Pathogenicity of Pasteurella multocida A:3 in Flemish giant and New Zealand white rabbits.

Pasteurella multocida A:3 was isolated during an outbreak of pasteurellosis in Flemish Giant (FG) rabbits. Since New Zealand White (NZW) rabbits housed in the same room were not as severely affected as FG rabbits, experimental inoculation was undertaken to determine if FG rabbits were more susceptible than NZW rabbits to pasteurellosis induced by this isolate. Rabbits of each breed were inoculated with P. multocida A:3 and observed for 3 weeks. Four of 5 FG rabbits developed severe clinical disease on days 6, 9, 12 and 14 after inoculation; whereas, the one affected NZW rabbit became ill 14 days after inoculation. All rabbits with clinical disease developed fibrinosuppurative pleuritis, pyothorax and pneumonia which was more severe in FG than NZW rabbits. At necropsy, P. multocida A:3 was isolated from multiple sites of the diseased rabbits. No significant difference (P = 0.099) in the prevalence of lesions between the two breeds was found; however, the score of pneumonia and pleuritis was 3 times greater in FG rabbits than NZW rabbits.     

Effects of a new injectable short-term release deslorelin in foal-heat mares

Mares treated with subcutaneous deslorelin implants on the first postpartum estrus early in the breeding season had significant reductions in the number of large follicles at early pregnancy examinations and delayed return to estrus (in mares that failed to become pregnant); these adverse effects were attributed to a prolonged release of the drug from the implant. In 2003, an injectable short-term release (<24 h) deslorelin product became available. The objective of this study was to determine if this product would hasten ovulation in early foaling first postpartum estrus mares without reducing the number of large follicles at early pregnancy examination (14-15 days postovulation). Beginning 5-6 days postpartum, first postpartum estrus (foal-heat) mares were teased daily and examined thrice weekly (Tuesday, Thursday and Saturday) by transrectal ultrasonography. Mares in estrus with a follicle > or = 34 mm diameter on Tuesdays or Thursdays were alternately assigned to: Treatment 1, n = 17; 1.5 mg injectable short-term release deslorelin, or Treatment 2, n = 16; Control (no treatment). The schedule allowed accurate determination of the number of mares ovulating within 2 days of treatment (i.e., ovulations detected on Thursday or Saturday). Mares were mated on the day of treatment and at 2-day intervals until either ovulation was confirmed or until behavioral estrus ceased. Transrectal ultrasonography was done 14-15 days after ovulation to assess ovarian follicles and pregnancy status. Fewer covers were required and more mares ovulated within 2 days of treatment in deslorelin-treated versus Control mares (P < 0.01). Pregnancy rates were normal (69%) in deslorelin-treated mares. The number of large follicles 14-15 days after ovulation did not differ between deslorelin-treated and Control mares (P > 0.10), suggesting follicular suppression did not occur with this formulation of deslorelin.     

Serologic methods for detection of Pasteurella multocida infections in nasal culture negative rabbits

An agar gel-diffusion test (AGDT) and an enzyme-linked immunosorbent assay (ELISA) were utilized to detect serum antibodies against Pasteurella multocida in naturally infected rabbits derived originally from a Pasteurella-free colony. The antigen used in both assays was purified from a serotype 3 (P-1059) strain of P. multocida. Among 47 serum samples tested 15 (32%) were seropositive; 12 (26%) of which were both AGDT and ELISA-positive, while 3 (6%) were ELISA-positive only. All rabbits examined were normal clinically and negative to repeated nasal cultures, but subsequent cultures at necropsy demonstrated the presence of P. multocida in 11 of the AGDT-positive rabbits and in 14 of the ELISA-positive rabbits. The organism was isolated most frequently from the naso-oropharynx and the tympanic bullae. Serotyping of isolates recovered from the nasopharynx were determined to be serotype 3 or 3,12. Ten seronegative rabbits also were necropsied and none were found harboring P. multocida. These preliminary data indicate that the application of an enzyme-linked immunosorbent assay may prove efficacious in identifying apparently healthy, consistently nasal culture-negative rabbits as subclinical carriers of P. multocida.     

Evaluation of a new progestin (Sa 45.249) in cattle

Daily oral administration of the progestin Sa 45.249 to 80 cycling heifers, at doses ranging from 6 to 14 mg/day and over varying treatment periods (from 8 to 16 days) resulted in all animals in complete estrus inhibition. Irrespective of the dose and the treatment period used, heat and ovulations — as judged by the corpora lutea which became palpable on day 15 of this cycle — occurred between day 2 and 9 after cessation of treatment in 73 of 80 heifers (91%). Neither the daily dose nor the duration of treatment had any discernible effect on the occurrence of heat.This pattern was confirmed in a pilot field trial. From artificial insemination at the first and second heat after treatment, 16 of 21 treated heifers (76%) and 45 of 55 cows (80%) were pregnant. There was no difference in cyclic plasma progesterone levels between heifers treated for 14 days with 10 mg Sa 45.249 and untreated controls, when treatment commenced either on day 5 or 14 of the cycle, with the exception of the delay in the post-ovulatory rise in the latter treatment.     

Effects of sulfadiazine and amprolium on Neospora caninum (Protozoa: Apicomplexa) infections in mice

An immunosuppressed mouse model was used to determine the effects of amprolium and sulfadiazine on experimental Neospora caninum infections. Both drugs were given in the drinking water. Neither drug was effective in treating infections when given 7 days after inoculation of tachyzoites, when clinical signs of disease had developed. Amprolium did not prevent deaths or development of clinical signs when given in the drinking water at 1 mg/ml or 5 mg/ml 3 days after inoculation of tachyzoites. Sulfadiazine in drinking water was not effective when given at 0.5 mg/ml but was effective in preventing deaths and clinical disease when given at 1 mg/ml 3 days after inoculation with tachyzoites. Most mice (6 of 10) treated for 3 days with 1 mg/ml sulfadiazine in drinking water developed encephalitis after drug treatment was stopped. Treatment for 14 days with 1 mg/ml sulfadiazine in drinking water was needed to protect 90% of inoculated mice.     

Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir.

The efficacy of the new nucleoside analogue acyclovir against B virus (Herpesvirus simiae) was investigated in rabbits and Vero cells infected with 2-136 and 0.3-1.0 TCD50 of the virus respectively. In the Vero cells 1 mg of acyclovir/1 reduced the yield of virus by 90%, which was slightly less than the effect on herpes simplex virus. Results in the rabbits varied with the interval between doses, duration of treatment, and delay before starting treatment. Acyclovir controlled an otherwise lethal infection when given not less than eight-hourly for 14 days. Withdrawing treatment after 9-10 days resulted in late-onset fatal disease in some rabbits. Treatment begun within 24 hours after infection gave complete protection, and rabbits first treated up to five days after infection showed a significant reduction in mortality (p less than 0.001). The plasma half life of acyclovir is twice as long in man as in rabbits and progression of the disease is much slower. Hence acyclovir may be useful for post-exposure prophylaxis against B virus infection in man and possibly also for treatment of the disease.     

Field trial of a live streptomycin dependent Pasteurella multocida serotype A:12 vaccine in rabbits

A live, streptomycin dependent, Pasteurella multocida (SDPM) serotype A:12 vaccine was evaluated for preventing pasteurellosis in two commercial rabbitries. Rabbits were inoculated intranasally at 5 weeks old with either 0.25 ml of vaccine containing 10(8) colony forming units/ml or 0.25 ml of diluent (control). A proportion of rabbits received a second intranasal inoculation 1 month later. Partial protection against P. multocida infection was observed 1 and 2 months after inoculation in rabbits given only one dose of vaccine. The incidence of clinical signs of pasteurellosis was similar in vaccinated and nonvaccinated market-age rabbits inoculated 4 to 6 weeks previously. In does maintained in the breeding colony, P. multocida infection and upper respiratory disease occurred more frequently in vaccinated than nonvaccinated rabbits. Humoral antibody responses (IgA, IgM, IgG) followed longitudinally were similar in vaccinated and nonvaccinated does. Hence, the SDPM vaccine was not efficacious in controlling P. multocida infection at these two rabbitries.     

Survival of toxigenic Pasteurella multocida in aerosols and aqueous liquids.

The survival of toxigenic Pasteurella multocida in air and liquids was studied to identify possible risk factors in the etiology of atrophic rhinitis. In aerosols, at low relative humidity (28%), the viability of toxigenic P. multocida 5 min after aerosolization was at least 22% of its initial value. Viability at low relative humidity declined to 8% after 45 min. Viability at high relative humidity (79%) was 69% after 5 min and declined to 2% after 45 min. Survival of toxigenic P. multocida in liquids depended on storage and constituents in the liquid. Toxigenic P. multocida became nonculturable 1 to 14 days after inoculation in water and artificial seawater, depending on the storage temperature. Toxigenic P. multocida stored at 37 degrees C could be detected for up to 6 days in pig slurry and more than 36 days in Bacto Tryptose broth and nasal lavages. However, in Bacto Tryptose broth and nasal lavages stored at 4 degrees C, P. multocida was detected for up to 14 days whereas at 15 and 37 degrees C it was detected for more than 49 days. These results suggest that aerosols and fomites can play a role in the transmission of atrophic rhinitis.     

An enzyme-linked immunosorbent assay to detect serum IgG to Pasteurella multocida in naturally and experimentally infected rabbits

An enzyme-linked immunosorbent assay (ELISA) was evaluated for efficacy in detecting serum IgG against Pasteurella multocida in both naturally and experimentally infected rabbits. Blood samples and nasal cultures were taken concurrently from 58 rabbits from four conventional rabbitries. Nine rabbits from a pasteurella-free colony served as negative controls. Fifty-six rabbits were ELISA positive. Of these, 46 were P. multocida culture positive, 10 were culture negative. Two rabbits were ELISA negative, culture negative. There were no ELISA negative, culture positive animals. Serotyping by the gel diffusion precipitin test demonstrated that of the 44 typed P. multocida isolates, 57% were serotype 4, 27% were serotype 12 and 16% were serotype 3. In rabbits experimentally infected intranasally with P. multocida, serum IgG against P. multocida began to rise 21 to 33 days after infection and remained elevated until the animals were euthanized 90 days post infection. Two enzyme-linked immunosorbent assays were compared which used potassium thiocyanate extracts of different serotypes of P. multocida as antigen. The results obtained were similar, suggesting the presence of antigens common to both serotypes.     

Survival of toxigenic Pasteurella multocida in aerosols and aqueous liquids.

The survival of toxigenic Pasteurella multocida in air and liquids was studied to identify possible risk factors in the etiology of atrophic rhinitis. In aerosols, at low relative humidity (28%), the viability of toxigenic P. multocida 5 min after aerosolization was at least 22% of its initial value. Viability at low relative humidity declined to 8% after 45 min. Viability at high relative humidity (79%) was 69% after 5 min and declined to 2% after 45 min. Survival of toxigenic P. multocida in liquids depended on storage and constituents in the liquid. Toxigenic P. multocida became nonculturable 1 to 14 days after inoculation in water and artificial seawater, depending on the storage temperature. Toxigenic P. multocida stored at 37 degrees C could be detected for up to 6 days in pig slurry and more than 36 days in Bacto Tryptose broth and nasal lavages. However, in Bacto Tryptose broth and nasal lavages stored at 4 degrees C, P. multocida was detected for up to 14 days whereas at 15 and 37 degrees C it was detected for more than 49 days. These results suggest that aerosols and fomites can play a role in the transmission of atrophic rhinitis.     

Safety and efficacy of a streptomycin dependent live Pasteurella multocida vaccine in rabbits

The safety of and protection provided by a streptomycin dependent live Pasteurella multocida (serotype 12:A) vaccine was evaluated in New Zealand white rabbits. The vaccine strain was isolated from two of twelve rabbits 24 hours after intranasal administration. Streptomycin independent P. multocida isolates were not recovered for 4 weeks after vaccination, indicating a lack of reversion to the wild type. Thirty days after a single intranasal administration of vaccine, eight rabbits were challenged with either P. multocida serotype 3:A or serotype 12:A. Eight non-vaccinated rabbits were challenged in the same manner. Vaccinated rabbits challenged with serotype 12:A had nasal infections for only 2 weeks following challenge. Vaccinated rabbits challenged with serotype 3:A developed chronic nasal infections but were protected from severe disease. Immunoglobulin A or G antibodies against P. multocida were not detected after vaccination in nasal lavages or sera using an enzyme-linked immunosorbent assay. However, both antibodies increased following challenge with either serotype 3:A or serotype 12:A. These studies indicated that the streptomycin dependent pasteurella strain colonized rabbits briefly and was genetically stable in vivo. The results in challenged rabbits suggest that the vaccine provided protection against chronic infection by a homologous pasteurella serotype and protection against severe disease by a heterologous pasteurella serotype.     

Immunization of rabbits against Pasteurella multocida using a commercial swine vaccine

Elaboration of heat-labile toxin (PMT) is an important virulence factor in some isolates of Pasteurella multocida from rabbits. Previously, we reported that immunization with inactivated PMT (IPMT) stimulated protective immunity to challenges from PMT. To test the hypothesis that immunization with a commercial swine vaccine containing IPMT stimulates similar protective immunity, groups of five rabbits were inoculated twice intramuscularly (i.m.), 10 days apart, with 0.5 ml of sterile saline or a commercial swine P. multocida bacterin-toxoid (BT). In addition, a group was inoculated intranasally with 5 microg of IPMT. Serum and nasal lavage samples were taken on days 0, 7, 14 and 21 after initial immunization and assayed by ELISA for anti-PMT antibody. Serum IgG and nasal lavage IgA were detectable by day 14 in BT and IPMT-immunized rabbits, but not in the saline controls. Groups of similarly inoculated rabbits were then challenged intranasally with 28 microg of PMT 21 days after initial immunization, and necropsied 7 days later, along with control challenged and non-challenged rabbits. Histological lesion severity was graded on a numerical scale. Non-immunized and saline, challenged controls developed more severe pneumonia, pleuritis, nasal turbinate atrophy and testicular atrophy than IPMT and BT-immunized rabbits. The results confirm the hypothesis that immunization with a commercial swine P. multocida BT confers protective immunity in rabbits against challenges from PMT.     

Comparison of the Safety and Pharmacokinetics of ST-246? after IV Infusion or Oral Administration in Mice,Rabbits and Monkeys

Background

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation.

Methodology/Principal Findings

The pharmacokinetics of ST-246 after IV infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute IV infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short IV infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and IV infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C_max plasma concentrations. These effects were eliminated using slower IV infusions.

Conclusions/Significance

Pharmacokinetic profiles after IV infusion compared to those observed after oral administration demonstrated the necessity of longer IV infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C_max associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion.     

Moxidectin evaluation against Solenoptes capillatus (Anoplura: Linognathidae), Bovicola bovis (Mallophaga: trichodectidae), and Musca autumnalis (Diptera: Muscidae) on cattle.

Slow release formulations of 375, 750, and 1,125 mg (AI) in 50-g boluses and a subcutaneous injectable formulation (0.2 mg AI/kg body wt) of moxidectin (CL301423) were tested for the control of the little blue cattle louse, Solenoptes capillatus (Enderlein), and the cattle biting louse, Bovicola bovis (L). S. capillatus populations were reduced 4 wk after treatment and complete control was observed 6 wk after treatment in groups treated with boluses, B. bovis were first observed at 3 wk and continued to increase throughout the 14-wk test period. These were experimental boluses and future boluses may perform differently. Subcutaneous injections of moxidectin gave complete control of S. capillatus for a 27-d test period. Feces from animals treated with boluses were tested with face fly larvae, Musca autumnalis De Geer, to demonstrate fecal activity of moxidectin. Larval mortality in these groups ranged from 90 to 30% from 2 d to 10 wk after treatment.     

Intravenous tissue plasminogen activator and size of infarct,left ventricular function,and survival in acute myocardial infarction.

STUDY OBJECTIVE--To assess effect of intravenous recombinant tissue type plasminogen activator on size of infarct, left ventricular function, and survival in acute myocardial infarction. DESIGN--Double blind, randomised, placebo controlled prospective trial of patients with acute myocardial infarction within five hours after onset of symptoms. SETTING--Twenty six referral centres participating in European cooperative study for recombinant tissue type plasminogen activator. PATIENTS--Treatment group of 355 patients with acute myocardial infarction allocated to receive intravenous recombinant plasminogen activator. Controls comprised 366 similar patients allocated to receive placebo. INTERVENTION--All patients were given aspirin 250 mg and bolus injection of 5000 IU heparin immediately before start of trial. Patients in treatment group were given 100 mg recombinant tissue plasminogen activator over three hours (10 mg intravenous bolus, 50 mg during one hour, and 40 mg during next two hours) by infusion. Controls were given placebo by same method. Full anticoagulation treatment and aspirin were given to both groups until angiography (10-22 days after admission). beta Blockers were given at discharge. END POINT--Left ventricular function at 10-22 days, enzymatic infarct size, clinical course, and survival to three month follow up. MEASUREMENTS AND MAIN RESULTS--Mortality was reduced by 51% (95% confidence interval -76 to 1) in treated patients at 14 days after start of treatment and by 36% (-63 to 13) at three months. For treatment within three hours after myocardial infarction mortality was reduced by 82% (-95 to -31) at 14 days and by 59% (-83 to -2) at three months. During 14 days in hospital incidence of cardiac complications was lower in treated patients than controls (cardiogenic shock, 2.5% v 6.0%; ventricular fibrillation, 3.4% v 6.3%; and pericarditis, 6.2% v 11.0% respectively), but that of angioplasty or artery bypass, or both was higher (15.8% v 9.6%) during the first three months. Bleeding complications were commoner in treated than untreated patients. Most were minor, but 1.4% of treated patients had intracranial haemorrhage within three days after start of infusion. Enzymatic size of infarct, determined by alpha hydroxybutyrate dehydrogenase concentrations, was less (20%, 2p = 0.0018) in treated patients than in controls. Left ventricular ejection fraction was 2.2% higher (0.3 to 4.0) and end diastolic and end systolic volumes smaller by 6.0 ml (-0.2 to -11.9) and 5.8 ml (-0.9 to -10.6), respectively, in treated patients. CONCLUSION--Recombinant tissue type plasminogen activator with heparin and aspirin reduces size of infarct, preserves left ventricular function, and reduces complications and death from cardiac causes but at increased risk of bleeding complications4+     

Failure of the platelet-activating-factor antagonist WEB 2086 BS for treatment of chronic autoimmune thrombocytopenia

Thirteen patients with chronic autoimmune thrombocytopenia (AITP) were treated for 14 days with daily oral doses of 120 mg of the novel platelet-activating-factor (PAF) antagonist WEB 2086 BS. Clinical bleeding symptoms remained essentially unchanged in 9 patients and became more pronounced in the post-treatment period in 4 patients. In no case was an increase in platelet counts observed. While the PAF antagonist was well tolerated subjectively during treatment, most patients exhibited a prolongation of the sensitive "hemostasis time" (a modified bleeding time test) after treatment, but the Duke bleeding time was not changed. We conclude that the PAF antagonist WEB 2086 BS is ineffective for treatment of chronic AITP and should be used with caution in thrombocytopenic patients.     

Diagnosis and treatment of conjunctivitis in house finches associated with mycoplasmosis in Minnesota

An ongoing outbreak of Mycoplasma gallisepticum-associated conjunctivitis in house finches (Carpodacus mexicanus) that began in 1994 in the eastern United States has been spreading westward. House finches presenting with the clinical signs of M. gallisepticum-associated conjunctivitis were first seen at the Wildlife Rehabilitation Center of Minnesota (Minnesota, USA) in July of 1996, and 42 cases were admitted from 26 December 1996 to 10 August 1997. A nested PCR was designed for sensitive and specific detection of the presence of the organism. Twelve birds were treated with oral enrofloxacin (15 mg/kg, twice daily for 21 days) and ophthalmic gentamicin (twice daily for 21 days). All treated birds showed resolution of clinical signs. Following treatment, finches were held for up to 6 mo and tested for the presence of M. gallisepticum by culture and nested polymerase chain reaction (PCR). Eight of twelve finches (67%) were positive for M. gallisepticum by nested-PCR and four (33%) were positive by culture. The results suggest that oral enrofloxacin and opthalmic gentamicin are not an effective treatment for the eradication of M. gallisepticum in house finches. Further, the results show that nested PCR is an effective method for detection of M. gallisepticum in house finches and was more sensitive than culture.     

Dose-dependent hyperlipidemia in rabbits following administration of poloxamer 407 gel

Poloxamer 407 (P-407) is a tri-block polymer that exhibits concentration-dependent reverse thermal gelation, a characteristic potentially useful for developing sustained release injectable drugs. While some reports suggest that P-407 is 'non-toxic', rodent studies demonstrate that P-407 induces hyperlipidemia, an action that makes this polymer a questionable drug delivery vehicle. Unfortunately, the majority of earlier studies employed supra-physiologic doses of P-407. The present study examined if lower, clinically useful, doses of gel-forming concentrations of P-407 induced hyperlipidemia in rabbits. Male and female rabbits were injected with 5.5 mg/kg (0.025 mL/kg), 27.5 mg/kg (0.125 mL/kg), or 137.5 mg/kg (0.625 mL/kg) of 22% P-407 and the actions of this polymer on blood chemistry were assessed at 6 h, 1 d, 2 d, 7 d, and 14 d following injection. Control rabbits received no injection. The highest dose of P-407 (137.5 mg/kg) significantly increased serum triglycerides and cholesterol in both male and female rabbits with the maximum increase observed at 2 d after injection. Male rabbits were more sensitive to P-407 than females following injection of 137.5 mg/kg P-407. The lower doses of P-407 did not alter serum triglycerides or cholesterol. In all groups, serum triglycerides and cholesterol were at baseline levels by 14 d. P-407 did not affect other blood chemistry parameters. Although P-407 induces a dose-dependent hyperlipidemia in rabbits, low doses of this polymer may be used in controlled release drug delivery applications without the untoward hyperlipidemic effect.     

Adjunctive pharmacologic treatment for elective stenting of the extracranial carotid arteries

Endovascular stenting of the extracranial carotid arteries is a viable treatment option to carotid endarterectomy in selected patients. Patients undergoing this procedure must be treated with aspirin 325 mg at least 24 hours prior to the procedure and clopidogrel 75 mg oral, three to five days prior to the procedure (or 300 mg at least six hours prior to stenting). During the intervention, heparin is given to maintain an activated clotting time of at least 300 seconds. Although there are theoretical advantages on the use of a platelet IIb/IIIa inhibitor, their routine use during elective carotid stenting is not recommended until their clinical benefits have been clearly demonstrated in this patient population. Hemodynamic instability during balloon inflation and stent deployment should be treated with intravenous fluids, atropine, and an alpha agonist such as neosynephrine. All the oral antihypertensive must be discontinued after the procedure and if there is persistence of hypotension making discontinuation of neosynephrine difficult, an oral alpha agonist such as midodrine (2.5 to 5 mg two to three times daily) is helpful. In the majority of patients this medication can be tapered off three to five days following stenting.     

The effects of prolonged ketamine-xylazine intravenous infusion on arterial blood pH, blood gases, mean arterial blood pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit

The prolonged and safe maintenance of general anesthesia in rabbits with commonly used injectable agents is difficult. Protracted, stable anesthesia with short recovery time has been described in humans using continuous intravenous infusion of ketamine with or without sedatives, muscle relaxants and paralytics. This study evaluated the anesthetic plane achieved and respiratory and cardiovascular effects produced with a ketamine-xylazine intravenous infusion in New Zealand White rabbits. Ten female rabbits were anesthetized with intramuscularly administered ketamine hydrochloride (35 mg/kg) and xylazine hydrochloride (5 mg/kg) after the preanesthetic, baseline measurements of arterial blood pO2, pCO2 and pH and heart and respiratory rates were recorded. The above parameters as well as mean arterial blood pressure, righting, palpebral, pedal, and jaw reflexes were monitored ten minutes after the intramuscularly administered dosage and throughout 4 hours of infusion. Results showed moderate hypotension (21.2% deviation from normal, p less than 0.008) and profound hypoxemia (45% deviation from baseline, p less than 0.001) 10 minutes after the intramuscularly administered induction dosage. Then, the 4 hour infusion of ketamine (1 mg/minute) and xylazine (0.1 mg/minute) was started. Hypotension progressed (49.1% deviation from normal, p less than 0.008), but hypoxemia and hypercarbemia gradually improved with no resultant change (p greater than 0.1) in arterial pH. There was no significant change (p greater than 0.1) in respiratory rate but varying qualities of respiration were observed. Both mean arterial pO2 and pCO2 values returned to baseline within 20 minutes after completion of infusion. Heart rate and rectal temperature remained stable during the trial. The righting reflex was abolished in all rabbits throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)