Hepatic lesions in 90 captive nondomestic felids presented for autopsy.

Hepatic lesions in nondomestic felids are poorly characterized. The purpose of this study was to evaluate hepatic lesions in 90 captive, nondomestic felids including tigers, cougars, and lions. Hepatic lesions were histologically characterized as vacuolar change (lipidosis or glycogenosis), biliary cysts, biliary hyperplasia, hepatitis, necrosis, neoplasia, fibrosis, veno-occlusive disease, cholestasis, hematoma, congestion, or hemorrhage. Stepwise logistic regression analyses were performed for vacuolar change, benign biliary lesions, hepatitis, lipogranulomas, extramedullary hematopoiesis, and hepatic stellate cell hypertrophy and hyperplasia, with species as the outcome variable. Ninety cats met the inclusion criteria. Seventy livers (78%) contained 1 or more lesions. Hepatocellular vacuolar change (41/90 [46%]) was the most common lesion overall. Extramedullary hematopoiesis, lipogranulomas, and hepatic stellate cell hyperplasia were also common. One snow leopard had veno-occlusive disease. Tigers were more likely than other felids to have no significant hepatic histologic lesions (odds ratio [OR], 12.687; P = .002), and lions were more likely to have biliary cysts (OR, 5.97; P = .021). Six animals (7%) died of hepatic disease: cholangiocellular carcinoma (n = 2) and 1 each of hepatic lipidosis, hepatocellular necrosis, pyogranulomatous hepatitis, and suppurative cholecystitis. Hepatocellular iron and copper accumulations were present in 72 of 90 (80%) and 10 of 90 (11%) sections, respectively. Sinusoidal fibrosis was common (74/90 [82%]) and primarily centrilobular (65/74 [88%]). Hepatocellular iron, copper, and fibrosis were not significantly associated with hepatic lesions. Primary hepatic disease was not a common cause of death in nondomestic felids in this study.

Renal lesions of nondomestic felids.

To comprehensively evaluate the occurrence of renal lesions in a variety of nondomestic felids, necropsy cases from 1978 to 2008 were reviewed from a municipal zoo and a large cat sanctuary for those in which the kidneys were examined histologically. Seventy exotic felids were identified (25 tigers, 18 lions, 6 cougars, 5 leopards, 3 snow leopards, 3 clouded leopards, 3 Canadian lynx, 2 ocelots, 2 bobcats, 2 cheetahs, 1 jaguar), and their histologic renal lesions were evaluated and compared. The most common lesion was tubulointerstitial nephritis (TIN); 36 of 70 (51%) cats were affected to some degree. Lymphocytic interstitial nephritis was the most common lesion in the tigers (9 of 25, 36%) and was rarely seen in other species. Although the renal pelvis was not available for all cats, 28 of 47 (60%) had some degree of lymphocytic pyelitis. There was no significant association between the presence of pyelitis and that of TIN. Only 1 cat had pyelonephritis. Renal papillary necrosis was present in 13 of 70 (19%) cats and was significantly associated with historical nonsteroidal anti-inflammatory drug treatment (odds ratio, 7.1; 95% confidence interval, 1.9 to 26.8). Only 1 cat (lion) had amyloid accumulation, and it was restricted to the corticomedullary junction. Primary glomerular lesions were absent in all cats. Intraepithelial pigment was identified in many of the cats but was not correlated with severity of TIN. Despite several previous reports describing primary glomerular disease or renal amyloidosis in exotic felids, these lesions were rare to absent in this population.

Cervical necrotizing fasciitis and myositis in a western lowland gorilla (Gorilla gorilla gorilla).

A 39-yr-old wild-caught, female western lowland gorilla (Gorilla gorilla gorilla) died during an immobilization to assess swelling and apparent pain of the cervical region. Necropsy revealed a fistulous tract containing plant material in the oropharynx, above the soft palate, communicating with a left-sided cervical necrotizing fasciitis and myositis. Alpha-hemolytic Streptococcus and Prevotella sp. were isolated from the cervical lesion. This is a report of cervical necrotizing fasciitis in a western lowland gorilla.

Neoplasia in Captive Panthera Species.

This retrospective study identified the spectrum of neoplasia diagnoses, prevalence rates and the contribution of neoplasia to death or humane destruction within Panthera species housed at a large cat sanctuary. Biopsy and necropsy reports from January 2002 to December 2017 were examined and histological material from cases diagnosed with neoplasia was reviewed. One hundred and sixty-eight neoplasms were diagnosed in 108 large felids: 70 tigers (Panthera tigris), 26 lions (Panthera leo), three ligers (P. leo × P. tigris), eight leopards (Panthera pardus) and one jaguar (Panthera onca). Forty-four felids had multiple neoplasms. The overall neoplasia rate (animals with neoplasms/all Panthera spp. pathology accessions) was 50.2%. Neoplasms predominantly originated from the reproductive (n = 47), endocrine (n = 27) and integumentary (n = 24) systems, with mammary carcinoma the most common neoplasm (n = 28). Mammary carcinomas comprised 59.6% of the reproductive tumours diagnosed and commonly metastasized widely. Neoplasia was the cause of death or humane destruction in 50.9% of the animals diagnosed with neoplasms. All lymphomas (n = 16) were responsible for death or humane destruction. This study shows that malignant and benign neoplasms are present in approximately half of ageing, captive Panthera spp., and that half of these animals will die or be humanely destroyed as a result of their neoplasms.

A lipid-based delivery system for antisense oligonucleotides derived from a hydrophobic complex.

Antisense oligodeoxynucleotides (ASOs) prevent expression of proteins by binding to specific regions of mRNA. This report investigates a potential lipid-based delivery system for ASO. A hydrophobic complex was recovered following addition of cationic lipids to ASOs in a Bligh and Dyer monophase [chloroform/methanol/water (1:2.1:1, v/v/v)]. The addition of monovalent cationic lipids (dioleyldimethylammonium chloride, dimethyldioctadecylammonium bromide, dioleoyltrimethylammonium propane), resulted in > 95% recovery of the ASOs from the organic phase when ASO phosphate charge was neutralized. Cholesteryldimethylaminoethylcarbamate mediated efficient extraction at a charge ratio (+/-) > 5.2. ASOs could not be extracted into the organic phase by the polyvalent lipids, dioctadecylamidoglycyl spermine and 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propaminium trifluoroacetate, even at a charge ratio (+/-) > 5. Dioleoylphosphatidylethanolamine, but not dioleoylphosphatidylcholine, prevented formation and destabilized the hydrophobic complexes. The characterization of the hydrophobic complex led to the development of lipid-ASO particles containing dioleyldimethylammonium chloride, dioleoylphosphatidylethanolamine and poly(ethylene glycol)-conjugated phosphatidylethanolamine (LAPs). When FITC-labeled ASOs in LAPs were added to B-cell lymphoma cells (DoHH2) in vitro, cell-associated ASO decreased as poly(ethylene glycol)-conjugated phosphatidylethanolamine incorporation increased. Western Blot analysis demonstrated that no significant downregulation of Bcl-2 protein was observed when using LAPs. The results suggest that the use of stabilized PEG-conjugated lipids may be detrimental for cationic lipid-based ASO delivery.

Phosphatidylethanolamine mediated destabilization of lipid-based pDNA delivery systems.

We have previously reported the development of lipid-DNA particles (LDPs) formed, via a hydrophobic cationic lipid-DNA complex intermediate, when detergent-solubilized cationic lipids are mixed with DNA. This study investigates the influence of zwitterionic co-lipid headgroups on the formation and stability of this intermediate and the subsequent DNA protection and transfection properties afforded by the resultant LDPs. We report that inclusion of diacylphosphatidylethanolamines (diacylPE), but not diacylphosphatidylcholines (diacylPC), as co-lipids destabilizes and prevents the formation of the cationic lipid-DNA intermediate to an extent dependent on the concentration of diacylPE and its acyl chain characteristics. DNA formulated in LDPs containing cationic:zwitterionic lipids at a 1:1 ratio is not readily accessible to the intercalating fluorescent dye, TO-PRO-1. At a lipid ratio 1:4, diacylPC LDPs are associated with significantly greater TO-PRO-1 fluorescence than equivalent diacylPE formulations, a result believed to reflect lipid-dependent penetration of TO-PRO-1 through the supramolecular LDP assembly, rather than condensation and protection of the DNA per se. Transfection studies utilizing the in vitro murine B16/BL6 melanoma cell line and the in vivo intraperitoneal B16/BL6 mouse tumor model demonstrated that only diacylPE LDPs mediated gene transfer. This was found not to be a consequence of differences in DNA delivery or cell toxicity.

Pharmacokinetic properties of gentamicin and amikacin in the cockatiel.

Gentamicin and amikacin are commonly used in veterinary medicine to treat a variety of gram-negative bacterial infections. The present study evaluates the pharmacokinetics of gentamicin sulfate and amikacin sulfate in the cockatiel (Nymphicus hollandicus), a small (approximate body weight = 100 g) psittacine bird, utilizing treatment regimens developed in larger parrot species. Serum antibiotic concentrations were determined in cockatiels following twice-daily intramuscular treatment with 5 mg gentamicin/kg body weight and 15 mg amikacin/kg body weight. In the present study, peak values of gentamicin were 4.6 +/- 1.45 micrograms/ml, and trough values were 0.17 +/- 0.04 micrograms/ml. Amikacin administration resulted in peak values of 27.3 +/- 6.9 micrograms/ml and trough concentrations of 0.9 +/- 0.3 micrograms/ml. Based on the present study, an appropriate intramuscular dose regimen for gentamicin in cockatiels is 5 to 10 mg/kg body weight either two or three times per day. An intramuscular amikacin dosage of 15 to 20 mg/kg body weight either two or three times per day is recommended for treatment of infections caused by susceptible bacteria.

Tissue and serum enzyme activities in the yellow rat snake (Elaphe obsoleta quadrivitatta).

Activities of diagnostically important enzymes were measured in serum and lysates of liver, kidney, skeletal muscle, heart, intestine, lung, and pancreatic tissues from wild-caught yellow rat snakes, Elaphe obsoleta quadrivitatta. All samples were analyzed for alkaline phosphatase, lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase, gamma-glutamyltransferase, and creatine kinase (CK) activities. The major enzyme activities found in the liver were LD and AST. The kidney had moderate activities of LD, AST, alanine transaminase, and CK. Skeletal muscle and heart contained high CK activity. Intestine, lung, and pancreas had low activities for most enzymes analyzed. Little to no gamma-glutamyltransferase activity was found in serum or tissues analyzed. Serum enzyme activities in yellow rat snakes were similar to those described for other reptile species, except for serum CK activity, which was increased in rat snakes.

Monitoring the estrous cycle of the Asian elephant (Elephas maximus), using urinary estrogens.

The estrous cycle of the Asian elephant (Elephas maximus) was monitored by analysis of urinary estrogens. Daily morning urine samples were analyzed for estrone (E1), estradiol (E2), and total immunoreactive estrogen (ET). The ET values were shown to correlate poorly with E1 and E2 values and failed to reveal any patterns of reproductive cycling. Daily E1 and E2 values, indexed by creatinine concentrations, demonstrated cyclic profiles in those samples of sufficient concentration. The technique offered a simple, noninvasive method of documenting ovarian function in the elephant.

Enzyme-linked immunosorbent assay for the detection of antibodies to the alcelaphine herpesvirus of malignant catarrhal fever in exotic ruminants.

An ELISA for antibodies to the alcelaphine herpesvirus-1 of malignant catarrhal fever was developed. Of sera that represented 42 exotic ruminant species, 216 were evaluated by the ELISA and a virus-neutralization test. A significant correlation (r = 0.564, P less than 0.001, n = 216) between the ELISA and virus-neutralization test results was found. Of the sera having positive test results by virus neutralization, 86.1% also had positive results by the ELISA, and of the sera having negative test results by virus neutralization, 83.9% also had negative results by the ELISA. The presence of antibody, as measured by the ELISA, correlated with clinical signs of malignant catarrhal fever and the isolation of herpesvirus.

Characteristics of the herpesvirus of malignant catarrhal fever isolated from captive wildebeest calves.

A herpesvirus was isolated from buffy coat cells from a newborn wildebeest (Connochaetes gnou) and from tissues of a 12-day-old wildebeest during the 1982 calving season of a captive, inbred herd maintained in a zoologic collection. Both wildebeests were clinically healthy, and there was no herd record that malignant catarrhal fever (MCF) existed. Each viral isolate produced cytopathologic changes in bovine kidney cell cultures (intranuclear inclusions and massive syncytia). The viral-infected cell cultures contained antigens of MCF virus detected by immunofluorescence. The morphology of each viral isolate as determined by electron microscopy was that of a herpesvirus. Suspensions of 4 to 5 ml of disrupted cell culture material which contained virus from each wildebeest were inoculated (IV) into white-tailed deer (Odocoileus virginianus). Each deer became clinically ill within 28 days. Both deer had mucoid catarrh and a febrile response (40.5 to 41 C). Each also seroconverted to MCF virus. The histopathologic change in the tissues from the 2 inoculated deer was vasculitis. At 16 to 17 days after the deer were inoculated, a syncytial-forming virus was isolated from each deer from buffy coat cells fused with polyethylene glycol (1000) to bovine fetal kidney cells. The virus was identified as MCF virus by immunofluorescence and production of antibody to MCF virus. The presence of virus in the inbred wildebeest herd established this species as a reservoir or latent carrier of African MCF virus at the zoologic park.

Immobilization of black bears (Ursus americanus) with orally administered carfentanil citrate.

Ten black bears (Ursus americanus) were immobilized with orally administered carfentanil citrate. The total carfentanil dose was mixed with 5 to 20 ml honey and given incrementally to captive bears. The bears ranged in weight from 80 (estimated) to 233 kg. Total carfentanil doses ranged from 0.7 to 3.0 mg, resulting in dosages of 6.8 to 18.8 micrograms carfentanil/kg. Mean (+/- SD) times from estimated 80% mixture consumption to sternal recumbency, and first safe human contact were 7.7 +/- 2.3 min and 19.7 +/- 5.6 min, respectively. Undesired side effects of immobilization were muscle rigidity, bradypnea, and oxygen desaturation. All bears received diazepam to alleviate muscle rigidity and were insufflated with oxygen during immobilization. Nine immobilizations were considered satisfactory or good. The bear receiving 6.8 micrograms carfentanil/kg, the lowest dosage used, was very excited during induction and required intravenous (IV) ketamine to permit safe examination. Immobilization was reversed with 100 mg naltrexone/mg carfentanil administered (75% subcutaneous, 25% IV). Bears recovered to full mobility in 6.3 +/- 1.9 min. Five bears vomited post-recovery but no episodes of renarcotization were observed.

Antibody responses of red wolves to canine distemper virus and canine parvovirus vaccination.

Twenty captive red wolves (Canis rufus), including 16 intended for release into Great Smoky Mountains National Park, Cades Cove, Tennessee (USA), and four housed at Knoxville Zoological Gardens, Inc., Knoxville, Tennessee, were evaluated for immunologic response to vaccination between June 1994 and April 1995. Wolves were vaccinated with modified-live (MLV) canine distemper virus (CDV) and canine parvovirus type-2 (CPV2). Sera were collected, and immunofluorescent staining was performed for determination of immunoglobulin titers (CDV IgM, CDV IgG, and CPV2 IgG). A capture enzyme-linked immunosorbent assay was performed for validation purposes, to confirm the reactivity of our standard diagnostic reagents with red wolf serum. All wolves produced a measurable antibody response to CDV and CPV2 vaccination. Titers against CDV and CPV2 varied widely among individual wolves, but between-litter differences in mean titers were not significant. No consistent response between the degree of response to CDV versus CPV2 vaccination was observed in individual wolves. No differences were seen between IgG responses of pups vaccinated with univalent vaccines given concurrently or during alternating weeks. Pups had an IgG response to CDV and CPV2 vaccination as early as 9 wk of age. Mean post-vaccination IgG titers against CDV were at or above the level normally measured in vaccinated domestic dogs. Mean post-vaccination IgG titers against CPV2 were below the level normally measured in domestic dogs. Adult previously-vaccinated wolves had measurable CDV and CPV2 IgG titers more than 1 yr after vaccination, but did not have significant IgG titer increases after revaccination. We conclude that red wolves are capable of producing an antibody response after vaccination with commercial canine products but that their response to CPV2 vaccination was minimal. This response can be assayed using tests developed for domestic dogs.

Sedative and physiologic effects of orally administered alpha 2-adrenoceptor agonists and ketamine in cats.

OBJECTIVE: To compare efficacy of 3 regimens of orally administered sedatives and determine physiologic effects of 1 of these regimens in healthy cats. DESIGN: Prospective randomized study. ANIMALS: 34 cats. PROCEDURE: Cats were assigned to 1 of 3 groups that were treated by oral administration of detomidine and ketamine, xylazine and ketamine, or medetomidine and ketamine. Cats were monitored for degree of sedation at 5-minute intervals for 60 minutes. Physiologic effects in cats treated with detomidine and ketamine were measured at 5-minute intervals for 30 minutes and compared with effects in cats treated i.m. with detomidine and ketamine or xylazine and ketamine. RESULTS: All cats treated orally with detomidine and ketamine became laterally recumbent; sedation was more variable in the other 2 groups treated orally. Vomiting and excessive salivation were the only adverse effects. Bradycardia (heart rate < 145 beats/min) was detected at each evaluation time in cats treated orally with detomidine and ketamine and in all cats treated i.m. Minimal differences among groups were detected for heart and respiratory rates, rectal temperature, and hemoglobin oxygen saturation. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of detomidine and ketamine is an effective method of sedating healthy cats and induces minimal physiologic effects that are similar to those resulting from i.m. administration of sedatives.

Comparison of five regimens for oral administration of medication to induce sedation in dogs prior to euthanasia.

OBJECTIVE: To compare regimens for oral administration of medication to induce sedation in dogs prior to euthanasia. DESIGN: Prospective randomized clinical study. ANIMALS: 37 dogs. PROCEDURE: Groups and medications were as follows: group 1, acepromazine (n = 8); group 2, tiletamine-zolazepam (8); group 3, tiletamine-zolazepam and acepromazine (8); group 4, tiletamine-zolazepam and butorphanol (6); and group 5, pentobarbital sodium (7). Capsules or tablets were placed in each dog's food. Sedation was scored at 3-minute intervals after consumption of medication for at least 60 minutes. Dogs with signs of persistent or progressive sedation were observed for 90 minutes. RESULTS: Only 2 dogs in group 1 became slightly ataxic. All group-2 dogs were slightly ataxic, and 4 of 8 became laterally recumbent (mean time to lateral recumbency, 62 minutes). Seven of 8 group-3 dogs became sternally recumbent, and 6 of these dogs became laterally recumbent (mean, 48.6 minutes). Four of 6 group-4 dogs were slightly or moderately ataxic, and 1 of these dogs became laterally recumbent (mean, 48 minutes). One dog in group 5 was not affected by the medication, but all other group-5 dogs became laterally recumbent (mean, 59 minutes). CLINICAL IMPLICATIONS: Of the medications evaluated, tiletamine-zolazepam and acepromazine at dosages of approximately 20 mg/kg (9.1 mg/lb) and 2 mg/kg (0.91 mg/lb), respectively, or pentobarbital sodium alone (63.2 +/- 5.1 mg/kg [28.7 +/- 2.3 mg/lb]) most consistently induced profound sedation and lateral recumbency after oral administration to dogs.

Comparison of four regimens for intraoral administration of medication to induce sedation in cats prior to euthanasia.

OBJECTIVE: To compare 4 regimens for intraoral administration of medication to induce sedation in cats prior to euthanasia. DESIGN: Prospective randomized clinical study. ANIMALS: 36 cats. PROCEDURE: Cats were assigned to 4 groups (9 cats/group). Cats in each group were given the following medications: group 1, detomidine (0.5 mg/kg [0.23 mg/lb] of body weight); group 2, ketamine hydrochloride (5 mg/kg [2.3 mg/lb]); group 3, detomidine (0.5 mg/kg) and ketamine (5 mg/kg); and group 4, detomidine (0.5 mg/kg) and ketamine (10 mg/kg [4.5 mg/lb]). All medications were administered by squirting the drug or drug combination into the mouth of a cat, using a syringe or, for intractable cats, a remote delivery device. Cats were evaluated for degree of sedation at 3-minute intervals for 60 minutes. RESULTS: Of the 9 cats in group 1, 7 assumed lateral recumbency. Mean (+/- SD) interval from administration of medication to lateral recumbency was 15 +/- 3 minutes. For group-2 cats, 1 cat achieved sternal recumbency (sternally recumbent and unable to stand), whereas the remaining 8 cats achieved mild to moderate degrees of sedation. For group 3, 6 of 9 cats assumed lateral recumbency (mean, 16.5 +/- 3.7 minutes). For group 4, all 9 cats assumed lateral recumbency (mean, 17 +/- 8 minutes). CLINICAL IMPLICATIONS: Analysis of results of this study indicated that a combination of detomidine (0.5 mg/kg) and ketamine (10 mg/kg) administered intraorally provide an effective and reliable method for sedating cats.

Detection and control of rotavirus infections in zoo animals.

Fecal specimens from 15 exotic animal species, with and without diarrhea, were examined for the presence of rotavirus, bacterial enteropathogens, and intestinal parasites. A commercial enzyme-linked immunosorbent assay was used to detect antigens of rotavirus. Rotavirus was detected in the feces of 20 (57%) of 35 of the animals, which included addax (Addax nasomaculatus), nyala (Tragelaphus angasi), saiga (Saiga tatarica), white-tailed gnu (Connochaetus gnou), greater kudu (Tragelaphus strepsiceros), sitatunga (Tragelaphus spekei), Grant's gazelle (Gazella granti roosevelti), sable antelope (Hippotragus niger niger), kob (Kobus kob leucotis), pygmy marmoset (Callithrix pygmaea), bush dog (Speothos venaticus), grizzly bear (Ursus arctos horribilis), and red kangaroo (Megaleia rufa). Bacterial pathogens were found in 8 animals, 5 of which had concurrent rotavirus infections. Most (60%) of the animals with rotavirus infection were less than 2 weeks old; however, rotavirus also was detected in feces from adult animals. Although most of the cases of rotavirus infection were detected in nursery-reared animals, exhibit-reared animals also were infected with rotavirus.

Degenerative spinal disease in large felids.

Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

Fungal dermatitis in captive pinnipeds.

Fungal dermatitis was diagnosed in two captive gray seals (Halichoerus grypus) and four harbor seals (Phoca vitulina) between 1992 and 1994. Trichophyton mentagrophytes, Malassezia spp., and Yarrowia (Candida) lipolytica were isolated. Erythematous, thickened, alopecic skin lesions were present on the face and on the flippers, particularly around the nail bed. The two most important environmental factors associated with development of fungal dermatitis appeared to be excessive chlorination of pool water and warm water temperature.

Oral induction of anesthesia with droperidol and transmucosal carfentanil citrate in chimpanzees (Pan troglodytes).

Five chimpanzees (Pan troglodytes) initially received oral droperidol sedation (1.25 mg for a juvenile chimpanzee, body wt = 18.5 kg, and 2.5 mg for adults, body wt >20 kg, range: 18.5-71 kg) followed by transmucosal carfentanil administration at 2.0 microg/kg. This preinduction regimen was developed to produce heavy sedation or even light anesthesia in order to eliminate the need for or at least minimize the stress of darting with tiletamine/zolazepam at 3 mg/kg i.m. This study was designed to assess the safety and efficacy of transmucosal carfentanil. Once each animal was unresponsive to external stimuli, or at approximately 25 min (range 24-34 min) after carfentanil administration, naltrexone and tiletamine/zolazepam (N/T/Z) were combined into one intramuscular injection for anesthetic induction. Naltrexone was administered at 100 times the carfentanil dose in milligrams. For comparison, two chimpanzees received only droperidol, 2.5 mg p.o., followed by tiletamine/zolazepam, 3 mg/kg i.m. The preinduction period for all animals receiving carfentanil was characterized as smooth, with chimpanzees becoming gradually less active and less responsive to external stimuli. Two animals became very heavily sedated at 24 and 35 min, respectively, and were hand injected with N/T/Z. The other three chimpanzees became sternally recumbent but retained some response to stimuli, and N/T/Z was administered by remote injection with minimal response. Rectal body temperatures, pulse and respiratory rates, arterial oxygen hemoglobin saturation, and arterial blood gases were measured at initial contact (t = 0 min) and at 10-min intervals thereafter. Respiratory depression was present in all chimpanzees, regardless of protocol. Mean hemoglobin saturation was 91% for both groups. Mean partial pressure of oxygen, arterial values for carfentanil-treated and control animals were 64.4 +/- 7.6 and 63.5 +/- 6.0 at t = 0, respectively. Only the partial pressure of carbon dioxide, arterial (Paco2) and pH showed significant differences between treated and control animals. Mean Paco2 was greater and mean pH lower for the carfentanil-treated group compared with the controls at t = 0 (58.9 +/- 3.7 and 50.3 +/- 3.1 for Paco2 and 7.33 +/- 0.02 and 7.40 +/- 0.30 for pH, respectively). The results of this study suggest that oral droperidol followed by transmucosal carfentanil can be used effectively as a premedication regimen to produce profound sedation, which limits the stress of darting during parenteral anesthetic induction with tiletamine/zolazepam in chimpanzees. The main side effect of respiratory depression appears to be adequately managed by reversing the carfentanil at the time of induction.