Infusion Of Fat Emulsion Research Articles

Clinical and experimental studies on the internal secretion of the pancreas, with special regard to studies on its mechanism viewed from the proportional values of insulin and glucagon in the blood

For pathophysiologic studies on diabetics with special reference to the functional activities of pancreatic islets, the most reliable method of studies is the routine followups of blood levels of pancreatic hormones, i.e., insulin and glucagon. Owing to the technical difficulties, no direct estimation of both hormonal activities in the blood could be obtained until quite recently. In the 2nd Medical Department of Kobe Medical College, members of the research staff investigated the Insulin-like activity and Glucagon-like activity of blood (hereafter abbreviated as Insulin-value and Glucagon-value) with the rat diaphragm method and with the rat liver slice method. (Shimazu : The Japanese Journal of Gastro-Enterology, 57 827, 1960., Shinko : reported before the first ASIA and Oceania Regional Congress of Endocrinology in 1959.). The author has tried to clarify the mode of hormonal and nutritional control of endocrine activity of pancreatic islets by using these methods. As nutritional extra factors, the infusion of Amino-acid preparations and Fat emulsions were used. The results of various clinical and experimental observations are summarized as follows : 1. Intramuscular injection of 15 to 30 units Growth hormone to kittens, induced an elevation of Glucagon-value and a decrease of Insulin-value in 30 minutes. This phenomenon was more conspicuous with higher Growth hormone doses. 2. An injection of 30 to 50 units Growth hormone to normal dogs brought about an increase of Glucagon-value as the first step, followed by an increase of Insulin-value This was more conspicuous with higher Growth hormone doses. The blood sugar rate showed no regular increase or decrease as compared to the hormonal hypersecretion or hyposecretion. 3. Continuous intravenous drip of 5 to 15 units ACTH to dogs for 60 minutes induced no regular hormonal response from the pancreatic islets and effected no change of blood sugar level. Thus the single injection of ACTH seems to influence no regular response. 4. Intramuscular injection of 25 units ACTH to normal subjects induced an elevation of Glucagon-value and a lowering of Insulin-value in 2 hours, but in 3 hours these values returned to the pre-injection level. 5. Growth hormone, ACTH and Hydrocortisone were administered by in ramuscular injections for 6 to 8 days in dogs and then they were treated with continuous drip of 250c.c. 5% glucose solution. The responses of Insulin-value and Glucagon-value were determined simultaneously with the blood sugar response. Insulin-value showed a slight increase or almost no response, whereas Glucagon-value showed the high starting level from which no further distinct increase or decrease was observed. ACTH-treated dogs showed an elevation of Glucagon-value and blood glucose level following the drip and they nearly returned to the pretreatment level. Simultaneous observations of Insulin-value revealed no regular increase or decrease. Hydrocortisone-treated dogs showed an elevation of Glucagon-value in parallel with the elevation of blood sugar level, whereas Insulin-value showed a decrease. The reverse change wasobserved in Glucagon-value and Insulin-value as the blood sugar level went down. 6. Diabetogenicity of Growth hormone, ACTH and Hydrocortisone were compared with cach other from the aspect of Insulin Mobilizing Index formulated as follows : Insulin Mobilizing Index=_ (A-V one hour after glucose loading) - (A-V before glucose loading) Median blood glucose value× 100 where A-V means arterial blood glucose value-venous blood glucose value. Lowest Insulin Mobilizing Index was observed with Growth hormone, ACTH came next and with Hydrocortisone, an almost normal value was observed. 7. From the observation of Insulin-value and Glucagon-value in case of various endocrine disorders and in dogs treated with Growth hormone, ACTH and Hydrocortisone respectively,

Serum Lipids After Intravenous and Intragastric Fat Emulsion in Man

1. For the purpose of studying some mechanisms of lipid transport, the effect of fat emulsion on whole serum and subnatant serum lipids after single intragastric and intravenous administration and after daily intravenous infusion was studied in healthy young adults. 2. The level of whole serum neutral fat after intragastric administration of fat in the same subject did not result in as great an increase as was observed after intravenous administration. Following a single intravenous infusion of fat emulsion, subnatant serum neutral fat and free cholesterol reached a maximum eight hours after the start of the infusion. Increases were observed after intragastric administration of fat emulsion but not to the same degree as after intravenous infusions. During the first day, cholesterol and phospholipids decreased substatially in whole serum and subnatant after both intragastric and intravenous administration of fat emulsion, but returned to preinfusion levels on the second day of the experiment when no fat load was administered. 3. Daily intravenous administration of fat emulsion resulted in essentially similar patterns on the three days studied. Neutral fat and phospholipids peaked at the end of the infusion in the whole serum, and on successive days, the clearing rate of the infused fat emulsion decreased and the fasting level for neutral fat increased. Neutral fat in the subnatant serum reached its highest level four hours postinfusion along with an increase in cholesterol. The esterified cholesterol fraction dropped in serum from the beginning of the experiment and fell to its lowest point by the end of the third day, gradually returning to preinfusion levels by the sixth day. 4. The results of this study strongly suggest that the infused artificial chylomicrons are removed from the circulation essentially intact, reappearing, at least in part, as “soluble” lipoprotein. Serum cholesterol apparently becomes associated with the infused neutral fat thereby accounting for the immediate decrease in serum cholesterol. 5. The experiments described are discussed in the light of current knowledge in lipid transport.

Some Hematologic Changes in Patients Receiving Multiple Intravenous Infusions of Fat Emulsion

Some Hematologic Changes in Patients Receiving Multiple Intravenous Infusions of Fat Emulsion

Lipemia-induced acceleration of intravascular clotting. II. Effect of hypoprothrombinemia.

Summary and conclusions1) Bishydroxycoumarin-induced hypoprothrombinemia may result in a slight delay of fibrin clot in isolated venous segments of anesthetized dogs. 2) The hemorrhagic state produced by the drug fails to prevent acceleration of intravascular clotting caused by intravenous infusion of fat emulsion. This clot acceleration, therefore, may not operate through the mechanism of prothrombin conversion. 3) Our experiments lend support to the concept that anticoagulation with coumarin-type drugs is not synonymous with antithrombotic effect.

The permeability of liver and skin capillaries to lipids in the cat.

SUMMARYLymph was collected from the hepatic and leg ducts of cats before and after the intravenous infusion of artificial fat emulsions, homologous chyle and heterologous hypercholesterolaemic plasma.The fat particles of the artificial fat emulsion appeared in the hepatic lymph in quantities similar to those previously found for chyle. In the paw there was only a very little transfer of the particles of artificial fat emulsion and chyle from plasma to lymph even after injuring the skin by a thermal burn. The smaller lipid complexes of hypercholesterolaemic rabbit plasma, however, penetrated the capillary membrane and appeared in the lymph.The mechanisms of transfer in the liver and in the skin have been discussed.

The effect of soybean phosphatides on the erythrocyte sedimentation rate.

Summary.Intravenous infusion of fat emulsions, containing cottonseed oil, soybean phosphatides and Pluronic F 68 was found to lower the erythrocyte sedmientation rate in dogs. This effect was shown to be entirely due to the soybean phosphatides.

Intravenous fat as supportive therapy after severe injuries

A total of 302 units of a commercially prepared fat emulsion was given to twenty-eight patients. During five of the infusions, reactions such as nausea, chills and urticaria occurred. These were very minor and the patients showed no untoward effects when reinfused with fat emulsion on the following day. After eighteen infusions in various patients a benign rise in temperature to above 100.6 ° f. was noted. Only one patient showed a serious response. This consisted of jaundice after twenty-four infusions. At the present time it appears that moderate quantities of fat emulsion are safe for clinical use, but large quantities may evoke a severe response. Interference with liver function and the coagulation mechanism after intravenous fat emulsion infusions over a prolonged period is the primary problem requiring further study. Metabolic balance studies were carried out on several patients. Data on six typical patients show the protein-sparing effect of intravenous fat emulsion. This preparation appears to be a useful adjunct in injured patients and other patients who are unable to take adequate calories by mouth.

Comparison of Temperature Responses to Intravenous Infusions of Dextrose and Fat Emulsions

Forty-six daily infusions of 22.7 per cent dextrose were given in a four-day period to 12 healthy men. The following week, nine of these subjects each received three daily infusions of a 15 per cent fat emulsion. The dextrose and fat emulsion infusions were approximately equal in caloric content and caloric rates of infusion. There were no febrile responses. The temperature patterns of the control days, dextrose infusion days and fat infusion days were substantially the same.

TOLERANCE OF INFANTS AND CHILDREN TO FAT ADMINISTERED INTRAVENOUSLY

One hundred forty-six intravenous infusions of fat emulsions were given to 78 infants and children. In 15 subjects receiving 3 to 6 infusions on successive days, no significant changes occurred in concentration of nonprotein nitrogen, bilirubin or alkaline phosphatase in the serum; the cephahin flocculation test, concentration of urobilinogen in the urine and routine urinalysis were not abnormal. Three instances of increased values in the zinc turbidity test were noted. Four infants developed mild anemia. During infusions administered at an average rate of 5 ml/kg/hr for periods of 4 to 6 hours, concentrations of ketones in the blood increased an average of 7.1 mg/100 ml (1.2 mM/l) in non-fasted subjects and 13.2 mg/100 ml (2.3 mM/l) in fasted subjects. This is interpreted as suggestive evidence of utilization of fat during the infusion. Temperature elevations of more than 1.1°C (2°F) occurred during or after the infusion in 23.9% of infusions with a marked increase in frequency at infusion rates greater than 5 ml/kg/hr. Vomiting occurred in 12.3%. Other unfavorable reactions were uncommon.

Clinical experience with intravenous infusion of emulsified fat.

Abstract The results of 1,466 infusions of fat emulsion into 426 patients are presented and discussed. Emulsions containing 10 to 15 per cent of coconut, olive, peanut, and cottonseed oils, and synthetic triolein have been used. Data pertaining to such reactions as pyrogenicity, blood pressure, pulse, and chills are presented. The collected data are analyzed in regard to the overall effect of type of oil, concentration of oil, concentration of emulsifiers, presence of synthetic emulsifiers, quantitative and qualitative serum protein abnormalities of patients, and the effects of an antihistaminic on these reactions. Ninety-one per cent of the cottonseed oil infusions, 86 per cent of the coconut oil infusions, 82 per cent of the olive oil infusions, 85 per cent of the coconut oil-olive oil infusions, 83 per cent of the peanut oil infusions, 76 per cent of the synthetic triolein infusions were without pyrogen reaction. If one excludes temperature rises of 2.0 ° F., the percentage of successful infusions rises appreciably to 97 per cent for emulsions of cottonseed oil and 94 per cent for emulsions of synthetic triolein. A small number of other unfavorable reactions occasionally observed are discussed in detail, especially as they pertain to the intrinsic colloid character of fat emulsions. Substantial progress has been made toward the solution of the problems associated with the availability and use of emulsions of fat that can be given satisfactorily by vein.

Some observations of effects of intravenous fat emulsions on erythrocyte fragility.

Summary1. Intravenous infusion of fat emulsions causes increased mechanical fragility of dog and human red blood cells. 2. Spontaneous intravascular hemolysis has been seen in humans who have received these emulsions. 3. The possible causes of this phenomenon and its possible relationship to the “pyrogenic” effects of intravenous fat are discussed.