Persistent changes in arterial blood gases in fetal sheep

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.     

Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep

Chorioamnionitis is an antecedent of preterm birth. We aimed to determine the effect of experimental chorioamnionitis in fetal sheep during late gestation on 1) nephron number, 2) renal corpuscle volume, and 3) renal inflammation. We hypothesized that exposure to chorioamnionitis would lead to inflammation in fetal kidneys and adversely impact on the development of nephrons, leading to a reduction in nephron number. At ～121 days of gestation (term ～147 days), pregnant ewes bearing twin or singleton fetuses received a single intra-amniotic injection of lipopolysaccharide (n = 6; 3 singletons, 3 twins); controls were either untreated or received an intra-amniotic injection of saline (n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At ～128 days of gestation, fetuses were delivered via Caesarean section. Kidneys were collected and stereologically analyzed to determine nephron number and renal corpuscle volume. Renal inflammation was assessed using immunohistochemistry. Experimental chorioamnionitis did not affect body weight or relative kidney weight. There was a significant reduction in nephron number but no change in renal corpuscle volume in LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18% in singleton and twin LPS-exposed fetuses, respectively. The degree of renal inflammation did not differ between groups. Importantly, this study demonstrates that exposure to experimental chorioamnionitis adversely impacts on nephron number in the developing fetus.     

Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 +/- 7.7 h (mean +/- SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20 alpha-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11-13 days). Maternal plasma progesterone and 20 alpha-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20 alpha-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.     

Sheep model for study of maternal adrenal gland function during pregnancy

Our goal was to develop a model for the study of maternal adrenal gland regulation and the effects of maternal cortisol secretion on fetal homeostasis. At about 108 days of gestation, before the time of rapid fetal growth or fetal adrenocortical maturation, ewes, under halothane anesthesia with controlled ventilation and positioned in sternal recumbency, were adrenalectomized. Ewes were treated with aldosterone by intravenous infusion (3 micrograms/kg of body weight per day) to induce normal late-gestation aldosterone concentration. Ewes were also treated with cortisol; for 2 postoperative days, this infusion (1 to 2 micrograms/kg per min) induced plasma concentration similar to that associated with stress. Thereafter, the dosage of cortisol was reduced to induce plasma values similar to normal late-gestation cortisol concentration in ewes (1 mg/kg per day), or to values in nonpregnant ewes (0.6 mg/kg per day). Administration of cortisol and aldosterone was required to prevent electrolyte imbalance and signs of hypoadrenocorticism. With steroid replacement, plasma protein, electrolyte, and glucose concentrations in adrenalectomized ewes were not different from those in sham-operated pregnant ewes. Of 11 adrenalectomized ewes, one died as a result of failure of the infusion pump, and one died as a result of inappropriate treatment for hypoglycemia. Of the remaining ewes, two aborted fetuses, three ewes each delivered one live and one dead fetus, two delivered live singleton fetuses, and two delivered twins. Therefore, this model of relative hypoadrenocorticism in pregnancy is feasible and practical for studying the influence of maternal cortisol concentration on maternal and fetal homeostasis.     

Susceptibility to Pregnancy Disease in Ewes and its Relation to Gestastional Diabetes

The ability of 8 pregnant ewes to maintain glucose homeostasis following an intravenous glucose load (glucose tolerance test) and during starvation in late pregnancy was studied. Following an intravenous load 2 out of 7 ewes tested showed an impaired insulin secretion during the first 10–15 min. An increase in plasma insulin concentration was found 50–60 min after the injection. The results of the effect of a starvation on a number of blood constituents are demonstrated. Two of the twin–pregnant ewes developed symptoms of pregnancy disease following starvation, these were the same ewes that showed an impaired insulin secretion after the glucose load. However, no difference was demonstrated in the clinical chemical parameters whether the experimental ewes developed pregnancy disease or not.     

Comparison of intravenous medetomidine and medetomidine/ketamine for immobilization of free-ranging variable flying foxes (Pteropus hypomelanus)

Medetomidine (0.03 mg/kg) and medetomidine/ketamine (0.05/5.0 and 0.025/2.5 mg/kg), administered by intravenous injection, were evaluated for short-term immobilization of wild-caught variable flying foxes (Pteropus hypomelanus). Medetomidine alone produced incomplete chemical restraint and a stressful, prolonged induction. Both ketamine/medetomidine doses produced a smooth induction and complete immobilization. The combined medetomidine/ketamine dose of 0.025/2.5 mg/kg produced a rapid induction (232±224 sec) with minimal struggling and vocalization, a complete and effective immobilization period, and tended to lead to a faster and better quality recovery than medetomidine alone or a higher dose of medetomidine and ketamine (0.05/5.0 mg/kg), thus reducing holding time and permitting an earlier release of the bat back into the wild.     

Indomethacin reversal of ethanol-induced suppression of ovine fetal breathing movements and relationship to prostaglandin E2

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P less than 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P less than 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P less than 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P greater than 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats

Two groups of rats were anaesthetized at weekly intervals for 6 weeks with either ketamine/medetomidine alone (60 mg/0.4 mg/kg i.p.) or ketamine/medetomidine (45 mg/0.3 mg/kg i.p.) one hour following buprenorphine (0.05 mg/kg s.c.). Animals that received buprenorphine had longer periods of surgical anaesthesia (P = 0.04) and a greater depression of both mean pedal withdrawal score (P < 0.01) and mean respiratory rate (P = 0.014). Mean total duration of anaesthesia was also greater in the buprenorphine group on day 1. Sleep times reduced with successive doses of anaesthetic in the buprenorphine group (P = 0.024). Two animals in the buprenorphine group died. Repeated anaesthesia with ketamine/medetomidine alone was not associated with anaesthetic mortality. These results indicate that although buprenorphine has a clear anaesthetic-sparing effect, its use with ketamine/medetomidine may be associated with an increased risk of anaesthetic-related mortality.     

Short duration anaesthesia with medetomidine and ketamine in cynomolgus monkeys

Cynomolgus monkeys were anaesthetized with either intramuscular ketamine (10 mg/kg or intramuscular ketamine 2 mg/kg and medetomidine 50 microg/kg. Various physiological measurements were made once the animals were safe to handle and again 10 min later. Cardiovascular and respiratory function were well maintained with both regimens but the heart rate was lower and arterial-alveolar carbon dioxide gradient was higher in the animals that received medetomidine. In those animals that received medetomidine, atipamezole was given to reverse the medetomidine but there was no difference in recovery times between the two regimens. Anaesthesia was not entirely reliable with medetomidine/ketamine and we recommend caution when using this mixture.     

The Effects of Pregnancy and Feeding on the Insulin and Glucose Concentrations in Blood of Ewes in Late Pregnancy

In 8 experimental ewes on normal diet the influence of pregnancy and feeding on insulin and glucose in the blood was studied. A reduction in insulin concentration was found as pregnancy advanced. Blood glucose fluctuated, but during late pregnancy the blood glucose level was significantly lower in twin–pregnant ewes than in ewes pregnant with 1 fetus. No increase in insulin concentration was demonstrated in twin–pregnant ewes after feeding, on the contrary an increase was found in ewes pregnant with 1 fetus. A limited effect of feeding on the glucose concentration was observed, especially compared to the reference range. A positive correlation was obtained between the concentration of glucose and insulin in the blood.     

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.     

Immobilization of sika deer with medetomidine and ketamine, and antagonism by atipamezole

Forty wild sika deer (Cervus nippon) were immobilized with medetomidine and ketamine and reversed by atipamezole in summer and fall captures from September 1994 to October 1995. For large yearling and older deer, mean +/- SD doses of 57.0+/-15.6 microg/kg medetomidine and 1.64+/-0.49 mg/kg (male) or 4.02+/-1.16 mg/kg (female) of ketamine were administered by intramuscular injection. For calves and small yearlings, 69.3+/-7.0 microg/kg medetomidine and 2.69+/-0.44 mg/kg ketamine were administered. While immobilized, deer were easy to handle, and muscles were well relaxed. After intramuscular administration of atipamezole (about 5 times the dose of medetomidine), deer recovered rapidly and smoothly.     

Impact of periconceptional nutrition on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies

It has been proposed that maternal nutrient restriction may alter the functional development of the adipocyte and the synthesis and secretion of the adipocyte-derived hormone, leptin, before birth. We have investigated the effects of restricted periconceptional undernutrition and/or restricted gestational nutrition on fetal plasma leptin concentrations and fetal adiposity in late gestation. There was no effect of either restricted periconceptional or gestational nutrition on maternal or fetal plasma leptin concentrations in singleton or twin pregnancies during late gestation. In ewes carrying twins, but not singletons, maternal plasma leptin concentrations in late gestation were directly related to the change in ewe weight that occurred during the 60 days before mating [maternal leptin = 0.9 (change in ewe weight) + 7.8; r = 0.6, P < 0.05]. In twin, but not singleton, pregnancies, there was also a significant relationship between maternal and fetal leptin concentrations (maternal leptin = 0.5 fetal leptin + 4.2, r = 0.63, P < 0.005). The relative mass of perirenal fat was also significantly increased in twin fetal sheep in the control-restricted group (6.0 +/- 0.5) compared with the other nutritional groups (control-control: 4.1 +/- 0.4; restricted-restricted: 4.4 +/- 0.4; restricted-control: 4.3 +/- 0.3). In conclusion, the impact of maternal undernutrition on maternal plasma leptin concentrations during late gestation is dependent on fetal number. Furthermore, we have found that there is an increased fetal adiposity in the twins of ewes that experienced restricted nutrition throughout gestation, and this may be important in the programming of postnatal adiposity.     

Lack of maternal to fetal transfer of 125I-labelled erythropoietin in sheep.

We administered tracer quantities of biologically active 125I-labelled recombinant human erythropoietin by intravenous bolus injection to seven late gestation pregnant ewes. Maternal and fetal blood was sampled over the subsequent six hours and assayed for erythropoietin-specific radioactivity. Despite the expected increase in maternal plasma immunoprecipitable 125I-labelled erythropoietin radioactivity, fetal plasma levels remained unchanged throughout the study. In addition, erythropoietin receptors were not detected in ovine and human placental tissue. We conclude that biologically active 125I-labelled erythropoietin does not cross the placenta from mother to fetus in measurable quantities in sheep, and likely in humans. Thus, these data indicate the levels of erythropoietin measured in fetal plasma are reflective of fetal, and not maternal, erythropoietin production and elimination.     

Myometrial activity and plasma progesterone and oxytocin concentrations in cycling and early-pregnant ewes

Myometrial activity and plasma progesterone (P) and oxytocin (OT) were measured in early pregnant (n = 5) and cycling (n = 5) ewes. Electromyography (EMG) leads and jugular and inferior vena cava (IVC) catheters were surgically placed in ewes about 1 wk before data collection. When ewes returned to estrus, they were bred to either an intact or vasectomized ram. Continuous EMG data were collected, and blood samples were collected twice daily from day of estrus (Day 0) until Day 18. Ewes bred with an intact ram were checked surgically for pregnancy on Day 20. Computerized, quantitative analysis of EMG events showed no difference in signal from the right to left uterine horns, and no differences between pregnant and cycling ewes (p less than 0.05) until Days 14-18 when nonpregnant ewes returned to estrus and had increased EMG activity. The mean number of EMG events 180-900 s in length decreased in pregnant ewes, but this difference was not significant (p less than 0.05). Jugular plasma progesterone (P) levels confirmed corpus luteum (CL) formation in all ewes, and no differences in P between pregnant and nonpregnant ewes were measured until Days 14-18, when cycling ewes underwent luteolysis and pregnant ewes maintained CL. IVC plasma oxytocin concentrations were increased in pregnant ewes compared to concentrations in nonpregnant ewes on Days 5-13 (p less than 0.05), and the difference was largest at Day 6 (means +/- SEM pg/ml: pregnant = 68.7 +/- 13.9, nonpregnant = 30.9 +/- 19.9).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutritional challenges during development induce sex-specific changes in glucose homeostasis in the adult sheep

The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced (P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.     

Effect of post-mating GnRH analogue (buserelin) treatment on PGF2alpha release in ewes and ewe lambs

The objectives of this study were to determine the effects of buserelin or saline treatment on ovarian function (Experiment 1), plasma PGFM concentrations and oxytocin stimulated prostaglandin F(2alpha) (PGF(2alpha)) release (Experiment 2) in ewe lambs and ewes. Welsh Halfbred ewes (n=26) and ewe lambs (n=24) were mated to vasectomised rams at synchronised oestrus and on Day 12 post-mating each animal was injected intramuscularly either normal saline or 4 microg buserelin. In Experiment 1, plasma progesterone and oestradiol concentrations were determined in samples collected by jugular venepuncture 1h before and at 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment (n=7 per treatment group). Progesterone concentrations increased (P<0.05) from 2 to 8h after buserelin treatment and returned to basal levels after 72 h, whereas oestradiol concentrations were maximal at 2h post-treatment and returned to basal levels after 24h (P<0.05). Oestradiol concentrations were lower (P<0.05) in buserelin-treated animals than controls at 72 h post-treatment. Basal and post-treatment progesterone concentrations were greater (P<0.05) in ewes than in ewe lambs but oestradiol levels were similar for both age groups. Ovulation rate, determined by laparoscopy on Day 14, was similar for both age groups (ewes 1.1; ewe lambs 1.0). Buserelin treatment induced accessory corpora lutea in ewes (4/7; 57%) but not in ewe lambs (0/7; 0%). In the Experiment 2, plasma PGFM concentrations were determined in samples collected at 20-min intervals for 6h on Day 14 and at 20-min intervals for 1h before and at 10-min intervals for 1h and then at 20-min intervals for a further 3h period after an intravenous injection of oxytocin (1IU/kg body weight) on Day 15 post-oestrus. In this experiment there were five ewe lambs and six ewes per treatment group. There was no effect of buserelin treatment or age on basal PGFM concentrations on either Day 14 or 15. Although peak PGFM concentrations tended to be lower in buserelin-treated animals, the difference was not significant (P>0.05). However, peak duration following oxytocin challenge on Day 15 post-mating was shorter (P<0.05) in control ewes compared with control ewe lambs. In conclusion, buserelin treatment given on Day 12 post-oestrus enhances luteal function more in ewes than ewe lambs and after a transitory increase, reduces oestradiol concentrations in both ewes and ewe lambs. However, buserelin treatment does not significantly attenuate the luteolytic signal.     

Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep

The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n?=?10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n?=?10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81?mg arginine/kg?body?weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.     

Immobilization of California sea lions using medetomidine plus ketamine with and without isoflurane and reversal with atipamezole

The use of medetomidine and ketamine, alone and in combination with isoflurane, with atipamezole reversal was evaluated for immobilizing 51 California sea lions (Zalophus californianus) for a variety of medical procedures at a rehabilitation center in northern California (USA) between May 1997 and August 1998. Animals were given 140 microg/kg medetomidine with 2.5 mg/kg ketamine intramuscularly. Mean (+/-SD) time to maximal effect was 8+/-5 min. At the end of the procedure, animals were given 200 microg/kg atipamezole intramuscularly. Immobilization and recovery times were, respectively, 25+/-12 and 9+/-7 min for 35 animals maintained with medetomidine and ketamine alone and 58+/-30 and 9+/-9 min for 16 animals intubated and maintained with isoflurane. No mortalities occurred as a result of the immobilizations. Disadvantages of the medetomidine and ketamine combination included a moderate variation in time to maximal effect and plane of sedation, a large injection volume and high cost. However, this combination offers safe and reversible immobilization that can be easily administered by the intramuscular route and that produces a plane of anesthesia that is sufficient to carry out most routine diagnostic procedures.     

Effective immobilizing doses of medetomidine-ketamine in free-ranging, wild Norwegian reindeer (Rangifer tarandus tarandus)

Combinations of medetomidine and ketamine were evaluated in free-ranging, wild Norwegian reindeer (Rangifer tarandus tarandus) as part of a reintroduction program in southwestern Norway in November 1995 and November 1996. The drugs were administered by dart from a helicopter. The mean (SD) effective immobilizing doses for 29 adults (8 males, 21 females) were 0.21 (0.04) mg medetomidine/kg and 1.0 (0.2) mg ketamine/ kg based on estimated body mass. There was no significant difference in mean induction times between males and females. However, animals with optimal hits (shoulder or thigh muscles; n=16) had a significantly shorter (P<0.05) mean induction time than did animals with suboptimal hits (abdomen or flank; n=13), 5.6 (2.2) min and 11.1 (4.7) min, respectively. Inductions were calm, and immobilized animals were maintained in sternal recumbency. Clinical side effects included hypoxemia and hyperthermia in most animals. For reversal, all animals received 5 mg atipamezole per mg medetomidine, half intravenously and half intramuscularly, and the mean (SD) time to standing was 3.7 (3.6) min.