animals killed, and the lungs removed for study. RESULTS: Compliance was reduced in the linoleate and fish-oil groups compared with the palmitate group before and after endotoxin. Compliance changes in pigs fed the linoleate and fish-oil diets were consistent with significant increases in lung wet:dry weight ratios, increased CO 2 retention, histologic evidence of vascular congestion, intra-alveolar edema, and alveolar septa thickening. Changes in surfactant phos- phatidylcholine composition between groups were consistent with the notion that increased unsaturated fatty acids could affect surfactant function. CONCLUSIONS: We concluded that the common practice of providing calories in the form of polyunsat- urated fatty acids to critically ill patients carries the risk of being detrimental to lung function. Nutrition 2002;18:647– 653. ©Elsevier Science Inc. 2002 KEY WORDS: surfactant, lung compliance, dietary fatty acids INTRODUCTION Lung dysfunction is an important cause of morbidity and mortality in critically ill patients. A deficiency or change in the composition of the lung surfactant complex may contribute to this response. Pulmonary surfactant plays an important physiologic role by de- creasing alveolar surface tension and in keeping the lungs dry. Clinical circumstances in which impaired lung function is common (e.g., sepsis and acute pancreatitis) are associated with decreased surfactant production. 1–3 Further, changes in the composition of the surfactant complex can also affect lung function. Dipalmi- toylphosphatidylcholine is the most active phospholipid in this complex. The substitution of unsaturated fatty acids such as oleate or linoleate can affect the surface tension–lowering capacity of phosphatidylcholine (PC) and lung compliance. 4 The most well- recognized circumstance in which altered composition is related to respiratory distress is in premature infants who have a reduced proportion of palmitate in the lung surfactant PC. 5 Similar changes in pulmonary surfactant composition also have been reported in patients with acute respiratory distress syndrome. 6 Substitution of unsaturated fatty acids for saturated fatty acids can decrease the surface tension–lowering capacity of surfactant and its ability to keep the lungs dry. 7,8 Consequently, the amount and composition of surfactant can potentially affect lung function. Under normal circumstances there is sufficient reserve of sur- factant in the lungs so that perturbations such as normal stress or dietary manipulations that might affect surfactant quantity or com- position will have a minimal effect on lung function. However, in a clinical circumstance in which the lung reserves are compro- mised, a deficiency in the amount or composition of surfactant might have devastating results. For example, endotoxin injection caused an almost immediate increase in the mean pulmonary artery pressure, microvascular permeability, 9 and lung compliance. 10 Thus, a change in lung surfactant superimposed on an already- compromised lung function likely would become clinically significant. We recently reported that the plasma free fatty acids (FFAs) are the principal precursors for synthesis of pulmonary PC, 11 even when peripheral lipolysis is suppressed by high rates of glucose intake. 12 It could, therefore, be anticipated that dietary manipula- tions that alter the fatty acid profile in plasma also might cause corresponding changes in lung PC composition. If true, this could have significant clinical implications because conventional nutri- tion in critically ill patients often includes a lipid-based emulsion derived from soy beans in which over half the fatty acids are linoleate (18:2), and nutrition support with this formulation causes the proportion of total plasma FFAs represented by linoleate to increase. 13 Thus, nutrition support of critically ill patients with a lipid-based system could decrease the proportional contribution of palmitate to lung surfactant PC, thereby inadvertently contributing This study was supported by Shriners Hospital for Children–Galveston Burns Hospital grants 8550, 8490, and 8450. Correspondence to: Robert R. Wolfe, PhD, Department of Surgery, Shri- ners Burns Hospital, 815 Market Street, Galveston, TX 77550, USA. E-mail: rwolfe@utmb.edu Nutrition 18:647– 653, 2002 0899-9007/02/$22.00 ©Elsevier Science Inc., 2002. Printed in the United States. All rights reserved. PII S0899-9007(02)00785-2