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,1

IMMOBILIZATION OF CAPTIVE PINE MARTENS

(MA RTE S MART E S) WITH MEDETOMIDINE_KETAMINE AND
REVERSAL WITH ATIPAMF,ZOLE
Jon M. Arnemo, D.V.M., Randi O. Moe, D.V.M., and Nils E. Sli, D.V.M., Dr.Med.Vet.

Abstracl: Six captive pine martens (Martes martes) were immobilized with a combination of
medetomidine hydrochloride (MED) and ketamine (KET) in three experiments (Experiment l, July
199 l;Experiment 2, November l99l; Experiment 3, January 1992)to establish a dose range for
field use and to assess potential seasonal influence on drug effects. The mean + SD i.m. doses (range)
used in these three experiments were 0.19 + 0.03 (0)44j4) melkg MED + 9.3 + 1.5 (7.1-l1.8)
mg/kg KET,0.l7 + 0.04 (0.14-0.24)mg/kg MED + 8.6 + 1.8 (7.1-11.8) mg/kg KET, and 0.15
+b.01 (0.13-O.17)mg/kgMED + 7.6 + 0.8 (6.5-8.9) mg/kg KET, respectively. These doses induced
complete immobilization with good muscle relaxation and loss of both the corneal and pedal
withdrawal reflexes in all animals. The induction times were 4.3 + 1.6 (2.0-6.0) min, 3.8 + 0.8
(3.0-5.0) min, and 4.5 + 1.9 (3.0-8.0) min, respectively. Side effects included hypothermia, bradycar-
dia, and bradypnea, but all animals recovered completely without clinical complications. Blood
samples were drawn from immobilized animals and sera were analyzed for 24 different measures
(enzymes, metabolites, minerals, and electrolytes). Hyperglycemia occurred in all animals, but there
were no clinically important differences in serum chemistry values among the experiments. Forty
minutes after administration of MEDKET, the animals in Experiments I and 2 were given ati-
pamezole hydrochloride (ATI) i.m. at five times the MED dose. In Experiment 3, the animals
received saline i.m. for comparison. Immobilization was rapidly reversed by ATI, and side effects
such as muscle rigidity and incoordination were of short duration. The mean time from ATI injection
to mobility in Experiments I and 2 was7.7 + 2.3 (4.8-10.0) min and 3.8 + 1.6 (2.0-5.8) min,
respectively. The mean mobility time was 31.7 + 21.8 (1 1.0-59.0) min in the saline-treated animals,
and recovery was accompanied by prolonged sedation, incoordination, and motor impairment.
MED in combination with KET and reversed with ATI at a dose ratio of 5: I relative to MED was
a safe and effective immobilization protocol for captive pine martens.
Key words: Pine marten, Martes martes, immobilization, medetomidine, ketamine, atipamezole.

INTRODUCTION how this seasonal variation in the energy

Pine martens (Martes martes) are difficult
to handle, and most clinical procedures re-
quire chemical restraint of the animals.
Halothane, ketamine, and ketamine in
combination with promazine, diazepam,
xylazine, or medetomidine have been used
in pine martens and other Martes spe-
In Captive pine martenS,
CieS.3.6-8.r0.r1.rs,r8,20,23
both feed intake and locomotor activity var-
ies significantly with the ambient temper-
ature,r6 but no studies have been done on
From the Center ol Veterinary Medicine, N-9005
Troms, Norway (Amemo); the Dal Research Farm,
Norwegian College of Veterinary Medicine, Rustad-
veien l3l, N-1380 Heggedal, Norway (Moe); and the
Department of Pharmacology, Microbiology, and Food
Hygiene, Norwegian College of Vetcrinary Mcdicinc,
P.O. Box 8146 Dep., N-0033 Oslo, Norway (Sli).
548
economy may influence drug effects and dose
requirements.
Medetomidine-ketamine combinations
have been used successfully to immobilize
other mustelids2'14,r7'2r and furbearers.r,r2'r4
Medetomidine is a highly potent and selec-
tive alphar-adrenoceptor agonist that po-
tentiates ketamine to a greater extent than
does xylazine, reducing the effective ketam-
ine dose by as much as J So/o.tt This is of
great importance when reversal agents are
used in animals immobilizedwith ketamine
combinations, because a specific antagonist
to dissociative anesthetics has not been
found.5,re
The use of reversal agents has not been
reported in Martes species, although such
drugs would be very useful in field capture
and release studies,rs in clinical practice to
 ARNEMO ET AL._IMMOBILIZATION OF PINE MARTENS
avoid prolonged recovery, and for treat-
ment of relative overdosing. Atipamezole,
the most potent and selective alphar-adre-
noceptor antagonist currently known,22 has
been used for rapid reversal of immobili-
zationand anesthesia induced by medetom-
idine-ketamine in a wide range of zoo and
wild animal species. t'z'+'tn'tz'zt
The purpose of this study was to evaluate
medetomidine-ketamine and atipamezole
for reversible immobilizarion in pine mar-
tens under field conditions and to assess po-
tential seasonal influence on drug effects.
MATERIALS AND METHODS
Six 1-5-yr-old clinically healthy pine
martens (five males, one female) were im-
mobilized with medetomidine-ketamine on
three occasions (July 1991, November 1991,
and January 1992) at the Dal Research
Farm, Norwegian College of Veterinary
Medicine, Heggedal, Norway. The animals
were wildborn and had been captured as
pups from four different litters. They were
individually housed in tin-roofed wire cages
(1 mt) with a wooden nest box and were
kept on a standard feed regime for mink
(Dal Research Farm).
In Experiment I (July l99l) all animals
were given 0.2 mg/kg of medetomidine hy-
drochloride (Domitoro, I mglml, Orion
Corp. Animal Health Division, Turku, Fin-
land) and l0 mg/kg of ketamine (Ketalaro,
50 mglml, Parke-Davis, Barcelona, Spain)
from separate syringes, with doses based on
their estimated body weights. Each animal
was restrained with a net, and the drugs were
injected in the right gluteal muscle. The an-
imals were then released in their cages, and
the time to complete immobilization and
tolerance of dorsal recumbency (induction
time) was recorded. All animals were then
weighed and the actual doses ofdrugs per
kilogram of body weight were calculated.
The following measures were recorded ap-
proximately 15,25, and 35 min after injec-
tion of medetomidine-ketamine: rectal
temperature (using a digital thermometer),
heart rate (using a stethoscope), respiratory
549
rate (observing flank movements), pedal
withdrawal reflex-absent or present
(pinching of a toe with an artery forceps),
and corneal reflex-absent or present (light
touching of the cornea with a cotton-tipped
applicator). Reactions to handling (moving
ofthe head, curling up, or resistance to dor-
sal recumbency) were used as signs of spon-
taneous recovery. Twenty to 30 min after
administration of medetomidine-ketam-
ine, blood samples were drawn from the
jugular vein using the Venoject@ system with
5-ml tubes and 0.8- x 40-mm needles (Ter-
umo Europe N.V., 3001 Leuven, Belgium).
Blood samples were centrifuged within 2 hr
after collection, and the serum was sepa-
rated, stored in a refrigerator, and brought
to the laboratory for analyses the next day.
Serum measurements of aspartate amino-
transferase (AST), alanine aminotransferase
(ALT), creatine kinase (CK), lactate dehy-
drogenase (LDH), alkaline phosphatase
(ALP), gamma glutamyl transferase (GGT),
amylase, lipase, total protein, albumin,
globulin, glucose, cholesterol, triglycerides,
free fatty acids (FFA), urea, creatinine, total
bilirubin, phosphorus (P), calcium (Ca),
magnesium (Mg), sodium (Na), potassium
(K), and chloride (Cl) were perlormed by
standard procedures at the Central Labo-
ratory for Clinical Chemistry at the Nor-
wegian College of Veterinary Medicine.
Forty minutes after administration of med-
etomidine-ketamine, atipamezole hydro-
chloride (Antisedan@, 5 mg,/ml, Orion Corp.
Animal Health Division) was injected in the
left gluteal muscle at five times the dose of
medetomidine hydrochloride. The time un-
til the animal lifted its head from the floor
(head by time) and the time until it was able
to move either by crawling or walking (mo-
bility time) were recorded. All animals were
observed for at least 2 hr after administra-
tion of the antagonist to evaluate the quality
of recovery and to detect drug-related side
effects of abnormal behavior. The ambient
temperature was recorded during the ex-
periment.
In Experiments 2 (November 1991) and
550 JOURNAL OF ZOO AND WILDLIFE MEDICINE

Table 1. Data from six captive pine martens (Marles martes) immobilized with medetomidine-ketamine
on three different occasions."

Experiment I Experiment 2 Experiment 3

(Jul l99l) (Nov l99l) (Jan 1992)

Ambient temperature 14 to 19 -2to0 -5 to -3

("c)
Body weight 1.8 + 0.3 2.0 + 0.6 2.2 + 0.5
(ke) (t.4-2.2) ( 1 .3-2.8) (t.3-2.9)
Medetomidine HCI 0.19 + 0.03 0.17 + 0.04 0.15 + 0.01
(mglkg i.m.) (0.14-o.24) (0.t44.24) (0. l3--0.1 7)

Ketamine 9.3 + 1.5 8.6 + 1.8 7.6 + 0.8

(mglkg i.m.) (7. 1-l 1.8) (7. r-r 1.8) (6.5-8.e)
Induction time 4.3 + 1.6 3.8 + 0.8 4.5 + t.9
(min) (2.0-6.0) (3.0-5.0) (3.0-8.0)
Atipamezole HCI 0.93 + 0.15 0.86 t 0.18 saline
(mglkg i.m.) (0.7 r-r.18) (0.7 r-1.18)
Head up lime 6.5 + l.7b 3.1 + 1.3 not recorded
(min) (4.0-8.3) (2.0-4.8)
Mobility time 7.7 -r 2.3n 3.8 + 1.6. 31.7 + 21.8
(min) (4.8-10-0) (2.0-5.8) (l 1.0-59.0)

'Values are expressed as means + SD (range).

b. Superscripts denote a significant difference (P < 0.05) between means in Experiments I and 2 and between means in
Experiments 2 and 3, respectively.

3 (January 1992), each animal receiyed the
same total dose of medetomidine-ketamine
as in Experiment I irrespective of any gain
or loss of body weight, and all the proce-
dures from Experiment I were repeated ex-
cept that in Experiment 3 the animals were
given saline (the same volume as the an-
tagonist) instead of atipamezole.
Analyses of data were performed using
NCSS@ (Number Cruncher Statistical Sys-
tem, Kaysville, Utah 84037, USA). Statis-
tical comparisons were made between Ex-
periments I and 2, and Experiments 2 and
3, respectively. Within each experiment, a
comparison between the first and last re-
cording of the physiological measures was
made. A paired l-test was used to compare
body weights, drug doses, induction times,
head up times, mobility times, rectal tem-
peratures, heart rates, and respiratory rates,
and the Wilcoxon matched pairs test was
used to compare serum chemistry values.
RESULTS
Most animals gained weight in both pe-
riods between the experiments, but the dif-
ferences in mean body weight, mean doses
of medetomidine and ketamine, and mean
induction time were not significant (Table
l). Induction was very smooth with no ex-
citatory phase or abnormal behavior. All
animals were completely immobilized
within 8 min of medetomidine-ketamine
administration, and they remained immo-
bilized for at least 30 min. Muscle relaxa-
tion was good, and blood sampling was eas-
ily performed. Immobilized animals had
open eyes, and most had frequent, rhyth-
mical contractions of the upper lip and eye-
lids.
In all animals, both the corneal and pedal
withdrawal reflexes were absent 15 and 25
min after administration of medetomidine-
ketamine. In Experiment l, there were no
signs ofspontaneous recovery before the an-
tagonist was given, but in two individuals
the corneal reflex was present 35 min after
medetomidine-ketamine injection. In four
animals in Experiment 2, the corneal and
pedal withdrawal reflexes were present 35
min after administration of medetomidine-
ketamine, and two ofthem also showed signs
 ARNEMO ET AL.-IMMOBILIZATION OF PINE MARTENS 551

Table 2. Means (SD) of serial recordings of rectal than during Experiment 3 at the first re-
temperature, heart rate, and respiratory rate in six cap- cording.
tive pine martens (Martes marles) immobilized with
medtomidine-ketamine on three different occasions- The results of the serum chemistry anal-
yses are summarized in Table 3. Significant
Experiment I ExPeriment 2 Experiment 3 differences in mean values were seen for am-
Measure (Jul l99l) (Nov l99l) (Jan 1992)
ylase, total bilirubin, and sodium between
Rectal temperature ("C) Experiments 2 and 3.
15 min" 40.1 (0.6)b 37.9 (1.8) 38.8 (1.4) The mean head up and mobilitY times
25 min 39.2 (l.l)"
36.1 (2.0I 37.4 (r.5) were significantly lower during Experiment
35 min 38.4 (1.2)b 35' I (2.0)' 36.3 (1.5)
2 than during Experiment I (Table l). All
Heart rate (beats/min) animals in Experiments 1 and 2 appeared
I 5 min' I 16 (24) l2l (24) l 29 (35) alert and were able to walk 15 min after
25 min I l0 (17) 94 (18) 108 (33)
administration of atipamezole, but most of
35 min 95 (16) 90 (l2F 92 (27)
them showed various degrees of muscle ri-
Respiratory rate (breaths/min) gidity and incoordination. No other side ef-
15 min' 66 (6) 57 (18)' 7l (14)
fects were noted, and all individuals were
25 min 67 (10) 49 (16) 60 (17)
considered normal within I hr after injec-
35 min 64 (6) 47 (18)d 52 (16)
tion of the antagonist. In Experiment 3, all
' Time after medetomidine-ketamine injection. animals showed signs of sedation and in-
b'Superscripts denote a significant difference (P < 0.05) be-
tween means in Experiments I and 2 and between means in
coordination for at least 25 min after mo-
Experiments 2 and 3, resPectivelY. bility was regained. Two individuals with
extended mobility times (53 and 59 min)
were sedated and incoordinated 2 hr after
saline administration, and another hour
of spontaneous recovery (no recording of elapsed before they recovered completely.
the heart and respiratory rates were per- All animals were alive 7 mo after the last
formed in these two individuals). In Exper- experiment, but further clinical evaluation
iment 3, no signs of spontaneous recoYery or behavioral observations were not per-
were seen before injection of saline, but 35 formed.
min after medetomidine-ketamine injec-
tion, the corneal and pedal withdrawal re-
DISCUSSION
flexes were present in one animal, and the
corneal reflex was present in one other in- The medetomidine-ketamine combina-
dividual. tion in the dose range used in this study
The results from serial recordings of rapidly induced complete immobilization
physiologic measures are summarized in after i.m. administration in the pine marten.
Table 2. Except for the respiratory rate in Although most animals gained weight dur-
animals in Experiment l, a significant de- ing the study, the decrease in the mean doses
crease in the mean rectal temperature, heart of drugs did not significantly alter the mean
rate, and respiratory rate during immobi- induction times or the quality and degree
lization was seen in all animals in all ex- of immobilization. Immobilized animals
periments. The mean rectal temperatures were easily handled and did not react to
during Experiment 2 were significantly low- nociceptive stimuli (blood sampling). In all
er at all three recordings than during Ex- animals, both the corneal and pedal with-
periment I and than the two last recordings drawal reflexes were abolished for a period
in Experiment 3. There were no significant of time. In the dog, absence ofthese reflexes
differences in mean heart rate among ex- indicates light to deep surgical anesthesia,e
periments, and the mean respiratory rate and we therefore consider medetomidine-
during Experiment 2 was significantly lower ketamine to be a suitable anesthetic com-
552 .IOURNAL OF ZOO AND WILDLIFE MEDICINE

Table 3. Serum chemistry values in six captive pine martens (Martes martes) immobilized with medetomr-
dine-ketamine on three different occasions."

Expriment I Experiment 2 Experiment 3

Measure (Jul l99l) (Nov l99l) (Jan 1992)

AST (U/L) 159 (18) t21 (39) l 13 (20)

ALT (U/L) t73 (44) t72 (120) 222 (106)
cK (u/L) 5ss (234) 599 (616) 237 (2s1)
LDH (U/L) r,875 (520) r,244 (1t6)b 1,103 (129)
ALP (U/L) '17 (29) il5 (35) 85 (r6)
GGT (U/L) t7 (12) 25 (r9)
Amylase (U/L) 1,332 (20) 1,637 (29'7)b |,32t (242)
Lipase (U/L) 32 (i3) 39 (le) 35 (l 1)
Total protein (g/L) 6t (7) 60 (4) 62 (12)
Albumin (g/L) 30 (4) 37 (2) 35 (3)
Globulin (g/L) 3r (4) 23 (2) 26 (10)
Glucose (mmol/L) 17.3 (3.9) l 1.6 (0.8) t4.9 (4.3)
Cholesterol (mmol/L) 4.6 (0.6) 5.0 (0.5) 4.8 (0.5)
Triglycerides (mmol/L) 0.30 (0.08) 0.78 (0.69) 0.78 (0.24)
FFA (mmol/L) 0.s5 (0.19) 0.56 (0.62) 0.50 (0.0e)
Urea (mmol/L) l 1.3 (4.0) 8.2 (4.0) tz.t (4.9)
Creatinine (mmol/L) 70 (i6) 6l (13) 60 (5)
Total bilirubin (pmol/L) 1l (6) l0 (6)b 4 (2)
P (mmol/L) 1.6 (0.3) r-l (0.4) 0.9 (0.3)
Ca (mmol/L) 2.3 (0.4) 2.2 (0.r) 2.3 (0.1)
Mg (mmol/L) 0.81(0.12) 0.96 (0.04) 0.93 (0.09)
Na (mmol/L) 155 (3) 155 (l)b r 65 (3)
K (mmol/L) 4.0 (0.2) 3.8 (0.4) 3.9 (0.4)
Cl (mmol/L) r26 (l) 120 (3) 121 (4)

" Values are expressed as means (SD).

n
Superscript denotes a significant difference (P < 0.05) between means in Expriments 2 and 3

bination for minor surgical interventions in neous fat apparently is insufrcient to

pine martens.
The mean doses of medetomidine-ke-
tamine used in this study are higher than
those reported for any other carnivore spe-
cies. Preliminary studies (Arnemo, unpubl.
data) showed that the doses of medetomi-
dine-ketamine previously reported for
mustelids2't4'r7 and other furbearersr'r2'r4 were
inadequate for reliable immobilization of
captive pine martens. The doses necessary
to effectively immobilize Mrtes species us-
ing ketamine or xylazine-ketamine combi-
nations3'6'7'r0'20 are also relatively high com-
pared with those for other species.
There was a considerable drop in the mean
rectal temperature of the pine martens dur-
ing immobilization, but the hypothermic
response was most pronounced in the win-
ter experiments. Because seasonal insula-
tion provided by winter fur and subcuta-
counteract the effect of cold weather, the
rectal temperature of immobilized animals
should be monitored to detect severe drug-
induced hypothermia at low ambient tem-
peratures. The hypothermic effect of med-
etomidine-ketamine has also been reported
in raccoon dogs (Nyclereutes procyon-
oides),t mink(Mustela vison),2 and blue fox-
es (Alopex lagopus).t2In mink immobilized
with medetomidine-ketamine, normal
thermoregulation is restored after admin-
istration of atipamezole.2
The cardiovascular and respiratory re-
sponses to ketamine in clinically normal pa-
tients include an increase in heart and re-
spiratory rates.re However, in combination
with medetomidine both parameters de-
crease during immobilization in several
species.r'2,12'r4'2r In pine martens, there was
a significant drop in the mean heart rate in
 ARNEMO ET AL.-IMMOBILIZATION OF PINE MARTENS
all experiments and in the mean respiratory
rate in Experiments 2 and 3. In Experiment
1, the mean respiratory rate remained al-
most unchanged during immobilization.
Other cardiovascular or respiratory side ef-
fects were not detected clinically, and the
apneustic ketamine response reported for
some speciesr're'2r was not seen in our study.
Few significant differences in the mean
serum chemical values were found, and none
of them are considered to be of clinical im-
portance. Hyperglycemia, a well-known ef-
fect ofalphar-adrenoceptor agonists, is the
most prominent alteration in serum chem-
istry in animals immobilized with mede-
tomidine-ketamine.13 No baseline or ref-
erence values for serum chemistry in pine
martens are available, but the mean values
ofglucose found in our study are higher than
levels seen in other carnivores during med-
etomidine-ketamine immobilization.r2'r4
In our study, immobilization was rapidly
reversed after i.m. administration of ati-
pamezole. Because the duration of the ke-
tamine effect probably is unaffected by ati-
pamezole, the lower dose of ketamine in
Experiment 2 may have caused these ani-
mals to recover more quickly than did the
animals in Experiment l. All animals in Ex-
periments I and 2 showed signs of muscle
rigidity and incoordination for a period of
time after mobility was regained. Such ke-
tamine residual effects in animals immo-
bilized with medetomidine-ketamine may
be seen when atipamezole is given too early
or when high ketamine doses are used.la The
dose of ketamine used in the present study
was higher than the maximum doses rec-
ommended in mustelids and other carni-
vores.r3'ta In mink immobilized with med-
etomidine-ketamine, no such effects were
seen either after early reversal or when a
high ketamine dose was used.2 Atipamezole
is known to cause excitement when the dose
ratio of atipamezole relative to medetomi-
dine is too high,t2-'a and a dose ratio of 2-
3:1 has been recommended for carni-
vores.r3'l4 However, in our study no signs
of excitement were seen after a dose ratio
553
of 5:1. In mink2 and raccoon dogs,r dose
ratios of 5:l and l0:1, respectively, have
been used without causing any side effects.
In carnivores, the time taken for recovery
from medetomidine-ketamine immobili-
zalion varies among species: 20-30 min in
some small mustelids,ra approximately I hr
in blue foxesr2'r4 and mink,2 and 1.5-3 hr
in snow leopards (Panthera unica),tt'ta rac-
coon dogs,r and bears.ra Animals that were
given saline instead of atipamezole in our
study began to move 5l-99 min after ad-
ministration of medetomidine-ketamine.
The recoveries were characterized by pro-
longed sedation, incoordination, and motor
impairment. In two individuals, complete
recovery was not achieved until nearly 4 hr
after administration of medetomidine-ke-
tamine. We therefore recommend that pine
martens immobilized with medetomidine-
ketamine be given atipamezole to ensure a
faster and smoother recoYery.
CONCLUSIONS
Medetomidine-ketamine would be an ef-
fective combination for immobilization of
pine martens under field conditions because
induction is rapid after i.m. administration
and the drugs are potent and effective in a
small volume. Also, the duration and degree
of immobilizalion are sufficient for clinical
examination, biological sampling, and
medical procedures, and immobilization can
be successfully reversed with atipamezole.
Doses of 0.13-0.24 m{keof medetomidine
hydrochloride in combination with 6.5-1 1.8
milkg of ketamine i.m. were safe and ef-
fective in captive pine martens. Hypother-
mia, bradycardia, bradypnea, and pro-
longed recovery are potential complications,
and reversal with atipamezole hydrochlo-
ride at a dose ratio relative to medetomidine
hydrochloride of 5: I is recommended.
Acknowledgments: We thank the staffof Dal
Research Farm for assistance during the trials
and Orion Corp. Animal Health Division, Tur-
ku, Finland, lor their contribution of Domitoro
and Antisedan@.
554 JOURNAL OF ZOO AND WILDLIFE MEDICINE
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Receivedfor publication l0 November 1993