Hiroshi Nishiwaki

Apolipoprotein C-II Modifications Associated with an Infusion of Artificial Lipid Particles

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.

Influences of an Infusion of Lipid Emulsion on Phagocytotic Activity of Cultured Kupffer's Cells in Septic Rats:

An experimental study was undertaken to study the influences of an infusion of lipid emulsion on phagocytosis of Kupffers cells in septic rats. Sepsis was induced in 13 rats by ligating the cecum. Five of them received glucose as the sole nonprotein calorie (septic-glucose group), four of the rats received 25% of the nonprotein calorie with lipid emulsion, Intralipid (septic-lipid group), and the remaining four rats did not receive any intravenous solution and were allowed access to water (septic-fasted group). Another four rats which received neither intravenous solution nor ligation of the cecum served as the control group. The intravenous infusion was carried out for 72 hr. The phagocytotic activity of Kupffers cells was determined by the ability to engulf latex particles with a size of 1.09 micron, in vitro. The phagocytotic activity was enhanced by the presence of sepsis but it was inhibited by starvation. The difference in the phagocytotic activity between the septic-glucose group and the septic-lipid group was not significant. These results suggest that, insofar as an in vitro study is concerned, a 72-hr infusion of lipid emulsion at a rate of 25% of the total nonprotein calorie does not influence the phagocytotic activity of cultured Kupffers cell obtained from septic rats.

Clearance Rate of Intravenously Administered Lipid Emulsion in Canine Endotoxemia

The effect of endotoxemia on the initial catabolism of intravenously given lipid emulsion was investigated in dogs. Two types of endotoxemia were prepared. One was produced by peritonitis which was established by ligation of the artery and vein of an isolated intestine (group 1, n = 6). The other was made by an intravenous injection of Escherichia coli lipopolysaccharide in a dose of 1.5 mg/kg of body weight (group 2, n = 6). Group 1 showed evident peritonitis with a positive limulus test 48 hr after the procedure, but no significant changes of blood sugar level and lactate/pyruvate ratio, while group 2 demonstrated profound hypoglycemia, significant elevation of lactate/pyruvate ratio, and low arterial pressure 3 to 5 hr after the injection of lipopolysaccharide. The clearance rate of intravenously administered lipid emulsion (K value) of group 1 before the peritonitis was 0.0105 +/- 0.0017 and after the peritonitis it was 0.0105 +/- 0.0019. The difference was not significant, while the K value of group 2 which was 0.0133 +/- 0.0056 before the injection of lipopolysaccharide decreased significantly to 0.0069 +/- 0.0024 after the injection of lipopolysaccharide. These results suggest that, in case of endotoxemia with normally maintained oxidation-reduction potential, the initial catabolism of intravenously given lipid emulsion is kept in a normal level, while oxidation-reduction potential is impaired, it is inhibited.

Clearance rate of intravenously administered lipid in postoperative patients.

Elimination rate (K) of intravenously given triglyceride was studied in seventeen patients who underwent elective abdominal operations, and levels of adrenaline, noradrenaline, insulin and blood sugar were simultaneously measured, as stress-indices. All these indices, except for the insulin/blood sugar ratio, increased post-operatively. The postoperative K value increased significantly in comparison with the preoperative value. There was no significant correlation between K value and any of the stress-indices. These results suggest that the initial catabolism of the lipid emulsion triglyceride is enhanced by surgical stress.

Effects of Exogenous Catecholamines on Glucose and Fat Metabolism and on Triglycerides in the Rat Liver during Total Parenteral Nutrition

An experiment was undertaken to investigate the effects of a continuous infusion of catecholamines on glucose and fat metabolism as well as on nitrogen balance and the amount of triglycerides in the rat liver. The animals were nourished by total parenteral nutrition for 5 days and divided into six groups (n = 5 in each group) on the basis of nonprotein calories given with or without an infusion of catecholamines: group G received 100% of nonprotein calories with glucose, group F received 50% of nonprotein calories with glucose, and the remaining 50% with lipid emulsion, groups Epi-G and Epi-F received epinephrine (1 microgram/kg body weight/min) in addition to the same total parenteral nutrition solution as group G or F, and groups Nor-G and Nor-F received norepinephrine (1 microgram/kg/min) in a similar manner. Each group was administered the same number of total calories (252 cal/kg/day) and the same amount of nitrogen (1.49 g/kg/day). Nitrogen balance was better in group G than in group F. Under catecholamine infusion, there were no significant differences in nitrogen balance between groups Epi-G, Nor-G, Epi-F, and Nor-F, but this parameter improved significantly in group Nor-F in comparison to group F. Liver triglycerides was higher in groups Epi-G and Nor-G than in groups Epi-F and Nor-F. Liver triglycerides was directly related to the blood sugar level. These results indicate that nitrogen conservation is improved with lipid emulsion and that glucose rather than lipid plays a significant role in the genesis of fatty liver, when they are administered under catecholamine-induced stress.

Effects of hemodynamic changes induced by hyper- or hypothermia on intravenous lipid clearance rate and lipoprotein lipase activity in dogs

Hyper- and hypothermia was induced in dogs by peritoneal perfusion with warm or cold Lactate-Ringers solution, the objective being to alter cardiac output. Changes in cardiac index, intravenous lipid clearance rate (K-value), and lipoprotein lipase (LPL) activity, concomitantly with changes of the temperature of the mixed venous blood were investigated. The cardiac index increased significantly with the hyperthermia and there was a close correlation between the cardiac index and the K-value. The LPL activity did not change significantly with changes in blood temperature, and the correlation between the LPL activity and the K-value was not significant. The hemodynamics has to be considered when attempting to discuss the intravenous lipid clearance rate.

Effects of total parenteral nutrition on the development of intestinal endotoxemia in rats: a comparison between glucose and lipid

The effects of parenteral nutrition (PN) and of the difference in the PN regimens between glucose and lipid emulsion on the development of endogenous endotoxemia were studied in 40 Wister rats. Endotoxemia was induced by occluding the superior mesenteric vein (SMV) for 30 min. The plasma endotoxin in the portal blood at the time of the release of the SMV occlusion and that in the arterial blood 10 min after the release were quantified. Twenty of the 40 rats had received PN for 48 hr prior to the SMV occlusion. Ten of these 20 rats received the total nonprotein calorie (TNPC) solely with glucose, and the other 10 rats received 25% of the TNPC with lipid emulsion. Ten rats had been allowed free access to lab food until the SMV occlusion. The remaining 10 rats underwent neither the SMV occlusion nor PN, and served as the control group. Both the portal and the arterial endotoxin increased after the release of the SMV occlusion, however the portal endotoxin was higher than that of the arterial one. Both the portal and the arterial endotoxin of the rats supported by PN were significantly lower than those of the rats nourished by lab food, while they were higher than the control values. The difference in the PN regimens did not cause any alteration in the endotoxin levels. These results indicate that the development of intestinal endotoxemia was not influenced by the difference in the PN regimens, but it was rather influenced by a presence of intestinal content.

Nitrogen-sparing effect of lipid emulsion in septic dogs

Effects of intavenously administered lipid emulsion on the nitrogen balance in dogs with intraabdominal infection were investigated. The nitrogen balance in dogs supported by parenteral nutrition (PN) with glucose alone was superior to that in dogs supported by PN with glucose and lipid emulsion, in the absence of intraabdominal infection. On the other hand, the nitrogen balance in dogs supported by PN with glucose and lipid emulsion was superior to that with glucose alone, in the presence of intrabdominal infection. Dogs with intraabdominal infection had an insulin-resistance inability to effectively utilize glucose.