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Lactic acid infusion in dogs: effects of varying infusate pH.

This study had two purposes: 1) to determine the effects of varying the pH of lactic acid infusion solutions on the acid-base status of anesthetized dogs, and 2) to determine the effect of elevated blood lactate concentration on muscle lactate concentration. The experiments were performed on the in situ gastro cnemius-plantaris muscle group in 14 mongrel dogs. The infusions increased the arterial blood lactate concentration to 11.0 +/- 0.5 (SE) mM after 20 min. Above an infusate pH of 4.4, the arterial pH increased by 0.118-0.167 during infusion; the arterial pH was unchanged when the infusate pH was between 3.4 and 4.0; and the arterial pH decreased as infusate pH decreased below 3.0. The effect of lactic acid infusion on blood pH appears to be the result of two opposing effects: 1) an acidifying effect due to its weak acid properties, and 2) an alkalinizing effect due to the metabolism of sodium lactate. The estimated ratio between intracellular muscle lactate and venous plasma water lactate averaged 0.647 +/- 0.038, indicative of a substantial gradient between blood and muscle. The infusion produced a significant change from lactate output to lactate uptake by the muscles. The infusion also transiently increased muscle blood flow and oxygen uptake.

Acid-Base Equilibrium↗

Protein-sparing effect of substrate infusion in surgical patients is governed by the clinical state, and not by the individual substrate infused.

We have determined iostopically the effect of either glucose or lipid infusion on rates of glucose turnover, glucose oxidation, and net protein catabolism (NPC) in three groups of surgical patients. Kinetic measurements were performed using the primed constant infusion of 3H-glucose, and either 14C-glucose or 14C-urea. The three groups included patients with: (1) sepsis and/or trauma (ST); (2) upper gastrointestinal cancer (UGI); (3) lower gastrointestinal cancer (LGI). In each patient group the effect of either glucose infusion (approximately 4 mg/kg.min) or lipid infusion (20% Intralipid lipid emulsion infused to provide calories approximately isocaloric to the glucose infusion) was assessed. The infusion of calories as either glucose or lipid was equally effective as a means of suppressing NPC in each individual patient group, and the degree of response was governed by the clinical disease state. In the LGI and ST patients the infusion of either glucose or fat resulted in a significant suppression of NPC (p less than 0.005) of approximately 15%. However, the ongoing rate of NPC that occurred despite substrate infusion was more than twice as great in the ST patients as in the LGI patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.

Adult↗

Controlled ruminal infusion of sodium bicarbonate. 3. Influence of infusion dose on systemic acid-base status, minerals, and ruminal milieu.

Four ruminally cannulated, lactating Holstein cows were assigned to a 4 x 4 Latin square to monitor effects of intraruminal NaHCO3 infusion on temporal changes in ruminal and systemic acid-base status and mineral metabolism. Twice daily from 2 to 4 h postfeeding, cows were infused with 0, 110, 220, or 330 g of NaHCO3 dissolved in 3.8 L of water. All cows had access to their TMR of sorghum silage and concentrate (35: 65, DM basis) for 2 h twice daily. Ruminal fluid, blood, and urine were collected at feeding and every 30 min postfeeding for 12 h on the last day of each 14-d period. Total urine volume also was measured during this interval. Infusion of buffer increased ruminal fluid buffering capacity transiently at 4.5 h postfeeding but otherwise did not markedly affect ruminal fluid acid-base status. Systemic acid-base status was unaffected by the buffer primarily because renal excretion of base successfully reduced systemic base load. Urine volume increased in response to NaHCO3 infusion. Buffer infusion increased urinary excretion of Na, Mg, and K but decreased Ca excretion for 12 h postfeeding; Cl excretion was not affected. Buffer infusion tended to increase total VFA in ruminal fluid. Our data indicate that homeostatic mechanisms can eliminate exogenous base via the kidneys; hence, acid-base status was not perturbed by infusion of NaHCO3. The increased excretion of Mg and K with buffer infusion indicates that the dietary requirements for these minerals may be increased by NaHCO3. Although loss of Ca through the urine was reduced by buffer infusion, this reduction may indicate reduced availability of Ca to the cow. The diuresis accompanying large doses of NaHCO3 may increase dietary requirements for some minerals.

Acid-Base Equilibrium↗

Decrease in cochlear blood flow with infusion of nitric oxide synthase inhibitor and its recovery with L-arginine infusion: comparison with abdominal blood flow and auricular blood flow.

We observed changes in cochlear blood flow (CoBF), abdominal blood flow (AbBF) and auricular blood flow (AuBF) in rats after administration of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME). Ten min after i.v. infusion of L-NAME, L-arginine, a substrate of NO, was infused (100 mg/kg) intravenously. Using a laser Doppler flowmeter, changes in blood flow were recorded from the basal turn of the right cochlea, abdominal wall or right auricle, and systemic blood pressure (BP) was recorded simultaneously from the left femoral artery. As another parameter of vascular response, vascular conductance (VC) was calculated from blood flow/mean BP. I.v. infusion of L-NAME produced a dose-dependent depression of cochlear VC at concentrations of 0.2 (-18.9%), 1 (-37.9%), 5 (-45.8%) and 10 mg/kg (-48.3%). Infusion of L-arginine partially reversed the decrease of CoBF caused by L-NAME. The group that received a 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery (23.8%) with L-arginine, while the 10 mg/kg group showed the smallest degree of recovery (10.1%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% depression of VC) and with no significance compared to the decrease in CoBF (5 mg/kg L-NAME). Likewise, AuBF showed a decrease (-44.0% depression of VC) after infusion of L-NAME (10 mg/kg), the decrease being less than that of CoBF (10 mg/kg L-NAME). Recoveries from these decreased levels of VC in the AbBF and AuBF groups appeared to be smaller than those in the CoBF groups at the same dose of L-NAME (5.5% vs 17.3% in abdominal VC; 5.3% vs 10.1% in auricular VC). In a previous study comparing the CoBF changes caused by i.v. infusion and round window application of L-NAME, we proposed that i.v. infusion of L-NAME in rats primarily affects the precapillary arteriole of the spiral modiolar artery, which effectively regulates cochlear microcirculation as a resistance artery. Thus we assume that there may exist an active pathway of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate system in the above vessels. With regard to the finding of a smaller recovery of VC with L-arginine in both the AbBF and AuBF groups, we consider that differences in L-arginine availability or uptake, and in the synthesis of NO, may exist between the cochlear and cutaneous vasculatures.

Abdominal Wall↗

Calculation of a gallbladder ejection fraction: advantage of continuous sincalide infusion over the three-minute infusion method.

The purpose of this study was to investigate alternative methods of infusing sincalide for calculation of a gallbladder ejection fraction (GBEF) during cholescintigraphy (5 mCi 99mTc-mebrofenin). After gallbladder filling, three methods of infusion were compared in 23 normal volunteers: (1) 0.02 microgram/kg as a 3-min infusion, (2) 0.02 microgram/kg as a 30-min infusion, and (3) 0.01 microgram/kg as a 30-min infusion (14 subjects), all performed on separate days. With the 3-min infusion, the emptying pattern was usually exponential and completed in 15 min. The mean (GBEF) was 52% +/- 26% at 20 min and 56% +/- 27% at 30 min (range 0%-100%). GBEFs were less than 35% in six subjects and 35%-38% in four. Side effects were noted by 11/23 subjects. With the slow infusions, emptying was linear; no side effects were noted. With 0.02 microgram/kg, the mean GBEF was 50% +/- 27% at 20 min and 70% +/- 22% at 30 min (range 26%-95%). Similar results were seen with 0.01 microgram/kg, but the data were more limited. The 30-min infusion had a higher normalcy rate than the 3-min method (91% versus 74%). Females had significantly lower GBEFs than males (p less than 0.05%). We conclude that the slow infusion method is preferable; it is more physiological, results in more complete emptying, has no side effects, has less normal variability, and should improve the specificity of this test. The lower mean female GBEF may have pathophysiological significance.

Adult↗

Fibrinolytic treatment with ultra-high streptokinase infusion via the dorsalis pedis vein offers no advantage over systemic infusion via the brachial vein in patients with deep vein thrombosis of the leg.

The present study into the fibrinolytic therapy of deep vein thrombosis (DVT) considers whether streptokinase infusion into the dorsalis pedis vein of the affected leg (ipsipedal infusion) yields higher lysis rates than systemic infusion via the brachial vein (systemic infusion). In both cases the dosage regimen selected was a short-term ultra-high streptokinase (UHSK) infusion of 1.5 million IUSK/hour over a period of 6 hours (total SK dose: 9 million IU). A series of one to three UHSK infusions was given on one to three consecutive days. Forty patients were randomised to either systemic (Group S) or ipsipedal (Group IP) treatment. The distribution of important parameters determining a fibrinolytic response (e.g. the age, site and extent of DVT, and number of UHSK infusion series) was virtually identical in the two treatment groups. The rates for total and partial thrombolysis in the systemic infusion group were 50% and 10% respectively compared with 30% and 20% respectively in the ipsipedal group. The distribution of side-effects was approximately identical in the two groups. The results show that ipsipedal UHSK lysis via the dorsalis pedis vein confers no advantage over systemic infusion via the brachial vein.

Adult↗

[The effect of air within the infusion syringe on drug delivery of syringe pump infusion systems] .

Application of highly concentrated short-acting vasoactive drugs in the critically ill patient requires precisely working syringe pump systems for continuous intravenous drug delivery. We performed a bench study to investigate the consequences of small amounts of air entrapped within a 50-ml infusion syringe. In particular we studied the effect of entrapped air on drug delivery after moderate vertical displacement of the pump by 50 cm (e.g. in preparation for transport) and the effect on the time required to trigger the pressure alarm after occlusion of the infusion line. At a flow rate of 1 ml/h, lowering the syringe pump prolonged the zero-drug delivery time from (mean +/- SD) 4.1 +/- 0.8 min (without air) to 6.2 +/- 0.9 (with 1 ml air) and to 13.1 +/- 0.9 min (with 2 ml of air, p < 0.001 for all comparisons). Entrapping of 2 ml of air within the syringe resulted in a 2.6-fold prolongation of the occlusion alarm time after accidental occlusion of the infusion line and a 3-fold increase of the resulting infusion bolus after occlusion. Enclosed air within infusion syringes considerably affects the syringe compliance. It increases the susceptibility of constant drug delivery to vertical displacement of syringe pumps and impairs the occlusion alarm function. Therefore, any air in syringe of infusion pump systems should be carefully removed. To avoid infusion boluses of short-acting vasoactive drugs after accidental occlusions, the occluded infusion line should be released to ambient pressure first.

Air↗

Influence of infusion pump operation and flow rate on hemodynamic stability during epinephrine infusion.

OBJECTIVE: To determine whether variations in the flow rate of epinephrine solutions administered via commonly available infusion pumps lead to significant variations in blood pressure (BP) in vivo. DESIGN: Prospective, randomized, crossover study with factorial design, using infusion pumps with four different operating mechanisms (pulsatile diaphragm, linear piston/syringe, cyclic piston-valve, and linear peristaltic) and three drug delivery rates (1, 5, and 10 mL/hr). SUBJECTS: Two healthy, mixed-breed dogs (12 to 16 kg). INTERVENTIONS: Dogs were made hypotensive with methohexital bolus and continuous infusion. BP was restored to normal with constant-dose epinephrine infusion via two pumps at each rate. MEASUREMENTS: Femoral mean arterial pressure (MAP) was recorded every 10 secs. Pump-flow continuity was quantitated in vitro using a digital gravimetric technique. Variations in MAP and flow continuity were expressed by the coefficient of variation; analysis of variance was used for comparisons. RESULTS: The mean coefficients of variations for MAP varied from 3.8 +/- 3.1% (linear piston/syringe) to 6.1 +/- 6.6% (linear peristaltic), and from 3.4 +/- 2.2% (10 mL/hr) to 7.9 +/- 6.6% (1 mL/hr). The coefficients of variation for in vitro flow continuity ranged from 9 +/- 8% (linear piston-syringe) to 250 +/- 162% (pulsatile diaphragm), and from 35 +/- 44% (10 mL/hr) to 138 +/- 196% (1 mL/hr). Both the type of pump and infusion rate significantly (p < .001) influenced variation in drug delivery rate. The 1 mL/hr infusion rate significantly (p < .01) influenced MAP variation. Cyclic fluctuations in MAP of < or = 30 mm Hg were observed using the pulsatile diaphragm pump at 1 mL/hr. CONCLUSION: Factors inherent in the operating mechanisms of infusion pumps may result in clinically important hemodynamic fluctuations when administering a concentrated short-acting vasoactive medication at slow infusion rates.

Analysis of Variance↗

Subcutaneous infusion of cytosine arabinoside. A practical alternative to intravenous infusion.

The administration of cytosine arabinoside (araC) by continuous IV infusion requires the patient to be in hospital and have prolonged IV cannulation. In this study the pharmacokinetics of araC during continuous IV infusion were compared with those of continuous SC infusion in six patients with acute myelogenous leukaemia. Each patient acted as his own control. The mean plasma levels of araC reached a plateau within 2 h and the plasma concentrations and the area under the curve were similar for both methods of administration. The mean area under the curve (AUC) was 1147 +/- 230 ng/ml for the IV infusion and 1017 +/- 238 ng/ml for the SC infusion. The plasma araC concentrations showed wide interpatient variation, and there was also considerable variability in the plasma concentrations of araC within the individual patients after a plateau had apparently been reached. Subcutaneous infusion was well tolerated by the patients without any local discomfort or excoriation and SC infusion of araC is thus a feasible alternative to IV infusion. It allows the patients the benefits of being at home, while avoiding unnecessary thrombophlebitis.

Cytarabine↗

High-dose continuous venous infusion of interleukin-2: influence of dose and infusion rate on tumoricidal function and lymphocyte subsets.

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18 x 10(6) IU/m2 per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlated between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18 x 10(6) IU/m2 per day in a 5-day continuous infusion schedule.

Carcinoma, Renal Cell↗

The effects of intraoperative glucose infusion on portal blood insulin concentration and hepatic mitochondrial redox state during surgery: comparison of short-term and continuous infusions.

The relationships between the blood glucose level, portal blood immunoreactive insulin (IRI) concentration, ketogenesis, and hepatic mitochondrial redox state associated with intraoperative glucose administration were evaluated in patients undergoing total gastrectomy. A total of 26 patients were randomly allocated to two groups according to the type of infusion given; group 1 was given a short-term glucose infusion of 25 g in 30 min and group 2 was given a continuous glucose infusion of 10 g/h. The blood glucose concentration peaked 30 min after the glucose infusion was commenced, then decreased in group 1, despite a continuous rise in group 2. A temporary but significantly higher blood glucose level was observed in group 1 than in group 2, 30 and 60 min after the infusion was commenced. The portal blood IRI concentrations and arterial ketone body ratio (AKBR) continued to increase and the blood ketone body concentrations continued to decline after the start of the glucose infusion in both groups; however, after 60 and 120 min, the portal blood IRI and AKBR levels were significantly higher, and the blood ketone body levels significantly lower in group 1 than in group 2. These findings suggest that intraoperative glucose administration is beneficial for insulin secretion, ketogenesis, and the hepatic mitochondrial redox state, and that short-term infusion is superior to continuous infusion.

Aged↗

Prolonged gemcitabine infusion in advanced non-small-cell lung cancer with stable disease after gemcitabine 30-min infusion.

BACKGROUND: Although 30-min gemcitabine infusion has become the standard administration, pre-clinical and clinical studies have suggested the possibility that an infusion rate of 10 mg/m(2) per minute may be more effective. The main objective of this study was to investigate whether the pursuance of gemcitabine, administered at a prolonged infusion rate, was able to convert stable disease to objective response after two or three cycle of standard administration. The secondary end-point was the evaluation of the new schedule toxicity. PATIENTS AND METHODS: Thirty-eight patients, with stage IIIA-B and IV NSCLC already treated by two or three cycles of 30-min gemcitabine infusion, alone or in combination with cisplatin, were enrolled: 26 patients (aged <70 years) were treated with cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks and 12 patients (aged > or =70 years) were treated with gemcitabine alone 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks, for two courses. Simon's two stage minimax design was applied to calculate the sample size. Assuming p(0) (low conversion rate) 5%, p(1) (target conversion rate of interest) 20%, alpha error 0.05, beta error 0.10 a total of 29 evaluable patients had to be accrued during stage 1. In case at least one objective response was observed, a further nine evaluable patients had to be enrolled into the study during stage 2. The regimen was considered promising if > or =4 objective responses out of 38 evaluable patients were observed. RESULTS: Thirty-eight patients were evaluable for response and in five patients (with stable disease after two courses of gemcitabine 30' infusion) a partial response was observed (conversion rate 13.1%, 95% confidence interval 4.4-28%). Toxicities were more frequently observed with cisplatin plus 120-min gemcitabine infusion: grade 3-4 neutropenia, thrombocytopenia and anaemia in 28, 22 and 16% of the courses, respectively. CONCLUSIONS: The prolongation of gemcitabine infusion time is able to convert stable disease to partial response in 13% of the cases. The haematological toxicity seems enhanced with cisplatin plus gemcitabine prolonged infusion.

Aged↗

Continuous indomethacin infusion may be less effective than bolus infusions for ductal closure in very low birth weight infants.

The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates were determined in two groups: 16 preterm infants with PDA treated with continuous INDO infusion (CONTIN group) and 16 control patients, matched for gestational age, who received bolus INDO infusions (BOLUS group). The total dosage was the same for both groups. PDA closed in seven of 16 preterm infants in the CONTIN group and in 13 of 16 in the BOLUS group ( p = 0.033, Fisher's exact test). In infants < 1000 g it was two of eight in the CONTIN group and 10 of 10 in the BOLUS group ( p = 0.002). Continuous INDO infusion was more likely than bolus infusion to be associated with failure of ductal closure (odds ratio, 19; 95% CI, 1.5 to 247; p = 0.023). This indicates that continuous infusion of INDO may be less effective in closing PDA than bolus infusions, especially in extremely low birth weight infants.

Cardiovascular Agents↗

Development of individual insulin infusion profiles for open loop infusion systems.

A computer controlled syringe-type insulin infusion pump storing up to 254 different infusion rates, eight different meal programs and two different basal rates automatically changeable during 24 h in EPROM was used for insulin infusion applying a wavy step profile. This profile approaching the physiological postprandial insulin secretion of the B-cell was calculated by an algorithm following the biphasic insulin secretion model proposed by E. Cerasi . The computer program for the open loop infusion device simulated the feed-back structure of a closed loop insulin secretion control by an algorithm based upon a theoretical postprandial blood sugar profile. Fifteen unstable juvenile onset insulin requiring diabetics could be well controlled after two to three days of an intravenous open loop insulin infusion program. The programs consisted of two constant basal rates and superimposed wavy step profile programs activated at the beginning of each meal. The preabsorptive bolus or cephalic phase was an additional tool both for improved postprandial blood sugar control and further reduction of insulin consumption. The programmable insulin infusion device proved as a valuable tool for the study of a sophisticated insulin infusion profile suitable as well for open loop as for closed loop insulin infusion systems.

Adult↗

Cardiovascular effects of long-term endothelin infusion and responses to endothelin during ACTH infusion in conscious sheep.

Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg. This response was mediated by the vasoconstrictor effect of ET-1 and was accompanied by a fall in cardiac output. Plasma renin concentration fell throughout the infusion and atrial natriuretic peptide was increased on day 1 of ET-1 infusion. Hematocrit dramatically increased, probably mainly due to plasma loss resulting from the ET-1-induced increased capillary hydrostatic pressure. To determine whether increased pressor responsiveness to ET-1 played a role in the rise in MAP caused by corticotropin (ACTH), the responses to bolus doses of ET-1 were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5 micrograms/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. On the control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 +/- 1, 18 +/- 6 and 35 +/- 11 mm Hg, respectively. No initial vasodilation occurred. The responses to all doses of ET-1 were similar during ACTH infusion. Plasma levels of ET-1 did not increase during ACTH infusion. These results demonstrate that long-term infusion of ET-1 caused a sustained increase in blood pressure. There was no evidence that the sensitivity or responsiveness to ET-1 were altered during infusion of ACTH. In conclusion, ET-1 could play a role in the pathogenesis of hypertension but does not appear to be involved in the increase in blood pressure caused by ACTH.

Adrenocorticotropic Hormone↗

Proline is synthesized from glutamate during intragastric infusion but not during intravenous infusion in neonatal piglets.

Glutamate is considered the primary precursor amino acid for proline synthesis in mammals. Evidence exists, however, suggesting that proline may be a dietary indispensable amino acid for 2.5-kg piglets due to inadequate synthesis. This hypothesis was tested by intravenous and intragastric infusion of radiolabeled amino acids in vivo. Piglets (3 to 4 d old) were surgically implanted with catheters in the femoral (infusion) and jugular (sampling) veins and in the stomach (feeding and infusion). Piglets were fed hourly, via the stomach catheter, a semi-purified diet containing 10% dried skim milk, 15% corn oil, amino acids, vitamins and minerals. Experiment 1 was a 2 X 2 factorial design, with 24 piglets adapted to either low or supplemental proline diets (1.3 and 16.4 g proline x kg(-1) respectively) for 7 d, then intravenously infused with either [U-14C]glutamate or [U-14C]proline (185 k Bq x kg(-1) prime; 370 kBq x kg(-1) x h(-1) constant) for 4 h. Experiment 2 followed similar protocols, with eight piglets adapted to the low proline diet for 7 d and [U-14C]glutamate or [U-14C]proline infused into the stomach catheter. Piglets infused intravenously with [U-14C]glutamate did not convert glutamate to proline. Radioactive label was recovered in proline in all of the piglets receiving intragastric infusion of [U-14C]-glutamate. The fractional synthesis rate of proline from intragastric glutamate was 125 microgram ol kg(-1) x h(-1), accounting for approximately 40% of the proline accumulated. These data provide conclusive evidence that intravenously infused glutamate is not used as a precursor for proline synthesis and that, although conversion of glutamate to proline occurs in the gastrointestinal tract, the rate is not sufficient to provide the proline accumulated.

Animals↗

Simultaneous infusion of glutamine and branched-chain amino acids (BCAA) to septic rats does not have more favorable effect on protein synthesis in muscle, liver, and small intestine than separate infusions.

BACKGROUND: Glutamine and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are used as nutrition supplements in the treatment of proteocatabolic illness. We hypothesized that simultaneous administration of BCAA and glutamine affects protein metabolism more significantly than separate administration. In the present study, we evaluated their effect on protein synthesis in skeletal muscle, liver, and jejunum of septic rats. METHODS: Twenty-four hours after induction of sepsis by subcutaneous injection of turpentine, the rats were infused for 6 hours with 5 mL of 1.75% glutamine, 1.75% BCAA, 1.75% glutamine+BCAA, or saline solution. The control group consisted of intact rats infused with saline. Protein synthesis was measured at the end of infusion by a "flooding method" with [3,4,5-(3)H]phenylalanine. RESULTS: In turpentine-treated animals, we observed a decrease in glutamine concentration in blood plasma and skeletal muscle, a decrease in BCAA concentration in liver and jejunum, and a decrease in protein synthesis in all tissues. Glutamine or glutamine+BCAA infusion increased glutamine concentration in plasma and muscle and stimulated protein synthesis in the liver. The BCAA infusion enhanced concentrations of BCAA in plasma and tissues, but the effect of BCAA on protein synthesis was insignificant. Synergistic effect of simultaneous infusion of glutamine and BCAA on protein synthesis was not observed. CONCLUSIONS: We conclude that glutamine infusion to rats with septic injury may significantly improve impaired protein synthesis in the liver and that there is no synergistic effect of glutamine and BCAA infusion on protein synthesis in skeletal muscle, liver, and jejunum.

Amino Acids, Branched-Chain↗