scholarly journals Anesthetic Effects of Intramuscular Alfaxalone–Ketamine in Naked Mole Rats (Heterocephalus glaber)

Author(s):  
Neta Ambar ◽  
David Eshar ◽  
Trenton C Shrader ◽  
Hugues Beaufrère

In this study, adult intact male and female (n = 10) naked mole rats (Heterocephalus glaber) were anesthetized by using a combination of ketamine (20 mg/kg IM), and alfaxalone (4.0 mg/kg IM). Induction and recovery times were recorded. Vital parameters, including heart rate, respiratory rate, and reflexes, were monitored every 5 min during the anesthetic period. Anesthetic induction was smooth and rapid. Induction time was significantly longer in male rats (median, 325 s; range, 180 to 385 s) than in females (median, 145 s; range, 118 to 180 s). In addition, overall duration of loss of righting reflex was shorter in male mole rats (median, 50 min; range, 36 to 65 min) than females (median, 70 min; range, 60 to 85 min). Males largely had intact withdrawal reflexes, whereas females showed variable loss of both forelimb and hindlimb withdrawal reflexes. Neither recovery time (mean ± 1 SD, 16 ± 13 min) nor vital parameters differed between sexes. None of animals showed any anesthesia-related adverse responses. According to these findings, intramuscular AK is a safe and effective protocol that provides brief, light anesthesia in male naked mole rats and deeper anesthesia in females. We recommend adding analgesics when this AK protocol is used for pain-inducing or invasive procedures, and further studies evaluating higher doses and different combinations are indicated.

2007 ◽  
Vol 41 (3) ◽  
pp. 329-336 ◽  
Author(s):  
H C Alves ◽  
A M Valentim ◽  
I A S Olsson ◽  
L M Antunes

The combination of propofol and a rapid-acting opioid, such as fentanyl, sufentanil or remifentanil, is a relatively safe, total intravenous anaesthesia technique, commonly used in humans and which has been investigated in laboratory animals. The objective of this study was to evaluate these combinations for anaesthesia of mice by the intraperitoneal (i.p.) route. Sixty-seven mice, divided into groups of four, were used to test 28 combinations of propofol alone and propofol with fentanyl, sufentanil or remifentanil administered i.p. The dose ranges of drugs studied were propofol 50–200 mg/kg, fentanyl 0.2–0.4 mg/kg, sufentanil 0.05–0.1 mg/kg and remifentanil 0.2–1.0 mg/kg. The loss of righting reflex (RR) and the loss of pedal withdrawal reflex (PWR) were recorded along with the duration and quality of recovery. The results obtained in these studies were unpredictable. The same dose combinations of propofol and opioids were associated with different responses in different individuals. Higher doses did not induce loss of RR and PWR in all animals and were associated with high mortality rates. An adequate hypnotic level was only observed with higher doses of propofol. The synergistic effect of propofol and the opioids was not sufficient to allow surgical procedures. Animals that reached PWR loss showed tail rigidity, shaking limbs and scratched their heads with their forefeet. Higher opioid doses induced respiratory depression and higher death rates. The inconsistency between and within groups may be associated with the i.p. route. The results reported here show that the i.p. route is not appropriate for mouse anaesthesia using propofol alone or in combination with fentanyl, sufentanil or remifentanil.


2001 ◽  
Vol 35 (2) ◽  
pp. 172-179 ◽  
Author(s):  
P. Hedenqvist ◽  
J. V. Roughan ◽  
L. Antunes ◽  
H. Orr ◽  
P. A. Flecknell

The characteristics of two techniques of face-mask induction of desflurane anaesthesia (rapid or slow) were compared with the effects of slow isoflurane induction in five New Zealand White (NZW) rabbits. Slow induction used stepwise increments in vapour setting of 2% for desflurane and 0.5% for isoflurane at 30 s intervals. All animals were anaesthetized using each technique according to a randomized block design with one week between treatments. Observations were made of the quality of induction (any struggling or periods of apnoea) and the latency to, and the duration of loss of the righting and toe pinch reflexes recorded. Changes in respiratory rate, arterial blood gas and cardiovascular parameters were also recorded. Induction and recovery times were shorter with rapid desflurane induction in comparison to isoflurane (loss of righting reflex: 139 ± 27 s cf. 205 ± 48 s), but both techniques were associated with struggling and long periods of apnoea (> 1 min) during the first 4 min after administration. During this period a significant degree of bradycardia, hypercapnia and hypoxaemia occurred with both techniques, but these and the subsequent effects of rapid desflurane administration were less severe than with isoflurane. Slow induction with desflurane was tolerated best, with little or no deleterious behavioural or physiological effects, however excessively prolonged induction times (loss of righting reflex 337 ± 160 s) limits the application of this method. Desflurane, administered rapidly, appears to be a more suitable agent than isoflurane. However, as with isoflurane, anaesthesia should only be induced following oxygen supplementation.


2014 ◽  
Vol 121 (6) ◽  
pp. 1203-1216 ◽  
Author(s):  
Jason A. Campagna ◽  
Kevin Pojasek ◽  
David Grayzel ◽  
John Randle ◽  
Douglas E. Raines

Abstract Background: Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation “soft” (i.e., metabolically labile) etomidate analogue. The purpose of this study was to characterize CPMM’s pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. Methods: CPMM’s and etomidate’s hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs. Their pharmacokinetics were defined after single bolus administration and single bolus followed by 2-h infusion. Adrenocortical recovery times after single bolus followed by 2-h infusion of CPMM, propofol, etomidate, and vehicle were measured using an adrenocorticotropic hormone stimulation test. Results: Compared with etomidate, CPMM was half as potent as a hypnotic (ED50 approximately 0.8 mg/kg), was more rapidly metabolized, and had a shorter duration of sedative–hypnotic action. Recovery times after CPMM administration were also independent of infusion duration. After hypnotic infusion, adrenocorticotropic hormone–stimulated plasma cortisol concentrations were 4- to 27-fold higher in dogs that received CPMM versus etomidate. Adrenocortical recovery was faster in dogs after CPMM infusion versus etomidate infusion (half-time: 215 vs. 1,623 min, respectively). Adrenocortical responsiveness assessed 90 min after CPMM infusion was not significantly different from that after propofol infusion. Conclusion: The studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative–hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation.


2007 ◽  
Vol 107 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Michael T. Alkire ◽  
Jayme R. McReynolds ◽  
Emily L. Hahn ◽  
Akash N. Trivedi

Background Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors test this by separately attempting to block or enhance anesthetic-induced loss of righting in rats using intrathalamic microinjections of nicotine or its antagonist. Methods Rats were implanted with a cannula aimed at the thalamus or control locations. A week later, loss of righting was induced using sevoflurane (1.4 +/- 0.2%). A dose-parameter study (n = 35) first identified an optimal intrathalamic nicotine dose associated with arousal. Subsequently, this dose was used to pinpoint the thalamic site mediating the arousal response (n = 107). Finally, sevoflurane righting dose and response specificity were assessed after blocking nicotinic channels with intrathalamic mecamylamine pretreatment (n = 8) before nicotine challenge. Results Nicotine (150 microg/0.5 microl over 1 min) was the optimal arousal dose, because lower doses (75 microg) were ineffective and higher doses (300 microg) often caused seizures. Nicotine temporarily restored righting and mobility in animals when microinjections involved the central medial thalamus (P < 0.0001, chi-square). Righting occurred despite continued sevoflurane administration. Intrathalamic mecamylamine pretreatment did not lower the sevoflurane dose associated with loss of righting, but prevented the nicotine arousal response. Conclusions The reversal of unconsciousness found here with intrathalamic microinfusion of nicotine suggests that suppression of the midline thalamic cholinergic arousal system is part of the mechanism by which anesthetics produce unconsciousness.


2021 ◽  
Vol 73 (1) ◽  
pp. 108-114
Author(s):  
R.O. Kunz ◽  
C. Cardeal ◽  
L.E. Riekher Junior ◽  
L.G.E. Valle ◽  
S.T. Belettini ◽  
...  

ABSTRACT Ten free-living adult coatis (two males and eight females) were chemically restrained with "ZAD-50", a concentrated formulation prepared with the dehydrated content of a Zoletil/50® vial diluted with 0.25mL of 1% atropine, 0.265mL of Dormiun-V®, and 2.2mL of distilled water, being exactly 3.0mL. The formula was administered to each animal previously captured and physically contained with a net. The loss of righting reflex (RR) occurred at 2.3±0.8 minutes post-injection (MPI), with anesthesia beginning at 4.4±2.7 MPI. Myorelaxant and analgesia were considered excellent at all moments of the evaluation. Conscious reactions were observed at 78.7±22.2 MPI, the return of the RR occurred at 101 ± 18 MPI, and normal ambulation was acquired at 137.0±31.0 MPI. The mean values of physiological parameters measured every 10 minutes between 10 and 50 MPI were 152.2 heartbeats per minute for heart rate, 66.4 respiratory movements per minute for respiratory rate, 39.2oC for rectal temperature, 86.2% for SpO2 and 14.6 mmHg for systolic blood pressure. In the same times, the EEG registered sinus rhythm. No adverse reactions were observed, and the assessed vital parameters remained compatible with the state of chemical restraint.


1970 ◽  
Vol 64 (2) ◽  
pp. 265-272 ◽  
Author(s):  
A. A. van der Gugten ◽  
M. Sala ◽  
H. G. Kwa

ABSTRACT Eight female and eight male rats were castrated at the age of 8 to 10 weeks. Four spayed and four orchidectomized rats received one oestrone/cholesterol pellet (200 μg oestrone) on the day of operation (day 0), a second pellet on day 11 and a third on day 23. The remaining animals received four oestrone/cholesterol pellets at these times. The fluctuations in the prolactin levels in the circulation induced by the oestrogen challenges in these animals were followed during 31 days by radioimmunoassays performed on days 3, 7, 9, 14, 15, 17, 23, 24, 25, 28 and 31. The results suggested that the homoeostatic mechanism regulating plasma levels of prolactin was capable of withstanding the three time-spaced oestrogen challenges only in the spayed animals receiving the lower doses of oestrogen, since it allowed the mean values of the prolactin levels to remain fairly constant during the first 4 weeks. The levels in this group rose to much higher levels only on day 31. The higher doses of oestrone in the spayed rats and both dose levels of oestrone in the orchidectomized animals apparently resulted in a primary break-down of the homoeostatic mechanism, since the prolactin levels in the animals of these groups rose to much higher levels either on day 7 or on day 9. This was followed by a period during which the prolactin levels appeared to be more or less under control, until a second and probably definitive failure of the homoeostatic mechanism allowed the mean levels to rise sharply again.


1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.


1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


2016 ◽  
Vol 94 (6) ◽  
pp. 669-675 ◽  
Author(s):  
Mohsen Alipour ◽  
Fatemeh Adineh ◽  
Hossein Mosatafavi ◽  
Azam Aminabadi ◽  
Hananeh Monirinasab ◽  
...  

Long-term hyperglycemia associates with memory defects via hippocampal cells damaging. The aim of the present study was to examine the effect of 1 month of i.p. injections of AG on passive avoidance learning (PAL) and hippocampal apoptosis in rat. Eighty male rats were divided into 10 groups: control, nondiabetics and STZ-induced diabetics treated with AG (50, 100, 200, and 400 mg/kg, i.p.). PAL and the Bcl-2 family gene expressions were determined. Diabetes resulted in memory and Bcl-2 family gene expression deficits. AG (50 and 100 mg/kg) significantly improved the learning and Bcl-2, Bcl-xl, Bax, and Bak impairment in diabetic rats. However, negative effects were indicated by higher doses of the drug (200 and 400 mg/kg). Present study suggests that 1 month of i.p. injections of lower doses of AG, may improve the impaired cognitive tasks in STZ-induced diabetic rats possibly by modulating Bcl-2 family gene expressions.


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