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Modification of erythrocyte membrane lipid composition induced by a single intravenous infusion of phospholipid-triacylglycerol emulsions in man.

The study aimed to investigate whether, during short term infusion of lipid emulsions in man, red blood cell (RBC) membrane lipid composition was altered and RBC-free cholesterol (FC) could serve as a source of FC accumulated in the plasma. 3 normal subjects were infused intravenously with either 10% Intralipid [10% IL; PL:triglyceride (TG) weight ratio of 0.12] at the rates of 0.1, 0.2 and 0.3 g TG.kg(-1).h(-1) (providing PL intakes of 12, 24, 36 mg.kg(-1).h(-1), respectively) or with 30% Intralipid (30% IL; PL:TG ratio of 0.04) at the rate of 0.3 g TG.kg(-1).h(-1) (providing 12 mg PL.kg(-1).h(-1)). Infusion of 10% IL at a slow rate and 30% IL at a high rate caused no change in RBC and plasma FC content. However, 10% IL infusion at intermediate and high rates induced a significant decrease in RBC-FC: PL ratio. This change was still present at 18 h after the cessation of high rate infusion. RBC-FC: PL ratio and plasma PL measured during infusion were significantly correlated (r = -0.87, p < 0.001). FC efflux from RBC appears to contribute to the rise in plasma FC. This study indicates that the excessive amount of PL present as liposomes in some intravenous lipid emulsions can alter erythrocyte membrane lipid composition.

Journal Article↗

Some studies on the metabolism and the effects of 99Mo- and 35S-labelled thiomolybdates after intravenous infusion in sheep.

Sheep were infused intravenously with 99Mo- and 35S-labelled tri- and tetrathiomolybdates (1-2 mg Mo). Most of the plasma radioactivity was trichloroacetic acid (TCA)-insoluble after infusion, but the stability of this fraction was reduced by pre-infusion or subsequent infusion with unlabelled thiomolybdates. Most of the 99Mo and 35S was shown to be associated with albumin. It was concluded that compounds bound to albumin were relatively stable, but displaced or unbound thiomolybdates were rapidly hydrolysed to molybdate and sulphate. There was no evidence of an irreversible interaction of either 35S or 99Mo with copper in plasma, despite the appearance of a TCA-insoluble Cu fraction. Increased dietary Cu did not increase the retention of 35S in plasma or affect the exchangeability of 36S-labelled thiomolybdates bound to albumin.

Animals↗

Relation between lower esophageal sphincter (LES) pressure and the plasma concentration of neurotensin during intravenous infusion of neurotensin(1-13) and (Gln4)neurotensin(1-13) in man.

Ingestion of fat causes a pronounced decrease in lower esophageal sphincter (LES) pressure. This may be due in part to effects of neurotensin (NT), which is released postprandially after the ingestion of fat. The aim of the present investigation was to establish whether the LES pressure decreases at physiological plasma concentrations of NT(1-13). In addition, we have compared the effects and metabolism of NT(1-13) and (Gln4)NT(1-13). The experiments were performed in 3 healthy male volunteers who had fasted for at least 11 hours prior to the study. NT(1-13) or (Gln4)NT(1-13) were infused intravenously at a dose of 12 pmoles X kg-1 X min-1. LES pressure was monitored by a continuous pull-through method with a perfused catheter. The concentrations of chromatographically identified tridecapeptides were determined using NH2 and COOH-terminal directed antisera. Already one min after the start of the infusions the LES pressure had decreased by 43% of the control value. At that time the plasma concentration of the neurotensin tridecapeptide was about 15 pM. NT(1-13) and (Gln4)NT(1-13) had similar half-lives in plasma (2.5 min). NT(1-8) and (Gln4)NT(1-8) were found to be the main metabolites of NT(1-13) and (Gln4)NT(1-13) respectively. The results indicate that the increase in the plasma concentration of NT(1-13) seen after the ingestion of food is sufficient for neurotensin to function as a hormone of the endocrine type. NT(1-13) and (Gln4)NT(1-13) have the same effects on LES pressure in humans and show the same pharmacokinetic characteristics.

Adult↗

Effects of intravenous infusion of prostacyclin (PGI2) in man.

Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects. The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting. Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio.

Adult↗

Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers.

The effects of nitroglycerin, infused intravenously at 3.4 and 7.5 micrograms/min over 30 min, on haemodynamic parameters were determined in the morning and the afternoon in a randomized, placebo-controlled study in 5 healthy volunteers. The mean steady-state concentrations of nitroglycerin reached in the plasma during the infusions of 3.4 and 7.5 micrograms/min were 0.35 +/- 0.06 ng/ml and 0.64 +/- 0.22 ng/ml, respectively. Wide inter-individual variation was noted. The nitroglycerin-induced increase in the orthostatic rise in heart rate and the change in digital-pulse-wave morphology roughly paralleled the plasma concentration, whereas the reduction in systolic blood pressure in the upright position was still evident 15 mins after the infusion, i.e. when nitroglycerin was no longer measurable in plasma. No significant diurnal variation in vascular sensitivity to the vasodilative action of nitroglycerin was demonstrable. The change in pulse-wave morphology resulting from the reduction in peripheral resistance (shift of the dicrotic wave in the descending limb towards the base-line) proved to be the most sensitive haemodynamic parameter.

Adult↗

Factors affecting the voluntary intake of food by sheep. 3. The effect of intravenous infusions of gastrin, cholecystokinin and secretin on motility of the reticulo-rumen and intake.

1. Sheep given ground and pelleted lucerne hay (Medicago sativa) ad lib. were infused intravenously with pentagastrin, secretin, cholecystokinin (CCK) and its analogues to assess their effects on motility of the reticulo-rumen and on food intake. In the latter experiments the animals were deprived of their diet for periods of up to 6 h to induce hunger and the infusions were made before and during 3-10 min periods of feeding. 2. Pentagastrin, and analogue of gastrin, depressed intake by 35-50% (P less than 0.05) when it was infused at 9 microgram/kg per h during 30 min of feeding. The threshold may however be below 1 microgram/kg per h as this dose decreased intake of 12-17%. The frequency of reticular contractions decreased by 13, 35, 39 and 44% when 1, 3, 9, and 27 microgram pentagastrin/kg per h respectively was infused (P less than 0.025). 3. Secretin depressed food intake 38% after 30 min (P less than 0.025) when 8 Clinical Units (CU)/kg per h was infused but the threshold could be less than this dose since 0.5 CU/kg per h depressed intake by 12%. Contraction amplitude but not frequency decreased at 8 CU/kg per h. 4. CCK produced a 39% decrease in intake during the first 10 min of feeding (P less than 0.05) and the threshold was between 5 and 15 Ivy Dog Units (IDU) or 425 and 1276 pmol/kg per h. The frequency of reticular contractions was not affected by 1.7 IDU/kg per h but it was depressed 21 and 63% by 5 and 15 IDU/kg per h. Octapeptide at 1.5 and 3 microgram (1312 and 2624 pmol) kg per h depressed intake by 11 and 43% respectively after 10 min (not significant) and 1.5 microgram/kg per h depressed motility by 39% (P less than 0.01). Ceruletide at 810 ng (599 pmol)/kg per h depressed intake by 31% (not significant) after 10 min and decreased motility by 52% (P less than 0.05). The threshold dose for ceruletide on intake appeared to be about 90 ng or 66 pmol/kg per h which is considerably less than that for CCK or octapeptide. 5. The biological significance of gastrointestinal hormones as signals of satiety in normal sheep is not known since doses of pentagastrin and CCK that suppressed intake also interfered quite markedly with motility. However there is good reason to suspect that elevated concentrations of gastrin and CCK in blood of parasitized sheep may account at least in part for their symptoms of rumen atony and reduced food intakes.

Animals↗

Headache provocation by continuous intravenous infusion of histamine. Clinical results and receptor mechanisms.

Histamine, 0.16, 0.33 and 0.66 microgram/kg/min, was infused intravenously to 13 normal non-headache-prone volunteers, 10 patients with chronic muscle contraction headache and 25 patients with common migraine. In the normal group no patients developed pulsating headache. In the migraine group 13 patients developed severe, 9 patients moderate and 2 patients mild pulsating headache, and only 1 patient failed to develop headache at all. The muscle contraction headache patients responded intermediately. At each infusion rate the headache was of constant quality and severity as long as the infusion continued, but disappeared shortly after its termination. Injection of an H1 blocking agent, mepyramine, almost immediately abolished the headache. The H2 blocker cimetidine was much less effective, but still significantly better than placebo. The i.v. histamine infusion test is a useful model for the study of experimental vascular headache.

Aminopyridines↗

Effects of an intravenous infusion of noradrenaline on the plasma concentration of free and sulfoconjugated catecholamines in anesthetized dogs.

Exogenous noradrenaline (NA) was infused intravenously at increasing rate from zero (control) to 10, 25, 50, 100, 200 and 600 ng/kg/min during 20 min in anesthetized and ventilated dogs; the mean (+/- SEM) plasma concentration of free NA was increased from 130 +/- 23 pg/ml (basal) to 7,826 +/- 787 pg/ml. This had no measurable effect on the plasma concentration of dopamine and adrenaline in either free or sulfoconjugated form; a lack of change was also observed in dogs given a 600-ng/kg/min infusion during more than 2 h. The increase of free NA concentration was highly correlated both with the infusion rate, and with the blood pressure. Contrary to expectations, the plasma concentration of NA sulfate decreased in all 5 dogs when plasma NA concentration was progressively increased from basal to about 1,600 pg/ml; beyond this apparently crucial level (i.e. from about 1,600 to 7,826 pg/ml), the response of NA sulfate concentration was erratic, as it was in dogs given a 600-ng/kg/min infusion during more than 2 h. If the response of canine blood pressure is examined in the light of the level of free NA concentration, two mechanisms can be suspected: (1) when the NA level increased from basal to about 1,600 pg/ml, a direct action upon peripheral resistances was likely to be the predominant hypertensive mechanism; (2) beyond about 1,600 pg/ml, a combined effect of NA on both peripheral resistances and cardiac hemodynamics could have a role in the hypertensive process. Thus, a concentration of NA of about 1,600 pg/ml appears to be a landmark for both CA metabolism and circulatory homeostasis. Further studies will have to be carried out to investigate whether this represents the upper physiological concentration in the anesthetized dog.

Anesthesia↗

Pharmacokinetics of vinpocetine and its metabolite, apovincaminic acid, in plasma and cerebrospinal fluid after intravenous infusion.

The pharmacokinetics of vinpocetine (ethyl apovincaminate, Cavinton) and its metabolite, apovincaminic acid, was studied in patients with cerebrovascular disorders. Vinpocetine (1 mg/kg) was infused intravenously over 25 min. The elimination half-life of the parent drug in plasma was 4.7+/-2.13 h. Total clearance of vinpocetine was 0.79+/-0.1 1 h(-1) kg(-1). The presence of vinpocetine in cerebrospinal fluid shows that the drug is able to pass through the blood-brain barrier and reach the central nervous system which is a possible site of action. The maximum increase of cerebral blood flow (25%) was measured at 32 min after the start of the infusion.

Journal Article↗

Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition.

Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal inhibitory concentration for most bacterial strains. One very sick newborn infant died with overwhelming Klebsiella pneumoniae septicemia. No signs of renal toxicity or ototoxicity were found. The serum amino acids remained within the normal range, except in 1 child with cytomegalovirus infection and liver insufficiency.

Amino Acids↗

Pial arterial and venous reaction to intravenous infusion of nimodipine in cats.

The calcium-antagonist nimodipine was infused intravenously in ten cats using dosage rates of 0.5 to 3 micrograms kg-1 min-1. The reactions of pial arterial and venous vessels as well as mean arterial blood pressure (MAP) were studied. For analysis of pial vascular reactions, diameter variations were continuously monitored on 50 arterial and 22 venous portions using a multichannel videoangiometer. At 0.5 micrograms kg-1 min-1, pial arteries with a mean resting diameter of 81 microns dilated by 4% (p less than 0.0005); venous diameters decreased by 0.5% (n.s.); MAP declined by 2% (n.s.). At 1 microgram kg-1 min-1, arteries dilated by 25% (p less than 0.0005), venous diameters were diminished by 3.8% (n.s.), MAP decreased by 9% (n.s.). Further significant dilatation of pial arteries was observed at 2 and 3 micrograms kg-1 min-1, however, together with a significant fall of MAP. Arterial vessels smaller than 60 micrograms resting diameter dilated more than arteries above 60 micrograms. After the infusion was stopped, arterial dilatation by some 20% persisted for at least 20 minutes, even when MAP values returned to the resting level.

Animals↗

Pharmacokinetics of amitriptyline infused intravenously in man.

Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.

Adult↗

[Use of a 2-part model of i pharmacokinetics of gentaniycin for maintaining a constant blood concentration in infusion intravenous (an experimental study)].

Maintenance of constant antibiotic blood levels within the required ranges may be accomplished with mathematical modelling of the antibiotic pharmacokinetics. The problem solvation was illustrated on gentamicin. The kinetic analysis of the curves of the drug excretion from the blood after a one-moment intravenous administration of the antibiotic to cats provided estimation of the constants for a two-compartment model of its pharmacokinetics. The constant values were used for calculation of the intravenous infusion rate for gentamicin and the load dose value providing attainance and maintenance of the drug blood levels within the required ranges. The experimental testing of the regiments of gentamicin infusion showed satisfactory correlation of the theoretically supposed and practically found antibiotic blood levels.

Animals↗

[Absorption and metabolism of glycerin in the neonatal period. I. Speed of turnover of glycerin during continuous intravenous infusions in newborn infants of various gestational ages and in older infants].

Glycerol was infused intravenously over 2 hours in preterm and term appropriate-for-date and in term small-for-date infants at the age of 12 to 72 hours and 10 to 14 days and in infants at the age of 3 to 8 months. The dosage was 0.25.kg-1.h-1 and 0.5.kg-1.h-1, respectively. Less than 6 per cent of the glycerol injused were recovered in the urine irrespective of the dosage. The total clearance was 9.1 to 14.6 ml.kg-1. min-1 during the first weeks of life with 0.25 g.kg-1.h-1 glycerol irrespective of gestational age and intra-uterine growth retardation; and it rose to 31.8 ml.kg-1.min-1 in older infants. With 0.5.kg-1.h-1 glycerol the total clearance values were lower in all groups. The glucose blood level and the blood lactate concentration as well as the parameters of the acid-base-balance were not significantly influenced by glycerol.

Acid-Base Equilibrium↗

Modification of the blood-brain barrier permeability by vinorelbine: effect of intracarotid infusion compared with intravenous infusion.

Brain levels of the antineoplastic compound, vinorelbine, and its effects on the permeability of the blood-brain barrier (BBB) were studied. Preliminary experiments were carried out to define the dose of 10 mg/kg and the delay of 3 h after infusion required to induce BBB disruption. Vinorelbine was infused by i.c. or i.v. infusion to anesthetized male Sprague-Dawley rats. BBB disruption was evaluated qualitatively by the presence in the infused hemisphere of i.v. administered Evans blue dye (2%) and vinorelbine intratissular levels were measured by HPLC. After an i.c. infusion, there is an important variability in the degree of extravasation of Evans blue albumin complex, which is correlated with vinorelbine levels (p < 0.01). The percent of dose in brain tissue is less than 1%. After an i.v. infusion, the parenchyma is globally affected as shown by the uniform faint bluish staining of the two hemispheres. Vinorelbine levels are homogenous and similar to levels of brains graded + 1 after an i.c. infusion. These results seem to indicate that an i.c. infusion induces localized BBB disruptions while the effect of an i.v. infusion is global and that the gain in tissue level after an i.c. infusion is low compared with i.v. infusion.

Animals↗

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↗