Continuous intravenous infusion in the unrestrained rat — procedures and results

1995 ◽  
Vol 14 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Desmond A. Cave ◽  
Ankie C.M. Schoenmakers ◽  
Hans J. van Wijk ◽  
Ilona C. Enninga ◽  
Jan C.M. van der Hoeven

1 A method of continuous infusion in the unrestrained rat is described, which provides a scientifically accept able and easily maintained rodent model for use in toxicological investigations. 2 Sprague Dawley SPF rats had cannulas implanted into the vena cava via the femoral vein, and were continu ously infused with physiological saline for a total of 28 or 90 days. 3 The results indicate that there was no change in body weight, food consumption, clinical observations or clinical biochemistry of infused rats when compared to non-infused rats. There were small changes in haema tological parameters, however none were toxicological ly significant. Urinary volume was increased and uri nary specific gravity and osmolality were decreased. At macroscopic and microscopic examination there were findings of scar formation associated with the area of surgery and minimal irritation in the area of the vena cava which accommodated the cannula. 4 These results indicate that implantation of a cannula into the vena cava of a rat and subsequent continuous intravenous infusion of physiological saline produces no toxicological adverse effects over a period of 90 days. Consequently, this model can be recommended for the continuous intravenous administration of test substances to rats.

1994 ◽  
Vol 13 (1) ◽  
pp. 40-47 ◽  
Author(s):  
C.J. Perkin ◽  
R. Stejskal

Continuous intravenous infusion allows the intended clinical dosing regime to be better evaluated during preclinical studies. Depending on the test material and vehicle, infusion for up to 6 months in primates and 12 months in beagle dogs is possible, but 28 days is the most frequent duration. Under general anesthesia, medical grade catheters are placed in the vena cava via the femoral vein, passed subcutaneously, and exteriorized between the scapulae. A jacket and tether system are used to connect the catheter to an external pump for dosing and the animals are allowed to move freely within the cages. Dosing usually commences after a 1-week recovery period. Body weight gain, food intake, and general observations indicate that the procedure does not adversely affect the normal laboratory behavior of the animals. Test article infusion periods from a few minutes up to 24 h a day, 7 days a week are used; a low infusion rate ofsaline is used for the balance of the 24-h period. Dosage volumes up to 120 ml/kg/day can be infused for 28 days and larger volumes for shorter periods. Up to three separate catheters can be inserted to allow coadministration of compounds for assessment of potential interactions. Body weight, ophthalmoscopy, blood sampling, electrocardiography, and indirect blood pressure measurement can be performed during infusion. Histopathologic common changes in all species include thrombosis, proliferation of vascular intima, and various local inflammatory changes at the infusion site in the vicinity of the catheter tip. These generally are considered to be due to physical irritation by the catheter. Secondary changes include pulmonary microemboli or thrombosis and histiocytosis in hepatic sinusoids often with erythrophago-cytosis. The main findings associated with infusion of very large volumes are reticulocytosis and increased hematopoiesis. These spontaneous findings must be distinguished from those possibly related to administration of the test material and/or vehicle.


2015 ◽  
Vol 70 (5-6) ◽  
pp. 151-157 ◽  
Author(s):  
Ye Pan ◽  
Peng Lü ◽  
Lijing Yin ◽  
Keping Chen ◽  
Yuanqing He

Abstract Two-dimensional gel electrophoresis (2-DE) was used to detect fluoride-induced alterations in the proteome of the rat hippocampus. Male Sprague-Dawley rats (n=30) were subjected to treatments three weeks after weaning. Animals of the first group were injected intraperitoneally (i.p.) with aqueous NaF (20 mg/kg/body weight/day), the second group, injected with physiological saline, served as the control. After 30 days, the body weight of the fluoride-treated rats was lower than that of the control, and F– levels in serum were higher than in the control. The hippocampus was subjected to proteomic analysis, and the fluoride-treated group was found to contain 19 up-regulated and eight down-regulated proteins. The proteins, identified by mass-spectroscopic analysis of their fragments obtained after digestion, were found to be involved in amino acid biosynthesis, the insulin signaling pathway and various other crucial functions. Our results also provide useful information on the mechanism of the reduction of the learning ability and memory induced by F.


1954 ◽  
Vol 32 (4) ◽  
pp. 428-433 ◽  
Author(s):  
B. Kinash ◽  
R. E. Haist

A method is described for the continuous intravenous infusion of fluids in the unanesthetized rat. When rats were infused continuously with glucose solutions for 6–14 days the total amount of islet tissue was greatly increased, as compared to that of saline-infused controls. This increase was evident also when considered in relation to pancreas weight or body weight.


2006 ◽  
Vol 31 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Kentaro ASANUMA ◽  
Shun-ichiro KOMATSU ◽  
Takayuki SAKURAI ◽  
Ryo TAKAI ◽  
Shuichi CHIBA

1996 ◽  
Vol 15 (3) ◽  
pp. 214-218 ◽  
Author(s):  
Paul C Barrow ◽  
Jean-Yves Guyot

1 This investigation was undertaken to evaluate the suitability of an intravenous infusion technique in the pregnant rabbit. 2 18 New Zealand White rabbits were anaesthetised on day 1 of gestation and an indwelling catheter was implanted into the superior vena cava by introduction into the jugular vein. The catheter was attached by a tether system to a remote infusion pump. 3 The pregnant rabbits were infused with physiological saline at a rate of 4 ml kg-1 day-1 until day 19 of gestation. A caesarean examination was performed on day 29 of gestation. The results obtained were compared with historical control data from 150 mated rabbits. 4 Anaesthesia and catheter implantation caused a slight transient reduction in maternal food consumption and weight gain. Pregnancy rate, pre-implantation loss and early resorption incidence were not affected. 5 Late resorption incidence and post-implantation loss were higher in the infused group by comparison with the historical controls but the individual data did not suggest an effect of treatment. Foetal weight was not adversely influenced. Three of the infused dams each contained one malformed foetus: a possible influence of infusion in the aetiology of these abnormalities cannot be excluded nor confirmed within the limitations of this experiment.


1998 ◽  
Vol 275 (4) ◽  
pp. E709-E716 ◽  
Author(s):  
G. Livesey ◽  
P. D. G. Wilson ◽  
M. A. Roe ◽  
R. M. Faulks ◽  
L. M. Oram ◽  
...  

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 ( Endocrinol. Metab. 38): E717–E728, 1998]. We questioned whether, in healthy humans,d-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 gd-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating ∼15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion ofd-[6,6-2H2]glucose. Whereas 98 ± 2% ( n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 ± 9% ( n = 7) of midjejunally infused glucose did so, implying that 65 ± 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.


1954 ◽  
Vol 32 (1) ◽  
pp. 428-433 ◽  
Author(s):  
B. Kinash ◽  
R. E. Haist

A method is described for the continuous intravenous infusion of fluids in the unanesthetized rat. When rats were infused continuously with glucose solutions for 6–14 days the total amount of islet tissue was greatly increased, as compared to that of saline-infused controls. This increase was evident also when considered in relation to pancreas weight or body weight.


2020 ◽  
Vol 1 (30) ◽  
pp. 30-36
Author(s):  
E. A. Krylova ◽  
D. V. Aleinik

The article presents the results of a study of the effectiveness of the use of an inhibitor of pancreatic enzyme secretion of octreotide (Octrade) for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). It was shown that the administration of Octrade at a dose of 0.3 mg in 500 ml of 0.9 % NaCl by continuous intravenous infusion for 7 hours and then 0.1 mg of Octrade subcutaneously at 6 and 12 hours after the end of intravenous infusion significantly reduced the frequency of pancreatitis (4.0 % and 22.2 %; p < 0.05) and hyperamylasemia (8.0 % and 25.9 %; p < 0.05) after ERCP. It is concluded that Octrade is effective in preventing the development of pancreatitis and hyperamilasemia after ERCP.


2021 ◽  
Vol 9 (4) ◽  
pp. e002193
Author(s):  
Sigrid P Dubois ◽  
Milos D Miljkovic ◽  
Thomas A Fleisher ◽  
Stefania Pittaluga ◽  
Jennifer Hsu-Albert ◽  
...  

BackgroundFull application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8+ lymphocytes and natural killer (NK) cells. To ease rhIL-15 administration, we shortened time of infusion. Treatment with rhIL-15 at a dose of 3–5 µg/kg as a 5-day continuous intravenous infusion (CIV-5) had no dose-limiting toxicities while effector cell stimulation was comparable to the CIV-10 regimen.MethodsEleven patients with metastatic cancers were treated with rhIL-15 CIV-5, 3 µg (n=4), 4 µg (n=3), and 5 µg/kg/day (n=4) in a phase I dose-escalation study (April 6, 2012).ResultsImpressive expansions of NK cells were seen at all dose levels (mean 34-fold), including CD56bright NK cells (mean 144-fold for 4 µg/kg), as well as an increase in CD8+ T cells (mean 3.38-fold). At 5 µg/kg/day, there were no dose-limiting toxicities but pulmonary capillary leak and slower patient recovery. This led to our choice of the 4 µg/kg as CIV-5 dose for further testing. Cytolytic capacity of CD56bright and CD56dim NK cells was increased by interleukin-15 assayed by antibody-dependent cellular cytotoxicity (ADCC), natural cytotoxicity and natural killer group 2D-mediated cytotoxicity. The best response was stable disease.ConclusionsIL-15 administered as CIV-5 substantially expanded NK cells with increased cytotoxic functions. Tumor-targeting monoclonal antibodies dependent on ADCC as their mechanism of action including alemtuzumab, obinutuzumab, avelumab, and mogamulizumab could benefit from those NK cell expansions and provide a promising therapeutic strategy.Trial registration numbersNCT01572493, NCT03759184, NCT03905135, NCT04185220 and NCT02689453.


1984 ◽  
Vol 247 (5) ◽  
pp. R792-R799 ◽  
Author(s):  
P. J. Kahrilas ◽  
R. C. Rogers

Studies were performed to identify the response characteristics of nucleus of the solitary tract neurons receiving afferent projections from the hepatic branch of the vagus nerve. Thirty Sprague-Dawley rats under pentobarbital anesthesia had catheters placed in the ileocolic vein and the inferior vena cava. Neuronal recordings were made in the left medial nucleus of the solitary tract (NST), in the area where hepatic vagal fibers terminate. Sixteen NST cells were identified that responded selectively to the portal infusion of water or hypertonic saline. Two patterns of response were seen: 1) 12 neurons were persistently stimulated by portal hypertonic saline and persistently inhibited by portal water, and 2) four neurons were either transiently excited (n = 3) or transiently inhibited (n = 1) by portal hypertonic saline with no water effect. All units recorded responded to changes of 1% or less in portal blood sodium concentration. Hypertonic mannitol was an ineffective stimulus but choline chloride was as effective as sodium chloride. This suggests that the hepatic receptors utilize an Na+-K+-ATPase electrogenic pump in the transduction process.


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