scholarly journals Continuous Rate Infusion of Alfaxalone during Ketamine–Xylazine Anesthesia in Rats

2020 ◽  
Vol 59 (2) ◽  
pp. 170-175
Author(s):  
Kathleen Heng ◽  
James O Marx ◽  
Katechan Jampachairsi ◽  
Monika K Huss ◽  
Cholawat Pacharinsak
Keyword(s):  
Heart Rate ◽  
Body Temperature ◽  
Respiratory Rate ◽  
Female Rats ◽  
Sprague Dawley ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Surgical Stimulation ◽  
Rate Infusion

Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine–xylazine–alfaxalone (KXA) anesthesia with ketamine–xylazine (KX) anesthesia in Sprague–Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO2, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO2, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.

scholarly journals Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

2020 ◽  
Vol 59 (5) ◽  
pp. 531-538
Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker
Keyword(s):  
Rattus Norvegicus ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Laboratory Rodent ◽  
Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

scholarly journals A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats

2020 ◽  
Author(s):  
Arnold Gutierrez ◽  
Kevin M. Creehan ◽  
Michael A. Taffe
Keyword(s):  
Body Temperature ◽  
Spontaneous Activity ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Exposure System ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

AbstractBackgroundThe ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.ResultsInhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups.ConclusionsThis work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.

A STANDARDIZED METHOD FOR THE PRODUCTION OF HEMORRHAGIC SHOCK IN THE RAT

1955 ◽  
Vol 33 (3) ◽  
pp. 436-447 ◽  
Author(s):  
H. G. Downie ◽  
J. A. F. Stevenson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mortality Rate ◽  
Hemorrhagic Shock ◽  
Respiratory Rate ◽  
Rectal Temperature ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Standardized Method

Although the blood pressure is one of the important criteria in the standardization of hemorrhagic shock in the dog, it has rarely been used for this purpose in the rat. A method resembling the reservoir technique developed by Wiggers and Werle (1942) for the dog using blood pressure as the criterion has been modified for use with the rat. Male Sprague-Dawley rats weighing approximately 400 gm. were used. In the standardization of this technique the blood pressure was reduced to 30 mm. Hg in a 10-min. period of hemorrhage and then maintained at this level by subsequent small hemorrhages into the reservoir until reinfusion indicated the beginning of vascular collapse, at which time all the blood in the reservoir was returned. Considering that those animals which lived longer than 48 hr. were survivors, in a series of 27 animals, 21 died and 6 survived—a mortality rate of 78%.During the hypotensive period there was a consistent and steady drop in the respiratory rate and rectal temperature. The heart rate declined initially and tended to recover as the hypotensive period progressed. After reinfusion the blood pressure rose but. did not reach prehemorrhage levels. Hemorrhage into the bowel and convulsions were significant postreinfusion findings.

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

EFFECT OF NEONATAL ADMINISTRATION OF THYROXINE ON THE RATE OF SEBUM PRODUCTION IN RATS

1979 ◽  
Vol 83 (2) ◽  
pp. 199-203 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Normal Activity ◽  
Skin Surface ◽  
Postnatal Period ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sebum Production ◽  
Skin Surface Lipids ◽  
Neonatal Administration

Newborn Sprague–Dawley rats of both sexes were treated with 28 μg thyroxine (T4) daily for the first week of life. At the age of 80 days, the secretion rate of sebum was measured from the amount of skin-surface lipids extractable by acetone and which had been produced during 2 days. Treatment with such excess amounts of T4 during the early postnatal period significantly reduced the production of sebum in both male and female rats when compared with control rats and with rats deprived of food early in life. The thyroid, the pituitary gland, the testes and the seminal vesicles were significantly smaller but the weights of the ovaries and uteri remained relatively unaffected. There was a similar ratio of sex difference in the rate of sebum secretion irrespective of treatment. It is suggested that a reduction of sebaceous response in rats made thyrotoxic with large doses of T4 early in life was probably due to a decreased secretion of thyroid hormone which is required to maintain normal activity of the sebaceous glands.

ROLE OF THE GONADS IN THE REGULATION OF SEBACEOUS GLANDS IN RATS: COMPARISON OF THE EFFECTS OF CASTRATION AT AND AFTER BIRTH

1980 ◽  
Vol 85 (2) ◽  
pp. 261-265 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Skin Surface ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sebaceous Glands ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sequential Event ◽  
Sebum Production ◽  
Skin Surface Lipids

Sprague–Dawley rats were castrated either within 24 h of birth or at 4 weeks of age. Control animals were sham operated. Intact female rats were also included for comparison. Sebum production was assessed at 80 days of age by measuring the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days. The removal of the testes at birth reduced the activity of the sebaceous glands to a level more nearly approaching that seen in the female rats whereas castration at 4 weeks of age only partially decreased the rate of sebum secretion so that it was intermediate between the male and female rats. The weights of the pituitary gland, thyroid and adrenal glands increased after castration but there were no differences between rats castrated at birth and those castrated at 4 weeks of age except in the weight of the thyroid gland. It would appear that the role of the testes in the control of the activity of the sebaceous glands is a sequential event which has already started at birth.

Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Robert M Carey
Keyword(s):  
Receptor Activation ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Angiotensin Iii ◽  
Compound 21 ◽  
Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

Maximum oxygen consumption of rats and its changes with various experimental procedures

1979 ◽  
Vol 47 (6) ◽  
pp. 1278-1283 ◽  
Author(s):  
T. G. Bedford ◽  
C. M. Tipton ◽  
N. C. Wilson ◽  
R. A. Oppliger ◽  
C. V. Gisolfi
Keyword(s):  
Test Procedure ◽  
Repeated Measurements ◽  
Female Rats ◽  
Shr Rats ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto ◽  
Different Strains

A ten-stage treadmill test was developed and standardized to secure the VO2max of male and female rats assigned to various cross-sectional and longitudinal experimental groups. Repeated measurements indicated that the test procedure was reliable and could be used for research purposes. When the test was used with different strains, the untrained Sprague-Dawley rats had significantly higher VO2max values than animals of the Wistar-Kyoto (WKY) or the Okamoto-Aoki (SHR) strains. Exercise schedules were evaluated that were similar to those previously used by various investigators and it was found that most were exercising their rats at levels exceeding 75% VO2max. After 6--10 wk of chronic exercise, significant increases in VO2max occurred that ranged between 12 and 26%. Longitudinal studies (1 yr) with hypertensive (SHR) rats revealed that it was more desirable to logarithmically evaluate the relationship between VO2max and body mass than by the conventional method of ml . kg-1 . min-1. When this approach was used with SHR animals, the VO2max differences between the sexes were not apparent until the animals were 1 yr of age. On the other hand, training by male SHR rats caused significant increases in VO2max regardless of the method used to express the results. It is recommended that future studies designed to elucidate exercise mechanisms in rats should include a standardized VO2max test.

Role of prostaglandins in exercise-induced core temperature elevation in female Sprague-Dawley rats

1993 ◽  
Vol 265 (5) ◽  
pp. R1121-R1125
Author(s):  
P. J. Rowsey ◽  
K. T. Borer ◽  
M. J. Kluger
Keyword(s):  
Body Temperature ◽  
Sodium Salicylate ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Temperature Elevation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Exercise Induced ◽  
Running Wheels

Female Sprague-Dawley rats (12:12-h photoperiod; body temperature, BT, measured with biotelemetry) with access to running wheels for 6 wk have an elevated BT (compared with rats with no access to exercise wheels, i.e, sedentary) both during the period of voluntary exercise (nighttime) (0.5 degree C, P = 0.0001) and the nonexercise period (daytime) (0.3 degree C, P = 0.002). To determine whether prostaglandin (PG) E was responsible for any portion of this daytime rise in BT, we injected a dose of sodium salicylate (300 mg/kg), which was shown to produce complete antipyresis in rats injected with lipopolysaccharide (LPS), into exercised and sedentary rats 4 h after the onset of the lights-on period. The injections of sodium salicylate led to a fall in body temperature in both the exercised and sedentary rats of similar amounts (-0.88 degree C vs. -0.61 degree C at 2 h postinjection, P = 0.59). We conclude that the increase in daytime BT of exercised female rats is not mediated by prostaglandins.

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