- Email: [email protected]
Hypertriglyceridaemic clamp: a new model for studying lipid metabolism
NUTRITIONAL ASSESSMENT AND METHODS
0.1
vmic
clamp: a new model for studying
MidYA. Cmpsnt& J. M. Kinney, VS. Siderova, M. Richelle, H. Nishitvaki, T. Olivecrone and R. J. Deckebaum Univ. tibre de Bruxeffes, Belgium Lipid infusions areoftenused for studying the metabolism of exogenous, but also endogenous hypertriglyceridaemia. Bolus injections allow to measure triglyceride (TG) elimination from intact particles. However, further catabolic steps lead to the formation of remnants removed at a slower rate by the liver. Hence, mixing of particles at different stage of catabolism occurs during lipid infusions, with a progressive enrichment in remnants. At the same time, lipid components are exchanged between exogenous particles and endogenous lipoproteins as well as cell membranes. Keeping plasma TG concentration stable during a prolonged period might offer a great advantage for studying the influence of lipid composition on these complex processes. In 6 voiunteers, endogenous lipid levels were stabilized after 3 h of combined glucose and aminoacids infusion (0.16 and 0.05g/kg.h, respectively). At that point, 2 10% lipid emulsions (em.) A and B, differing by their phospholipid (PL) content (12 and 69/l) were infused for the next 5 h. The proposed plasma levels of 6 and 11 mmol TG/I were reached after infusing both em. for 19 and 33 min at a primed rate of 1 g TGikg.h; infusion rates were then reduced and adjusted in relation to enzymatic determinations performed every E-15 min. TG levels were clamped at 6.14 + 0.13 and 5.81 + 0.16 mmoVl for the last 4h by infusing em. Aand Bat mean rates of 156and 16Omgkg.h and at 10.55 f 0.18 and 11.22 _+0.27 mmoVl by infusing at 146 and 176 mg/kg.h, respectively. These differences in TG elimination rate were associated with a higher rise in PL which reached 4.87 mmoVl with em Avs 3.28 with em 8. It is interesting to note that the infusion rate had to be decreased with time (particularly when TG was clamped at 11 mmol/l), indicating a reduction in TG elimination. Since previous studies showed no change in the TG clearance from intact particles after repeated bolus injections, this phenomenon is likely due to a change in substrate, i.e. an increasing proportion of remnants. Indeed, after stopping infusions, TG decay from 11 mmoVl provided l/2 life values of 160 and 100 min with em. A and B, respectively. This suggests a stronger inhibitory effect of PL on TG elimination from remnants than from intact particles. In addition, measurements of individual FA and lipoprotein composition indicate that hypertriglyceridaemic clamp is also a powerful tool for kinetics studies on FA and lipoprotein metabolism.
0.2
Comparison of the effect of catheter insertion, sodium chloride infusion and ringer-acetate infusion in the rat K. Magnusson,K. Campos, E. Connolly andA. Wennberg V&urn fnsrirule for Human Nutrition, Stockholm, Sweden Since appropriate control treatment for parenteral nutrition experiments is often lacking, we investigated whether (1) catheter insertion, (2) NaCl versus Ringer-acetate or (3) infusion rate have any effect in the rat. 36 Male S.D. rats (aged 38d) were divided into 6 groups: (0-) unoperated; (Ot) catheter insertion into the vena cava but no infusion; two groups received Ringeracetate infusion at 180 (R180) and 360 (R360) ml/kg/day; two groups received sodium chloride (0.9%) at 180 (N18O) and 360 (N360) ml/kg/day. During the 28 day experiment all rats had access to standard diet and water. Results: Catheter insertion per se led to a decreased body wi gain/day (perhaps related to lower food intake) and a slight increase in spleen and kidney wts!kg body wt. Infusions led to a further decrease in body wi gaitiday, an increase in renal clearance of electrolytes but no change in plasma concentrations. Striktngly, infused rats also displayed a greater lung wl/kg body wl perhaps related to a retention of water. No differences were seen between Ringer andNaCI-infusions or infused volumes. It is concluded that catheter insertion and fluid infusion lead to significant changes in body growth and particularly lung wl in the rat. We recommend a salt infusion as the most suitable control for parenteral nutrition experiments but the choice between Ringer-acetate and saline is arbitrary.
CN
B
&WP
O0t Rl&l R3W Nl60 N360
e*nwq w 6.2?0.6
liwf
lcdnyspkn
Lune
3.54+0.07 25.1r2.4 34.0*2.0 7.22f0.2 2.26tO.17 52t0.4+ 22.9f1.4 33.5k2.3 7.57?0.6+ 2.64f0.36* 3.631'0.31 4.33io.46 2.45to.39 36?07" 201+1.6 31.Of2.0 7.7eo.3 4.09fff.ls" 4.6x75' 219_+17 32.0?1.9 7.79+0.5 232M.21' 7.67?0.5 2.35tO.55 4.15?0.33" 42?0.6 20.5rz.o 3i.MO.6 234tO.25 4.03+0.29' 47to.a 23.4kZ.l 32.1+1.1 7.63205 !mns_isD. + ~ef(ectofca~e~er;:"e(feclofnrtusrar(Pcoo5andoolresp.)
0.3 &rdiOv8sCui8r effects Of a high f8t and 8 hiah Garbohydrate meal: differences in peripheral and visceral bloodflOW MB. Siety, IA. Macdonald and L. Fullwood Departments of Physiolwy and Pharmacology and Medicine, University of Nottingham Medical School, Clifton Boulevard Nottingham, UK Ingestion of food may induce hypotension. This study investigates cardiovascular effects of high fat (F) or high carbohydrate (C)test meals. 10 healthy, subjects (4 female, mean Body Mass Index = 21 .6kg/m2, aged 22-35) were studied twice, before and after the ingestion of test meals containing 71% of the energy asfat, or 72% carbohydrate. Measurements of cardiac output (CO. Indirect Fick), calf BF (venous occlusion plethysmography) and mesenteric BF (Duplex Ultrasound), HR and BP along with arterial&d-venous blood glucose were made fasting and for the first 60 minutes postprandially. CO rose by approximately 1 Umin after tith meals. Calf BF rose slightly after the C meal, but fell within the first 15 minutes and remained low after the F meal (p < 0.03 ANOVA). 15 minutes after the C meal, mesenteric BF had increased by 135m!/min, and subsequently declined towards fasting levels. After the F meal, mesenteric BF rose progressively to a peak increase of 183mVmin at 45 mins (p < 0.05 ANOVA). HR increased by approximately 5 beats/min after each meal. There were no significant changes in BP. Blood glucose rose by 2.3mmol/l after C and O.Smmol/l after F (p < 0.05 ANOVA). Postprandial hypotension is not dependent upon changes in mesenteric BF but may result from limb vasodilatation. Mesenteric BF does not correspond to blood glucose levels.
0.4
Unliabilii
of biochemical parameters in the nutritional
assessment of patients undergoing allogeneic bone marrow transplantation (BMT)for leukemia M. Muscaritoli, M.C. Tirinde//i*, C. Cangiano, A. Cascino, F. Ceci: A.P. /ori’, A. Laviano, R. Strom’and F. Rossi Fanelli Ill Cepf. lntemal Medicine and ‘Dept. Human Biopathofogy, Universiify La Sapiehza, Rome, /ta/y The evaluation of nutritional state (NS) is still a matter of discussion. Anthropometric, biochemical and immunological parameters are often affected by non-nutritional factors depending on the underlying disease. Fever, sepsis, Graft-Versus-Host-Disease (GVHD) frequently occur in BMT patients, and blood transfusions and steroid therapy are often required. Ten patients (4 males, 6 females) undergoing BMT for acute and chronic myeloid or acute lymphoid leukemia were studied. On day t 1 after BMT, TPN via central vein was started (35 kcaVkg BW/day; 1.49 N/kg BW/day; 60% glucose, 40% lipids). Nutritional assessment was performed before (day 0) and after (day 15) TPN by means of anthropometric (BW, TSF, AMC), biochemical (Ceruloplasmin [Cer], C3c, Prealbumin [PAB], Transferrin (TRFj) and clinical (general well being, performance status [PSI, etc) parameters. Immunological parameters were obviously not employed. (Mean + SD):
hY0
Day15
;
l# lti
AMc (an)
FE&
UC @da
64.7r9.1 16.4t5.5 29.2k3.2 26.6+6.3 119*23 64.9t6.6 17.Of6.3 29.3e2.9 32.3r4.9 144f42 ~~d~vsdayO.:~
z*
TRF (mold0
24.7i6.1 274+47 16.9?61+ 197*34*
0.1
vmic
clamp: a new model for studying
MidYA. Cmpsnt& J. M. Kinney, VS. Siderova, M. Richelle, H. Nishitvaki, T. Olivecrone and R. J. Deckebaum Univ. tibre de Bruxeffes, Belgium Lipid infusions areoftenused for studying the metabolism of exogenous, but also endogenous hypertriglyceridaemia. Bolus injections allow to measure triglyceride (TG) elimination from intact particles. However, further catabolic steps lead to the formation of remnants removed at a slower rate by the liver. Hence, mixing of particles at different stage of catabolism occurs during lipid infusions, with a progressive enrichment in remnants. At the same time, lipid components are exchanged between exogenous particles and endogenous lipoproteins as well as cell membranes. Keeping plasma TG concentration stable during a prolonged period might offer a great advantage for studying the influence of lipid composition on these complex processes. In 6 voiunteers, endogenous lipid levels were stabilized after 3 h of combined glucose and aminoacids infusion (0.16 and 0.05g/kg.h, respectively). At that point, 2 10% lipid emulsions (em.) A and B, differing by their phospholipid (PL) content (12 and 69/l) were infused for the next 5 h. The proposed plasma levels of 6 and 11 mmol TG/I were reached after infusing both em. for 19 and 33 min at a primed rate of 1 g TGikg.h; infusion rates were then reduced and adjusted in relation to enzymatic determinations performed every E-15 min. TG levels were clamped at 6.14 + 0.13 and 5.81 + 0.16 mmoVl for the last 4h by infusing em. Aand Bat mean rates of 156and 16Omgkg.h and at 10.55 f 0.18 and 11.22 _+0.27 mmoVl by infusing at 146 and 176 mg/kg.h, respectively. These differences in TG elimination rate were associated with a higher rise in PL which reached 4.87 mmoVl with em Avs 3.28 with em 8. It is interesting to note that the infusion rate had to be decreased with time (particularly when TG was clamped at 11 mmol/l), indicating a reduction in TG elimination. Since previous studies showed no change in the TG clearance from intact particles after repeated bolus injections, this phenomenon is likely due to a change in substrate, i.e. an increasing proportion of remnants. Indeed, after stopping infusions, TG decay from 11 mmoVl provided l/2 life values of 160 and 100 min with em. A and B, respectively. This suggests a stronger inhibitory effect of PL on TG elimination from remnants than from intact particles. In addition, measurements of individual FA and lipoprotein composition indicate that hypertriglyceridaemic clamp is also a powerful tool for kinetics studies on FA and lipoprotein metabolism.
0.2
Comparison of the effect of catheter insertion, sodium chloride infusion and ringer-acetate infusion in the rat K. Magnusson,K. Campos, E. Connolly andA. Wennberg V&urn fnsrirule for Human Nutrition, Stockholm, Sweden Since appropriate control treatment for parenteral nutrition experiments is often lacking, we investigated whether (1) catheter insertion, (2) NaCl versus Ringer-acetate or (3) infusion rate have any effect in the rat. 36 Male S.D. rats (aged 38d) were divided into 6 groups: (0-) unoperated; (Ot) catheter insertion into the vena cava but no infusion; two groups received Ringeracetate infusion at 180 (R180) and 360 (R360) ml/kg/day; two groups received sodium chloride (0.9%) at 180 (N18O) and 360 (N360) ml/kg/day. During the 28 day experiment all rats had access to standard diet and water. Results: Catheter insertion per se led to a decreased body wi gain/day (perhaps related to lower food intake) and a slight increase in spleen and kidney wts!kg body wt. Infusions led to a further decrease in body wi gaitiday, an increase in renal clearance of electrolytes but no change in plasma concentrations. Striktngly, infused rats also displayed a greater lung wl/kg body wl perhaps related to a retention of water. No differences were seen between Ringer andNaCI-infusions or infused volumes. It is concluded that catheter insertion and fluid infusion lead to significant changes in body growth and particularly lung wl in the rat. We recommend a salt infusion as the most suitable control for parenteral nutrition experiments but the choice between Ringer-acetate and saline is arbitrary.
CN
B
&WP
O0t Rl&l R3W Nl60 N360
e*nwq w 6.2?0.6
liwf
lcdnyspkn
Lune
3.54+0.07 25.1r2.4 34.0*2.0 7.22f0.2 2.26tO.17 52t0.4+ 22.9f1.4 33.5k2.3 7.57?0.6+ 2.64f0.36* 3.631'0.31 4.33io.46 2.45to.39 36?07" 201+1.6 31.Of2.0 7.7eo.3 4.09fff.ls" 4.6x75' 219_+17 32.0?1.9 7.79+0.5 232M.21' 7.67?0.5 2.35tO.55 4.15?0.33" 42?0.6 20.5rz.o 3i.MO.6 234tO.25 4.03+0.29' 47to.a 23.4kZ.l 32.1+1.1 7.63205 !mns_isD. + ~ef(ectofca~e~er;:"e(feclofnrtusrar(Pcoo5andoolresp.)
0.3 &rdiOv8sCui8r effects Of a high f8t and 8 hiah Garbohydrate meal: differences in peripheral and visceral bloodflOW MB. Siety, IA. Macdonald and L. Fullwood Departments of Physiolwy and Pharmacology and Medicine, University of Nottingham Medical School, Clifton Boulevard Nottingham, UK Ingestion of food may induce hypotension. This study investigates cardiovascular effects of high fat (F) or high carbohydrate (C)test meals. 10 healthy, subjects (4 female, mean Body Mass Index = 21 .6kg/m2, aged 22-35) were studied twice, before and after the ingestion of test meals containing 71% of the energy asfat, or 72% carbohydrate. Measurements of cardiac output (CO. Indirect Fick), calf BF (venous occlusion plethysmography) and mesenteric BF (Duplex Ultrasound), HR and BP along with arterial&d-venous blood glucose were made fasting and for the first 60 minutes postprandially. CO rose by approximately 1 Umin after tith meals. Calf BF rose slightly after the C meal, but fell within the first 15 minutes and remained low after the F meal (p < 0.03 ANOVA). 15 minutes after the C meal, mesenteric BF had increased by 135m!/min, and subsequently declined towards fasting levels. After the F meal, mesenteric BF rose progressively to a peak increase of 183mVmin at 45 mins (p < 0.05 ANOVA). HR increased by approximately 5 beats/min after each meal. There were no significant changes in BP. Blood glucose rose by 2.3mmol/l after C and O.Smmol/l after F (p < 0.05 ANOVA). Postprandial hypotension is not dependent upon changes in mesenteric BF but may result from limb vasodilatation. Mesenteric BF does not correspond to blood glucose levels.
0.4
Unliabilii
of biochemical parameters in the nutritional
assessment of patients undergoing allogeneic bone marrow transplantation (BMT)for leukemia M. Muscaritoli, M.C. Tirinde//i*, C. Cangiano, A. Cascino, F. Ceci: A.P. /ori’, A. Laviano, R. Strom’and F. Rossi Fanelli Ill Cepf. lntemal Medicine and ‘Dept. Human Biopathofogy, Universiify La Sapiehza, Rome, /ta/y The evaluation of nutritional state (NS) is still a matter of discussion. Anthropometric, biochemical and immunological parameters are often affected by non-nutritional factors depending on the underlying disease. Fever, sepsis, Graft-Versus-Host-Disease (GVHD) frequently occur in BMT patients, and blood transfusions and steroid therapy are often required. Ten patients (4 males, 6 females) undergoing BMT for acute and chronic myeloid or acute lymphoid leukemia were studied. On day t 1 after BMT, TPN via central vein was started (35 kcaVkg BW/day; 1.49 N/kg BW/day; 60% glucose, 40% lipids). Nutritional assessment was performed before (day 0) and after (day 15) TPN by means of anthropometric (BW, TSF, AMC), biochemical (Ceruloplasmin [Cer], C3c, Prealbumin [PAB], Transferrin (TRFj) and clinical (general well being, performance status [PSI, etc) parameters. Immunological parameters were obviously not employed. (Mean + SD):
hY0
Day15
;
l# lti
AMc (an)
FE&
UC @da
64.7r9.1 16.4t5.5 29.2k3.2 26.6+6.3 119*23 64.9t6.6 17.Of6.3 29.3e2.9 32.3r4.9 144f42 ~~d~vsdayO.:~
z*
TRF (mold0
24.7i6.1 274+47 16.9?61+ 197*34*