Fatty Acid Saturation of Albumin Used in Resuscitation Fluids Modulates Cell Damage in Shock : in vitro Results Using a Novel Technique to Measure Fatty Acid Binding Capacity

The efficient sequestration of hemoglobin by the red blood cell membrane and the presence of multiple hemoglobin clearance mechanisms suggest a critical need to prevent the buildup of this molecule in the plasma. A growing list of clinical manifestations attributed to hemoglobin release in a variety of acquired and iatrogenic hemolytic disorders suggests that hemolysis and hemoglobinemia should be considered as a novel mechanism of human disease. Pertinent scientific literature databases and references were searched through October 2004 using terms that encompassed various aspects of hemolysis, hemoglobin preparations, clinical symptoms associated with plasma hemoglobin, nitric oxide in hemolysis, anemia, pulmonary hypertension, paroxysmal nocturnal hemoglobinuria, and sickle-cell disease. Hemoglobin is released into the plasma from the erythrocyte during intravascular hemolysis in hereditary, acquired, and iatrogenic hemolytic conditions. When the capacity of protective hemoglobin-scavenging mechanisms has been saturated, levels of cell-free hemoglobin increase in the plasma, resulting in the consumption of nitric oxide and clinical sequelae. Nitric oxide plays a major role in vascular homeostasis and has been shown to be a critical regulator of basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation. Thus, clinical consequences of excessive cell-free plasma hemoglobin levels during intravascular hemolysis or the administration of hemoglobin preparations include dystonias involving the gastrointestinal, cardiovascular, pulmonary, and urogenital systems, as well as clotting disorders. Many of the clinical sequelae of intravascular hemolysis in a prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria, are readily explained by hemoglobin-mediated nitric oxide scavenging. A growing body of evidence supports the existence of a novel mechanism of human disease, namely, hemolysis-associated smooth muscle dystonia, vasculopathy, and endothelial dysfunction.

Background: The involvement of lipolytic enzymes and liberated fatty acids in ethiology of acute pancreatitis (AP) has been implicated. Aim: To analyze the level of FFA in the patients with AP in relation to severity of the disease. Material and Methods: The study included 36 patients with acute edematous AP (group I), 29 patients with necrotizing AP: 16 without (group IIA) and 13 with complications (group IIB), and 12 control subjects. Serum levels of total FFA (by enzymatic method) and the individual fatty acids of the FFA pool (by gas-liquid chromatography) were measured during the first 4 days after admission. Results: A significant increase in the mean total serum FFA was noted for all the groups with the highest values on admission (p < 0.02–0.01). The per cent contribution was significantly higher as compared to control group for oleic acid (group I, p < 0.02, group IIA, p < 0.05, group IIB, p < 0.005), linoleic acid (group IIB, p < 0.02) and arachidonic acid (group IIA, p < 0.05, group IIB, p < 0.02). Significantly lower percentage was noted for stearic acid (all three groups: p < 0.01, p < 0.005, p < 0.01, respectively) and for palmitic acid (only group IIB: p < 0.005). The ratio of saturated to polyunsaturated fatty acids was significantly lower than in control group on each day of study for group IIB only (p < 0.005–p < 0.001). Conclusion: Polyunsaturated fatty acids, mainly linoleic and arachidonic, may be involved in the development of complications in acute pancreatitis.

In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either saline or nicotinic acid (NA) to deplete their plasma FFA pool, followed by an intravenous bolus of glucose. NA treatment resulted in a fall in basal insulin concentrations of 35 and 45% and in the area under the insulin response curve (area under the curve [AUC]) to glucose of 47 and 42% in the 24- and 48-h fasted individuals, respectively. The 48-h fasted subjects underwent the same procedure with the addition of a coinfusion of Intralipid plus heparin (together with NA) to maintain a high concentration of plasma FFAs throughout the study. The basal level and AUC for insulin were now completely normalized (C-peptide profiles paralleled those for insulin). To assess the effect of an overnight fast, nonobese (n = 6) and obese (n = 6) subjects received an infusion of either saline or NA, followed by a hyperglycemic clamp (200 mg/dl). The insulin AUC in response to glucose was unaffected by lowering of the FFA level in nonobese subjects, but fell by 29% in the obese group. The data clearly demonstrate that in humans, the rise in circulating FFA levels after 24 and 48 h of food deprivation is critically important for pancreatic beta-cell function both basally and during subsequent glucose loading. They also suggest that the enhancement of GSIS by FFAs in obese individuals is more prominent than that seen in their nonobese counterparts.