Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves

Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n = 4) or GLP-2 (100 μg/kg BW per day bovine GLP-2 in bovine serum albumin; n = 4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 μg/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, β-hydroxybutyrate and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U¹³-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, concurrent with stimulated growth of the small intestinal epithelium in post-absorptive ruminant calves.     

Starvation-induced changes in metabolic rate, blood flow, and regional energy expenditure in rats

Starvation results in an energy-conserving reduction in metabolic rate that has features of an adaptive response. Tissue and organ sites of this response were investigated by examining the effects of starvation for 5 d on tissue blood flow (microsphere method) and regional arteriovenous O2 differences ((a-v)O2) in conscious rats resting quietly at 28 degrees C. Comparison was with fed and overnight-fasted animals. Whole body resting metabolic rates (MR), colonic temperatures (Tc), and tissue weights were also determined. Quantitative changes in energy expenditure (as O2 consumption) were obtained for two regions: the portal-drained viscera (PDV) and the hindquarters (HQ). Fasting overnight resulted in increased blood flow to white adipose tissue (WAT) and decreased flow to the brain, PDV, testes, and skin; however, MR, Tc, the two regional ((a-v)O2, and the weights of most tissues were not significantly altered. In comparison with overnight fasting, starvation for 5 d resulted in a 13% reduction in body weight, weight loss in many tissues and organs, a 26% reduction in MR, a decline of 0.5 degree C in Tc, decreased (a-v)O2 across both the PDV and HQ, reduced cardiac output, and decreased blood flow to the heart, PDV, skin, WAT, leg muscle, HQ, and the musculoskeletal body as a whole. Utilization of O2 by the PDV and HQ (flow X (a-v)O2) declined by amounts that accounted for 22 and 18%, respectively, of the reduction in MR. The reductions in cardiac output (18%) and heart blood flow (36%) indicate that the heart also made a contribution to energy conservation (roughly estimated as 5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of erythrocytes and plasma in threonine and lysine transfer across the portal drained viscera and the liver in pigs. Effect of threonine and lysine dietary supply

Contributions of erythrocytes and plasma to threonine and lysine transport across the PDV and the liver were determined in growing pigs successively fed a threonine deficient diet and a control well-balanced diet (experiment 1) or a lysine deficient or a well-balanced diet (experiment 2). The animals were surgically prepared for insertion of chronic catheters in the mesenteric vein (MV), the portal vein (PV), a hepatic vein (HV) and the carotid artery (CA). Plasma and whole blood AA concentrations in PV, HV and CA and PV and HV blood flows were determined during 6 hours of para-aminohippuric acid constant infusion. During this period the pigs were continuously fed (1 meal per hour). The contribution of plasma to lysine and threonine transport was higher in pigs fed the well balanced diets. More than 50% of threonine and lysine appearing in the PV and in the HV are transported by the plasma. Our results suggest that erythrocytes are probably little involved in lysine and threonine transfer across the liver and digestive tract of pig continuously fed.     

Amino acid gradients across the intestinal circulation in fetal lambs.

Amino acids, including glutamine, glutamate and asparagine are major metabolic substrates for the adult enterocyte of several species. To determine whether circulating amino acids are utilized by the fetal intestine, we studied nine fetal sheep (mean gestational age 128 +/- 5 days; term: 147 days). Catheters were inserted into the descending aorta (DA) and the mesenteric vein (MV) to allow for simultaneous blood sampling across the intestine. Fetal blood gas, haemoglobin; O2 saturation and O2 tension were measured. Ammonia was determined by an enzymatic method and HPLC analysis was used to measure the content of all amino acids in DA (descending aorta) and MV (mesenteric vein). Intestinal blood flow measurements were obtained using the radionuclide microsphere method. Intestinal blood flow (81 +/- 28 ml/min/100g) and arterial pH (7.37 +/- 0.04) were within normal range for unstressed fetal lambs. Glutamine and glutamate were the only amino acids that were significantly taken up across the fetal intestinal circulation. The fetal intestine extracted approximately 21% of the delivered glutamine (6.8 +/- 4.5 mumol/min/100g), 7% of the delivered glutamate (1.3 +/- 1.1 mumol/min/100g) and 2.7% of the delivered oxygen (43.0 +/- 19.1 mumol/min/100g). These data suggest that glutamine and glutamate are major substrates for the intestine in unstressed fetal lambs.     

Plasma kinetics and matrix residues of deoxynivalenol (DON) and zearalenone (ZEN) are altered in endotoxaemic pigs independent of LPS entry site

This study aimed to investigate a potential modulatory effect of E. coli lipopolysaccharide (LPS) on the kinetics of deoxynivalenol (DON) and zearalenone (ZEN) after pre- or post-hepatic LPS administration to unravel the putative role of the liver. Fifteen barrows were fed a diet containing mycotoxin-contaminated maize (4.59 mg DON/kg feed, 0.22 mg ZEN/kg feed) for 29 days and equipped with pre-hepatic catheters (portal vein, “po”) and post-hepatic catheters (jugular vein, “ju”), facilitating simultaneous infusion of LPS (“LPS group”, 7.5 μg/kg body weight) or 0.9% sterile NaCl solution (control, “CON group”, equivolumar to LPS group) and blood sampling. This resulted in three infusion groups, depending on infusion site: CON_ju-CON_po, CON_ju-LPS_po, and LPS_ju-CON_po. On day 29, pigs were fed their morning ration (700 g/pig) (?15 min), and blood samples were collected at regular intervals relative to infusion start. At 195 min, pigs were sacrificed and bile, urine, liquor, and liver samples collected. DON concentrations in jugular and portal blood decreased in both LPS-infused groups, whereas the ZEN concentrations increased, regardless of the treatment site. In liver tissue, a decrease of both toxin concentrations was observed in endotoxaemic pigs as well as a drop in hepatic conjugation, regardless of LPS entry site. In contrast to our hypothesis, DON and ZEN were not differently altered depending on the LPS-entry site. Neither the absorption nor the accumulation of DON and ZEN in different tissues differed significantly between animals which were infused with LPS via either the jugular or portal vein.     

Comparison of organ uptake and disappearance half-time of human epidermal growth factor and insulin

Epidermal growth factor (EGF), which was originally identified in salivary glands and saliva, has been also found in the kidney and urine, suggesting that the kidney may be an alternate source of this peptide. Liver was considered as the major site of the degradation of EGF but the involvement of other organs has been little studied. Therefore, we carried out comparative studies on the organ uptake and the disappearance half-time of EGF and insulin (having similar molecular size) in the same model of anesthetized dog with arterial (from aorta) and venous (from mesenteric, portal, hepatic, renal, femoral and jugular veins) blood sampling from various organs. Basal plasma level of EGF (1.32 +/- 0.33 pmol/l) and insulin (62.1 +/- 13.8 pmol/l) in the aorta was not significantly different from that recorded at various sampling sites. During i.v. infusion of EGF at 41.6 and 166.6 pmol/kg/h, the respective arterial EGF concentrations averaged 103 +/- 21 and 240 +/- 49 pmol/kg/h and the percent reduction in plasma EGF after passage through the head, leg, intestines and liver was about 30-50% and that after passage through the kidney was about 95%. During insulin (6.9 pmol/kg/h) infusion, the arterial hormone level averaged 227 +/- 21 pmol/l and this level was significantly reduced (by 23-42%) after passage through the head, leg, intestine, liver and kidney but no significant difference was found between various venous sampling sites. EGF and insulin appearing in the urine during EGF or insulin infusion accounted for about 40 and 7% of the difference between the entering and leaving renal masses of the peptide. Mean disappearance half time on stopping of EGF and insulin infusion was, respectively, 2.32 +/- 0.58 and 6.88 +/- 1.25 min. We conclude that unlike insulin, which is removed to similar extent by various organs including the kidney and the liver, EGF is taken up mainly by kidney and EGF present in urine originates mainly from renal clearance of peptide.     

Interorgan ammonia, glutamate, and glutamine trafficking in pigs with acute liver failure

Ammonia reduction is the target for therapy of hepatic encephalopathy, but lack of quantitative data about how the individual organs handle ammonia limits our ability to develop novel therapeutic strategies. The study aims were to evaluate interorgan ammonia metabolism quantitatively in a devascularized pig model of acute liver failure (ALF). Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind leg, and lungs in ALF pigs. ALF pigs developed hyperammonemia and increased glutamine levels, whereas glutamate levels were decreased. PDV contributed to the hyperammonemic state mainly through increased shunting and not as a result of increased glutamine breakdown. The kidneys were quantitatively as important as PDV in systemic ammonia release, whereas muscle took up ammonia. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Our study provides new data supporting the concept of glutamate deficiency in a pig model of ALF. Furthermore, the kidneys are quantitatively as important as PDV in ammonia production, and the muscles play an important role in ammonia removal.     

Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice

Hypoglycemia-induced counterregulatory failure is a dangerous complication of insulin use in diabetes mellitus. Controlled hypoglycemia studies in gene knockout models, which require the use of mice, would aid in identifying causes of defective counterregulation. Because stress can influence counterregulatory hormones and glucose homeostasis, we developed glucose clamps with remote blood sampling in conscious, unrestrained mice. Male C57BL/6 mice implanted with indwelling carotid artery and jugular vein catheters were subjected to 2 h of hyperinsulinemic glucose clamps 24 h apart, with a 6-h fast before each clamp. On day 1, blood glucose was maintained (euglycemia, 178 +/- 4 mg/dl) or decreased to 62 +/- 1 mg/dl (hypoglycemia) by insulin (20 mU x kg(-1) x min(-1)) and variable glucose infusion. Donor blood was continuously infused to replace blood sample volume. Baseline plasma epinephrine (32 +/- 8 pg/ml), corticosterone (16.1 +/- 1.8 microg/dl), and glucagon (35 +/- 3 pg/ml) were unchanged during euglycemia but increased significantly during hypoglycemia, with a glycemic threshold of approximately 80 mg/dl. On day 2, all mice underwent a hypoglycemic clamp (blood glucose, 64 +/- 1 mg/dl). Compared with mice that were euglycemic on day 1, previously hypoglycemic mice had significantly higher glucose requirements and significantly lower plasma glucagon and corticosterone (n = 6/group) on day 2. Epinephrine tended to decrease, although not significantly, in repeatedly hypoglycemic mice. Pre- and post-clamp insulin levels were similar between groups. We conclude that counterregulatory responses to acute and repeated hypoglycemia in unrestrained, chronically cannulated mice reproduce aspects of counterregulation in humans, and that repeated hypoglycemia in mice is a useful model of counterregulatory failure.     

Route of administration (enteral or parenteral) affects the contribution of L-glutamine to de novo L-arginine synthesis in mice: a stable-isotope study

A pathway from enteral L-glutamine as substrate for L-arginine synthesis is suggested by previous studies. L-Glutamine and L-glutamine dipeptides exhibit numerous beneficial effects in experimental and clinical studies. In trauma patients, enteral L-glutamine supply increased plasma L-arginine. The present study was designed to quantify the contribution of L-glutamine to the de novo L-citrulline and L-arginine synthesis in mice when L-glutamine is administered in a high dose of labeled L-glutamine or L-alanyl-L-glutamine by the enteral or parenteral route. For this purpose, male Swiss mice (n = 43) underwent a laparotomy, and catheters were inserted for sampling and infusion. A primed, constant, and continuous infusion of L-alanyl-L-[2-(15)N]glutamine (dipeptide groups) or L-[2-(15)N]glutamine (free L-glutamine groups), simultaneously with L-[ureido-(13)C,(2)H(2)]citrulline and L-[guanidino-(15)N(2),(2)H(2)]arginine, was given (steady-state model). Mice received the L-glutamine tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by LC-MS. Arterial L-glutamine concentrations were the highest in the intravenous dipeptide group. L-Glutamine was converted to L-citrulline and L-arginine when L-[2-(15)N]glutamine and L-alanyl-L-[2-(15)N]glutamine were given by enteral or parenteral route. The contribution of L-glutamine to the de novo synthesis of L-citrulline and L-arginine was higher in the enteral groups when compared with the intravenous groups (P < 0.005). Therefore, the route of administration (enteral or parenteral) affects the contribution of L-glutamine, provided as free molecule or dipeptide, to the de novo synthesis of L-arginine in mice.     

Renal vein outflow recording in rats and rabbits: alternative method of R.B.F. measurement

A method is described for continuous measurement of total renal blood flow in anesthetized rats and rabbits. It consists of recording time intervals in which a fixed volume of renal vein outflow enters into an extracorporeal renin vein - jugular vein shunt and is pumped back to animals' circulation. This technique yields absolute flow values of unequalled accuracy and requires virtually no calibration; however, it is not suitable for recording rapid flow transients. The RBF measured averaged 5.5 +/- (SE) 0.1 ml/min.g kidney weight in rats and 2.5 +/- 1.1 ml/min.g in rabbits; the flow was stable over at least 1.5-2 hrs. The rat kidneys tested showed usual capacity to autoregulate blood flow during graded reduction in renal perfusion pressure.     

Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats.

It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275-300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30- to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg. kg(-1). min(-1)) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 +/- 2, 33 +/- 2, and 30 +/- 2 pg/ml and 1.34 +/- 0.08, 1. 37 +/- 0.18, and 1.66 +/- 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 +/- 4 mg/dl for Po, 220 +/- 3 for Pe low, and 255 +/- 2 for Pe high group. The liver glycogen content (micromol glucose/g liver) in the two Pe groups was not statistically different (51 +/- 7 and 65 +/- 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 +/- 9, P < 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species.     

The analysis of glucose kinetics using a single jugular catheter in awake rats

The rates of glucose production and utilization can be estimated by a primed-constant infusion technique using separate catheters for the infusion of radiolabelled glucose and periodic blood withdrawal. In rats, a carotid artery catheter is most often combined with a jugular or femoral venous catheter in such studies. We presently describe a method which utilizes a single jugular catheter for both infusion and sampling in the awake rat. This method is directly compared with simultaneous carotid artery sampling during both the dynamic steady state and a nonsteady state induced by a constant infusion of insulin. Our results demonstrate the validity of a single vein design for the analysis of glucose kinetics in either state. Rapid sampling and complete flushing prevent disruption of infusate equilibrium and sample contamination respectively. This single catheter method requires less technical skill for placement, reduces surgical intervention and enhances the comfort of the awake rat.     

The depressive action of ammonium chloride on the hepatic blood flow in sheep

Using the 133Xe clearance method it is shown that NH4Cl infusion into the anterior mesenteric vein decreased capillary blood flow in the liver. Phentolamine completely and propranolol partially prevented the depressive action of NH4Cl on hepatic blood flow. NH5Cl infused into the jugular vein provoked a slight increase in the hepatic blood flow. The adrenaline-like action of ammonium ion on the blood circulation in the liver region is discussed.     

Chronic instrumentation and longterm investigation in the fetal and maternal baboon: tether system, conditioning procedures and surgical techniques

A tether system, conditioning procedures and surgical techniques were designed to maintain chronic catheters and electrodes in the pregnant baboon and her fetus. The tether system was comprised of a lightweight metal backpack containing catheters and electrodes, couplers, pressure transducers and electrical cabling. The backpack was held snugly in place by shoulder and body straps. A flexible metal tether connected the pack to a ball bearing assembly mounted on the top of the animal's home cage. Attached to the assembly were two infusion pumps, fluid reservoir and slip ring electrical connector. The entire system rotated freely with the movements of the animal; thus, the instrumentation and connectors were secure while access was maintained for continuous physiologic recording and intravascular infusion or intermittent blood sampling with minimal physical restraint. Animals were conditioned to accept the system prior to pregnancy and animals who demonstrated tolerance were bred. An initial group of 10 pregnant animals were sham tethered during pregnancy at 102 +/- 7 days with term gestation estimated at 180 days. Surgical procedures were done at 136 +/- 4 days with placement of catheters in the maternal femoral artery and vein, fetal carotid artery jugular vein and trachea, amniotic fluid cavity, and electrodes for fetal electrocardiogram and electroencephalogram. The mean fetal survival time was 9.3 (range 0 to 29) days. The major complications which led to early delivery were placental abruption and rupture of amniotic membranes. With ultrasonic localization of the placenta and determination of fetal position before surgery, these complications may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)     

A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates

A jacket and tethering system was used to maintain chronic catheters in monkeys, which provided catheter access and manipulability without further restraint. Surgical placement of catheters and a temperature probe allowed for a common cutaneous exit and interface with the jacket and tether. Monkeys were fitted in a sterile leather or denim jacket which was attached to a sterilized flexible stainless steel cable. Through this conduit, an indwelling temperature probe, as well as catheters from the internal jugular and femoral veins, were attached to a swivel unit located on the upper portion of the cage. The internal jugular catheter was used for the continuous infusion of support solution. The catheter from the femoral vein was maintained with a heparin lock and used for serial blood sampling. Using this system, it was possible to obtain frequent blood samples and body temperature readings, and to administer a continuous intravenous infusion without chemical or excessive physical restraint. To date, 367 monkeys, 322 cynomolgus (Macaca fasicularis), 16 rhesus (Macaca mulatta), and 21 African green (Cercopithecus aethiops) have been studied using this procedure.     

Postprandial intestinal and whole body nitrogen kinetics and distribution in piglets fed a single meal

Our aim was to characterize the postprandial total and dietary N fluxes in the portal drained viscera (PDV) and whole body after administration of a single meal in young pigs. Seven 4-wk-old piglets, implanted with a portal flow probe and portal, arterial and venous catheters, received a primed constant [(18)O]urea intravenous infusion and were studied for 8 h after a bolus mixed meal ingestion (46 mmol N/kg body wt) intrinsically labeled with (15)N to trace dietary N fluxes. The real cecal digestibility of the formula was 94.3% (SD 1.8). PDV output of dietary N was found principally in the pool of circulating protein (51% of the measured dietary N PDV output), in the free alpha-amino N pool (44%), and to a lesser extent in ammonia (5%). Dietary N release in alpha-amino N and ammonia mainly occurred during the first 3 h. Total and exogenous postprandial urea productions were 5.8 and 2.0 mmol N/kg body wt, respectively. At the end of the postprandial period, losses of dietary N amounted to 10.3% of the dose: 5.7% through ileal losses and 4.6% by deamination and transfer to urea. Net postprandial retention of dietary N was 90.4% (SD 1.3), of which 20% was found in splanchnic zone (small intestine 10%, liver 5%, and plasma protein 3%) and 42% in peripheral zone (muscle 31%, skin 6%). In conclusion, our results show a high efficiency of dietary N utilization for muscular uptake and anabolic utilization. However, the results obtained point out the necessity to further explore the form of dietary N released into the portal blood.     

Somatotropin-induced protein anabolism in hindquarters and portal-drained viscera of growing pigs

To differentiate the effect of somatotropin (ST) treatment on protein metabolism in the hindquarter (HQ) and portal-drained viscera (PDV), growing swine (n = 20) treated with ST (0 or 150 microg x kg(-1) x day(-1)) for 7 days were infused intravenously with NaH(13)CO(3) and [(2)H(5)]phenylalanine and enterally with [1-(13)C]phenylalanine while in the fed state. Arterial, portal venous, and vena cava whole blood samples, breath samples, and blood flow measurements were obtained for determination of tissue and whole body phenylalanine kinetics under steady-state conditions. In the fed state, ST treatment decreased whole body phenylalanine flux, oxidation, and protein degradation without altering protein synthesis, resulting in an improvement in whole body net protein balance. Blood flow to the HQ (+80%), but not to the PDV, was increased with ST treatment. In the HQ and PDV, ST increased phenylalanine uptake (+44 and +23%, respectively) and protein synthesis (+43 and +41%, respectively), with no effect on protein degradation. In ST-treated and control pigs, phenylalanine was oxidized in the PDV (34-43% of enteral and arterial sources) but not the HQ. In both treatment groups, dietary (40%) rather than arterial (10%) extraction of phenylalanine predominated in gut amino acid metabolism, whereas localized blood flow influenced HQ amino acid metabolism. The results indicate that ST increases protein anabolism in young, growing swine by increasing protein synthesis in the HQ and PDV, with no effect on protein degradation. Differing results between the whole body and the HQ and PDV suggest that the effect of ST treatment on protein metabolism is tissue specific.     

Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity

The plasma concentration of the dopamine (DA) metabolite, homovanillic acid (HVA), is used as an indicator of central nervous system dopaminergic activity. Using percutaneously inserted catheters we were able to obtain blood samples simultaneously from the right and left internal jugular veins. Veno-arterial HVA plasma concentration differences combined with adjusted organ plasma flows were used, according to the Fick Principle, to determine the HVA overflow from the brain. The HVA overflow from the liver was also measured. HVA overflow from the brain represented 12% of the total body HVA production. A similar amount was released from the liver, illustrating the limited validity of peripheral plasma HVA measurements as an indicator of central dopaminergic activity. HVA release from the human brain displayed a degree of asymmetry, the overflow into the left internal jugular vein being 36% greater than that into the right. Cerebral venous blood flow scans indicated that cortical cerebral regions drained preferentially into the right internal jugular; by inference the higher HVA overflow on the left originated from dopamine-rich subcortical brain areas. Since HVA in plasma may arise from the metabolism of DA existing either as a neurotransmitter or a norepinephrine (NE) precursor we measured the internal jugular vein plasma concentrations of NE, and its metabolite dihydroxyphenylglycol (DHPG), to determine whether they displayed a similar pattern of release to HVA. The overflow of both NE and DHPG into the right internal jugular vein was approximately double that on the left. Since the overflow of HVA did not parallel that of NE and DHPG it may be inferred that the origin of much of the subcortically produced HVA is from dopaminergic neurons and not from the metabolism of precursor DA in noradrenergic neurones or cerebrovascular sympathetic nerves.     

The effect of jugular or abomasal infusion of amino acids on milk yield in lactating cows fed a protein deficient diet

The influence of first-pass splanchnic metabolism was investigated by comparing the response of 5 lactating cows to an infusion of an amino acid mixture into the abomasum or a jugular vein over 5 d according to a complete block design. The basal diet and the amino acid infusion provided 71% and 14% of crude protein requirements, respectively. The jugular infusion increased (P = 0.01) milk yield by 0.80 kg in comparison to the abomasal infusion, but milk protein yield was not altered. The jugular infusion tended to increase (P = 0.06) the arterial concentration of total essential amino acids by 11% relatively to the abomasal infusion. Mammary plasma flow and net fluxes of amino acids and glucose were not affected by the infusion sites. Variations in essential amino acid concentrations suggest that splanchnic metabolism alters peripheral delivery of amino acids but the recirculation of amino acids within the animal decreased the impact of the first-pass splanchnic metabolism on lactational performances.     

Whole blood and plasma amino acid transfers across the portal drained viscera and liver of the pig.

Whole blood (WB) and plasma (P) amino acid transfers across the portal drained viscera and the liver were determined during 6 h of a constant p-aminohippuric acid infusion in three hourly-fed Landrace x Large-White pigs (30.5 kg, mean live weight) surgically prepared with chronically inserted catheters in a mesenteric vein (MV), the portal vein (PV), an hepatic vein (HV) and the carotid artery (CA). Plasma and WB amino acid concentrations were determined in the CA, PV and HV. The plasma/WB ratios showed no significant differences for vessels except for lysine and glutamate for which this ratio is significantly higher in the HV and in the PV for lysine. This suggests that the PV lysine and HV glutamate were preferentially transported in the plasma. In the PV, threonine, valine and alanine are transported by both plasma and red blood cells. These data show that the contribution of plasma and whole blood to amino acid transport can be different between amino acids and between individual tissues.