THE COMPUTED TOMOGRAPHIC ENHANCEMENT PATTERN OF THE NORMAL CANINE PITUITARY GLAND

Dynamic computed tomography (CT) of the pituitary gland was performed on four healthy male dogs of similar size, weight and age. The pituitary gland region was first identified on lateral scout and transverse non-contrast images. After localization, water soluble iodinated contrast medium was administered intravenously as a bolus at a dose of 1 ml/lb using a pressure injector at an injection rate of 10 ml/sec and a total of 40 post contrast images of the pitutary gland were acquired. No images were made after 400 seconds. The same pituitary region was imaged in each slice. The slice thickness was 1.5 mm, with a two second scan time and an eight second delay between images (resulting in images every ten seconds). The contrast medium injection and initial image were acquired simultaneously, resulting in a non-contrast enhanced initial image. At the completion of the CT scan, a region of interest (ROI) was drawn around the pituitary gland and time density data were obtained. The mean pituitary Hounsfield number was plotted as a function of time. A bi-exponential least squares model was used to derive the best fitting line through the data. The mean relative peak increase in pituitary Hounsfield Units (HU) was 65.9% +/- 2.1%. After the initial increase there was a decrease in pituitary Hounsfield number with a half-time of 16.1 seconds, followed by a slower phase with a half-time of 16.5 minutes. The mean pituitary gland HU value during the period of gradual opacity decline was 35.0% +/- 4.4% above that of the pre-contrast image. Establishing the enhancement pattern in the canine pituitary gland is the precursor to the clinical application of dynamic CT of the pituitary gland to diagnose pituitary microadenomas and/or small macroadenomas before they become exceptionally large.     

DYNAMIC COMPUTED TOMOGRAPHY OF THE NORMAL FELINE HYPOPHYSIS CEREBRI (GLANDULA PITUITARIA)

The purpose of this study was to describe normal feline hypophyseal mensuration and contrast enhancement characteristics using dynamic computed tomography (CT) imaging. An intravenous bolus of an ionic iodinated contrast medium was administered to eight cats using a pressure injector while dynamic CT images were obtained every 5 s for five cats and every 7 s for three cats for a total imaging time of 5 min. Each pituitary was measured at its maximum height and width on the peak contrast medium enhancement image. A hand-drawn region of interest was placed around each hypophysis cerebri and time attenuation curves were generated. The specific enhancement pattern of the hypophysis cerebri for each cat was recorded. The mean width and height of the hypophysis cerebri was 5.2 +/- 0.4 (average +/- SD) mm and 3.1 +/- 0.3 mm, respectively. The mean time to maximum contrast enhancement was 28.6 +/- 14.8 s (range 14-50 s) from the onset of contrast medium injection. Four cats had initial dorsal and peripheral contrast enhancement patterns of the hypophysis cerebri, while four cats had an initial central contrast medium enhancement pattern. The hypophysis cerebri had a homogenous appearance in all cats, 28-50 s after contrast medium injection. The average (+/- SD) clearance half-time was 292 (+/- 87) s. Normal hypophysis cerebri mensuration and contrast medium enhancement characteristics will help in clinical evaluation of the feline hypophysis cerebri.     

MENSURATION OF THE PITUITARY GLAND FROM MAGNETIC RESONANCE IMAGES IN 17 CATS

The objective of this retrospective study was to estimate using magnetic resonance imaging the size range of the pituitary gland in cats who had no evidence of pituitary disease. The pituitary gland was measured from transverse and sagittal magnetic resonance postgadolinium T1-weighted images in 17 cats. The cats were 0.83 to 15 years of age and weighed between 2.9 and 6.5 kg. Linear pituitary measurements were performed on a dedicated workstation using electronic calipers. Mean (+/- standard deviation) pituitary gland length was 0.54 cm (+/- 0.06 cm) and mean width was 0.50 cm (+/- 0.08 cm). Mean pituitary gland height measured on sagittal images was 0.34 cm (+/- 0.05) and measured on transverse images was 0.32 cm (+/- 0.04 cm). Mean pituitary volume was 0.05 cm3 (+/- 0.01 cm3). There was no significant correlation between cat weight (kg) and pituitary volume or age and pituitary volume. The pituitary gland appearance varied on pre- and postcontrast T1-weighted images. On the precontrast images, the majority of pituitary glands had a mixed signal intensity. On postcontrast images, uniform pituitary gland enhancement was seen commonly.     

DYNAMIC HELICAL COMPUTED TOMOGRAPHY OF THE PITUITARY GLAND IN HEALTHY DOGS

Dynamic helical computed tomography (CT) of the pituitary gland can be used to image the three-dimensional shape and dimensions of abnormalities within the pituitary gland. The aim of this study was to develop a protocol for dynamic helical CT of the pituitary gland in healthy dogs as a future reference study for patients with pituitary disease. Dynamic helical series of nine scans of the pituitary gland during and following contrast medium injection were performed in six healthy dogs using the following protocols: a series with 1 mm collimation and a table feed per X-ray tube rotation of 2 mm (pitch of 2) in six dogs, a series with 2 mm collimation and pitch of 2 in three dogs, and a series with 1 mm collimation and pitch of 1 in three other dogs. Multiplanar reconstructions of the images were made using a reconstruction index of 0.5. Images of all series were assessed visually for enhancement of the arteries, the neurohypophysis, and the adenohypophysis. The enhancement pattern of the neurohypophysis was distinguished adequately from that of the adenohypophysis in five dogs that were scanned with 1 mm collimation and pitch of 2, but the difference was less discernable when the other protocols were used. The carotid artery, its trifurcation, and the arterial cerebral circle were best visualized in dorsal reconstructions. Dynamic helical CT of the pituitary gland in healthy dogs can be performed with 1 mm collimation and pitch of 2, and a scan length that includes the entire pituitary region. Using this protocol, with the specific scanner used, the neurohypophysis, the adenohypophysis, and the surrounding vascular structures are adequately visualized.     

Dynamic computed tomographic evaluation of the pituitary gland in healthy dogs

OBJECTIVE: To determine the contrast enhancement pattern of the pituitary gland in healthy dogs via dynamic computed tomography (CT). ANIMALS: 17 dogs. PROCEDURE: With each dog in sternal recumbency, transverse CT scans were made perpendicular to the skull base from the rostral clinoid processes to the dorsum sellae. At the position of the image that contained the largest cross section of the pituitary gland, a series of 9 to 11 scans was made during and after IV injection of contrast medium (dynamic CT scans). The contrast enhancement pattern of the pituitary gland and surrounding arteries was assessed visually and by use of time-density curves. RESULTS: After strong enhancement of the maxillary arteries, the intracavernous parts of the internal carotid arteries, and the communicating arteries of the arterial cerebral circle, there was a strong enhancement of the central part of the pituitary gland followed by enhancement of its peripheral part. On the last images of the dynamic series of the pituitary gland, the central part was hypodense, compared with the peripheral part. Time-density curves confirmed an early, strong enhancement of the central part and a delayed, less strong enhancement of the peripheral part of the gland. CONCLUSIONS AND CLINICAL RELEVANCE: The difference in enhancement between the central and peripheral parts of the pituitary gland was attributable to a difference in vascularization of the neurohypophysis and adenohypophysis, respectively. Distortion or disappearance of the strong central enhancement (pituitary flush) may be used for the detection and localization of pituitary abnormalities in the adenohypophysis.     

Quantitative evaluation of contrast enhanced transcranial Doppler signal using galactose based echo-contrast agent in dogs

Transcranial Doppler ultrasonography (TCD) is hindered by insufficient ultrasound penetration through the temporal bone. The use of echo-contrast agents to enhance the Doppler signal is an important step toward the solution of this problem. The aim of the present study was to investigate the tolerability and diagnostic value of the intravenous echo-contrast agent, Levovist. Levovist was administered intravenously in 8 dogs with two doses (0.2 and 0.3 ml/kg) at different concentrations (300 and 400 mg/ml). In right middle cerebral artery (RMCA), the duration and degree of the signal enhancement were measured by TCD. All 32 administrations of Levovist produced an increase in TCD signal of the RMCA without complications. The first assessable pulse curve could be seen on the screen after 4 to 7 seconds after injection. There was no significant difference of latency period between different concentration and dosage. The signal amplitude was increased homogeneously by more than 30 dB when 0.3 ml/kg with 300 mg/ml concentration of Levovist and 0.2 and 0.3 ml/kg with 400 mg/ml concentration were administered. There was no significant difference in the duration of optimal contrasting between 0.3 ml/kg with 300 mg/ml concentration of Levovist and 0.2 and 0.3 ml/kg with 400 mg/ml concentration. The duration of the signal enhancement was 144 to 422 seconds, depending on the degree of concentration and dose of administration. Optimal TCD signal enhancement of RMCA was obtained using 0.3 ml/kg with 300 mg/ml concentration of Levovist in dogs, which is considered to provide quality visualization.     

MAGNETIC RESONANCE IMAGING CONTRAST ENHANCEMENT OF THE TRIGEMINAL NERVE IN DOGS WITHOUT EVIDENCE OF TRIGEMINAL NEUROPATHY

Brain magnetic resonance images from 42 dogs imaged between 2002 and 2007 were reviewed retrospectively to establish the incidence of trigeminal nerve contrast enhancement. These dogs had otherwise normal MR images and no clinical evidence of trigeminal nerve disease. Contrast enhancement of the entire trigeminal nerve was seen in 39 dogs and in the region of the trigeminal ganglion in all 42 dogs. When contrast enhancement of the trigeminal nerve was observed, the intensity was subjectively less than or equal to that of the pituitary gland. Contrast enhancement of the trigeminal nerve was seen in 42 dogs with no clinical evidence of trigeminal nerve pathology.     

Comparison of the time required to administer three different fluke and worm combination products to commercial beef cattle at housing

Larger livestock units, a decline in the farm labor force, animal welfare concerns, and a trend toward more selective use of drugs have increased the focus on animal handling, time management, convenience, and compliance in administering veterinary therapeutics. This study was undertaken to quantify and compare the time needed to treat commercial beef cattle with three fluke and worm combination products with different administration profiles. Young beef cattle (n = 270) weighing approximately 400 kg were allocated to batches of five, which were randomly assigned to receive ivermectin + clorsulon injection, ivermectin + closantel injection, or levamisole + triclabendazole oral drench. The mean time needed to administer ivermectin + clorsulon (single injection) to five cattle was 31 seconds, which was significantly less than the 100 seconds needed for ivermectin + closantel (two injections) and the 126 seconds needed for levamisole + triclabendazole (P less than .001). Such quantitative data can allow for better planning and selection of parasiticide treatment approaches at the farm level.     

Comparison of the effectiveness of ovulation synchronization protocol in anestrous and cycling beef cows

Applicability of ovulation synchronization protocol using GnRH and PGF(2alpha) (PGF) injection to anestrous beef cows remains controversial. We compared the effectiveness of the protocol in the anestrous stage of the beef cow with that in the cycling stage using the same animals. Ovaries of five Japanese Black and three Japanese Shorthorn cows were ultrasonographically examined, and blood samples were collected daily for hormonal analyses. Each animal received the protocol twice (Day -6 to -8: GnRH, Day 0: PGF, Day 2: GnRH). Additional blood samples were taken before and after GnRH injection for LH and FSH measurements to evaluate the pituitary function. For the ovarian status at the onset of the protocol cows were divided into anestrous (n=8) and cycling (n=8) stages. There was no significant difference in size of the dominant follicle at the first and second GnRH injections, and in the magnitude of the pituitary response to GnRH between the two stages. However, the size of the corpus luteum and progesterone concentrations at the PGF injection in the anestrous stage were significantly smaller and lower (P<0.01), respectively, and ovulation synchronization rate in the anestrous stage was significantly lower (P<0.05) than in the cycling stage. In conclusion, ovulation synchronization protocol in anestrous beef cows has limited effectiveness.     

USE OF COMPUTED TOMOGRAPHY AND RADIOLABELED LEUKOCYTES IN A CAT WITH PANCREATITIS

The normal feline pancreas has been evaluated using radiolabeled leukocytes (99mTc-HMPAO) and computed tomography. The purpose of this report is to describe a clinical case where both modalities were utilized to assess the inflamed feline pancreas. A nine year old female cat presented with anorexia, depression and some vomiting. Blood values were unremarkable. Radiographs and ultrasound were suggestive of pancreatitis. The cat's leukocytes were separated and labeled according to an established protocol. Whole body images were acquired immediately, at 5 and 30 min, and at 1, 2, 4, and 17 hours post injection. Approximately 48 h later, the animal was anesthetized and computed tomography of the abdomen was preformed both pre and post contrast. Surgical biopsies were taken. The distribution of the WBCs was similar to that documented in normal animals, however, at 2 h there was faint uptake seen in the region of the pancreas. This uptake became more intense at 4 h and persisted at 17 h. Computed tomography showed irregular margination of the pancreas, it was larger than normal and inhomogeneous. Contrast enhancement was inhomogeneous and its peak enhancement was not reached until 10 min post injection; normal feline pancreas enhances homogeneously and peaks immediately. Histopathology confirmed pancreatitis with lymphocytic, plasmacytic, neutrophilic and eosinophilic inflammation and fibrosis. Radiolabeled leukocytes can be used to document pancreatic inflammation and this is best seen 4 h after injection. Computed tomography allows superior visualization of the pancreas. Both the appearance and contrast enhancement pattern of the inflamed pancreas differ from normal.     

INTRAARTERIAL INJECTION OF IODINATED CONTRAST MEDIUM FOR CONTRAST ENHANCED COMPUTED TOMOGRAPHY OF THE EQUINE HEAD

Minimizing the volume of contrast administered for contrast‐enhanced computed tomography (CT) of the equine head is desirable for reducing costs and risks of adverse reactions, however evidence‐based studies on the effects of varying volumes on image quality are currently lacking. The objective of the current study was to determine whether low‐volume intraarterial administration of contrast medium would result in an equivalent image quality and tissue attenuation vs. high‐volume intravenous bolus administration. A prospective cross‐over experimental design was used in a sample of six horses. After anesthetic induction, the right carotid artery was exposed surgically and catheterized. Four CT scans of the cranium were performed for each horse: baseline, immediately following intraarterial contrast injection, five‐min postinjection (return to baseline) and a final scan after intravenous contrast administration. Soft tissue attenuation in predetermined regions of interest (ROI); and length, width, and height measurements of the pituitary gland were recorded at each time point. Horses were euthanized and measurements of the pituitary gland were repeated postmortem. No adverse reactions to contrast administration were observed. Intraarterial and intravenous administration of contrast medium resulted in significantly greater soft tissue enhancement of some brain ROI's and the pituitary gland vs. baseline values. Pituitary gland measurements made on postcontrast CT images did not differ from those obtained during postmortem examination. Findings indicated that low‐dose intraarterial administration of contrast material in the equine head resulted in comparable soft tissue enhancement vs. high volume intravenous administration.     

Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog

Ventilatory effects at induction of anaesthesia were studied following intubation in 66 dogs anaesthetised using thiopentone (10 mg/kg) or propofol (4 mg/kg, injected rapidly or 4 mg/kg, injected slowly). Acepromazine and morphine preanaesthetic medication was administered, and anaesthesia was maintained with halothane in nitrous oxide and oxygen. The time from connection of the breathing system to the first breath was measured. Apnoea was defined as cessation of spontaneous respiration for 15 seconds or longer. Respiratory rate and minute volume were measured for the first five minutes of anaesthesia. Propofol was associated with a greater incidence of apnoea than thiopentone (59 per cent and 64 per cent compared with 32 per cent), but this difference was not statistically significant. Time to first breath was significantly longer with propofol than thiopentone and longest with the slower injection of propofol (P<0.05) (median of four seconds for thiopentone, 19.5 seconds for the propofol rapid injection, and 28.8 seconds for the propofol slow injection). In conclusion, the induction agent and speed of injection affect the incidence and duration of post-intubation apnoea.     

Indirect magnetic resonance lymphography of the head and neck of dogs using Gadofluorine M and a conventional gadolinium contrast agent: A pilot study

The purpose of this pilot study was to evaluate lymph node enhancement with an indirect magnetic resonance (MR) lymphography technique using 2 different contrast agents in the head and neck region of healthy dogs. Five dogs were imaged at various times after intradermal injection of gadoversetamide and Gadofluorine M (minimum of 1 week apart) in the right and left mandibular, temporal, and lateral neck regions. We observed consistent progressive enhancement with time in the mandibular, retropharyngeal, and superficial cervical lymph nodes. The node enhancement was comparable for both contrast agents. Contrast enhancement of the parotid lymph nodes was not seen. We conclude that this technique of indirect MR lymphography using either agent could be used to identify those lymph nodes at highest risk of metastatic disease in dogs with cancer, and to guide staging and treatment.     

EFFECT OF DELAYED ACQUISITION TIMES ON GADOLINIUM‐ENHANCED MAGNETIC RESONANCE IMAGING OF THE PRESUMABLY NORMAL CANINE BRAIN

A delay in imaging following intravenous contrast medium administration has been recommended to reduce misdiagnoses. However, the normal variation of contrast enhancement in dogs following a delay has not been characterized. Contrast‐enhanced MR imaging of 22 dogs was assessed, in terms of identification of normal anatomic structures, to investigate the variation associated with 10‐min delay between contrast medium administration and imaging. All dogs had a normal brain MR imaging study and unremarkable cerebrospinal fluid. Specific regions of interest were assessed both objectively, using computer software, and subjectively using three observers. Mean contrast enhancement >10% was seen in the pituitary gland, choroid plexus, meninges, temporal muscle, trigeminal nerve, and the trigeminal nerve root. Structures with an active blood–brain barrier had minimal contrast enhancement (<6%). Enhancing structures had significantly more contrast enhancement at t=1 min vs. t=10 min, except in temporal muscle, the trigeminal nerve and the trigeminal nerve root. Interobserver agreement was moderate to good in favor of the initial postcontrast T1‐weighted (T1w) sequence. The observers found either no difference or poor agreement in identification of the nonvascular structures. Intraobserver agreement was very good with all vascular structures and most nonvascular structures. A degree of meningeal enhancement was a consistent finding. The initial acquisition had higher enhancement characteristics and observer agreement for some structures; however, contrast‐to‐noise was comparable in the delayed phase or not significantly different. We provide baseline references and suggest that the initial T1w postcontrast sequence is preferable but not essential should a delayed postcontrast T1w sequence be performed.     

The desmopressin stimulation test in dogs with Cushing's syndrome

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.     

Pituitary responsiveness to GnRH, hypothalamic content of GnRH and pituitary LH and FSH concentrations immediately preceding puberty in gilts

To determine whether pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) or hypothalamic content of gonadotropin releasing hormone (GnRH) change before puberty, 40 prepubertal gilts averaging 7 mo of age were slaughtered before or on the second, third or fourth day after relocation and boar exposure. Some gilts responded to relocation and boar exposure as indicated by swollen vulvae, turgid uteri and enlarged ovarian follicles at the time of slaughter. Pituitary concentrations of LH and FSH and hypothalamic content of GnRH were similar between gilts that responded to relocation and boar exposure and gilts that did not respond. In addition, boar exposure and relocation had no effect on pituitary concentrations of LH and FSH or on hypothalamic content of GnRH. To determine whether pituitary responsiveness to GnRH changes before puberty, a third experiment was conducted in which 72 gilts were injected with 400 micrograms of GnRH either before or on the second, third or fourth day after relocation and boar exposure. In gilts that subsequently responded (i.e., ovulated) as a result of relocation and boar exposure, pituitary responsiveness to GnRH was reduced as compared with gilts that failed to ovulate after relocation and boar exposure. Peak concentrations of serum LH after GnRH injection were 4.6 +/- 1.3 vs 9.8 +/- .8 ng/ml for responders vs nonresponders. Peak serum FSH after GnRH injection was also lower for responders than for nonresponders (29.5 +/- 4.2 vs 41.2 +/- 2.4 ng/ml). When compared with controls, relocation and boar exposure did not significantly affect GnRH-induced release of LH and FSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analgesic and spasmolytic effects of dipyrone, hyoscine-N-butylbromide and a combination of the two in ponies.

The analgesic and spasmolytic effects of dipyrone (Novalgin) (2500 mg/100 kg bodyweight) hyoscine-N-butylbromide (Buscopan) (20 mg/100 kg bodyweight) and a combination of both drugs were evaluated in a balloon-induced model of colic, using five ponies with caecal fistulae. The drugs were given intravenously and 0.9 per cent sodium chloride solution (5 ml/100 kg bodyweight) was used as a control. The physiological saline solution and dipyrone had no effect on caecal contractions. After the injection of hyoscine-N-butylbromide and the drug combination caecal contractions ceased within 30 seconds and for 20 and 24 minutes, respectively (P less than 0.05). The results on pain relief were not statistically significant for any of the drugs. Dipyrone had a good analgesic effect in only two of the ponies, starting after eight to 10 minutes and lasting for 50 minutes. The drug combination relieved pain within 30 seconds after injection and the relief lasted for 50 minutes in three of the ponies and for 20 minutes in the other two. Hyoscine-N-butylbromide alone produced an analgesic effect within 30 seconds after injection which lasted for 20 minutes.     

Cardiovascular and respiratory effects of three rapidly acting barbiturates in dogs

The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (SV) decreased; heart rate (HR), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (CI), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (MAP) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except HR had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values. Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, MAP decreased at 15 seconds, and SV decreased at all measurement times.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of optimal immobilizing doses of a medetomidine hydrochloride and ketamine hydrochloride combination in captive reindeer

OBJECTIVE: To establish optimal immobilizing doses of medetomidine hydrochloride (MED) with ketamine hydrochloride (KET) for hand- and dart-administered injections in captive reindeer. ANIMALS: 12 healthy 6- to 9-month-old reindeer (Rangifer tarandus tarandus). Procedure An optimal dose was defined as a dose resulting in an induction time of 150 to 210 seconds, measured from the time of IM injection until recumbency. Initially, each stalled reindeer was immobilized by hand-administered injection. If the induction time was > 210 seconds, the dose was doubled for the next immobilization procedure. If it was < 150 seconds, the dose was halved for the next immobilization procedure. This iteration procedure was continued for each reindeer until an optimal dose was found. Later the reindeer was placed in a paddock and darted with its optimal dose as determined by hand-administered injection. Adjusting to a linear relationship between dose and induction time, optimal darting doses for each reindeer were predicted and later verified. RESULTS: The established mean optimal hand- and dart-administered doses were 0.10 mg of MED/kg of body mass with 0.50 mg of KET/kg, and 0.15 mg of MED/kg with 0.75 mg of KET/kg, producing mean induction times of 171 seconds and 215 seconds, respectively. The mean induction time after darting was 5 seconds greater than the upper limit of the predefined time interval. CONCLUSIONS AND CLINICAL RELEVANCE: The higher dose requirement of MED-KET administration outdoors, compared with indoors, was explained by factors inherent in the darting technique and the different confinements. The iteration and the prediction methods seem applicable for determination of optimal doses of MED-KET in reindeer. The iteration and the prediction procedures may be used to reduce the number of experimental animals in dose-response studies in other species.