Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease.

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.     

Clinical, clinicopathologic, and parasitologic observations of trypanosomiasis in dogs infected with North American Trypanosoma cruzi isolates

Nineteen purebred Beagles of various ages (4, 5, 13, and 47 weeks) were inoculated with North American Trypanosoma cruzi isolates obtained from an opossum (Tc-O), an armadillo (Tc-A), or a dog (Tc-D). Dogs were grouped on the basis of clinical outcome of infection. During the acute stage of disease, dogs of group 1 (n = 7 inoculated with Tc-O or Tc-A) died or were euthanatized because of the severity of disease. Dogs of group 2 (n = 5 inoculated with Tc-O or Tc-A) developed acute disease, but survived to develop chronic disease. Dogs of group 3 (n = 7 Tc-D-inoculated dogs) developed neither acute nor chronic disease. Dogs of group 4 (n = 4--2 dogs 13 weeks old and 2 dogs 47 weeks old) served as noninoculated controls. Clinical signs associated with severe acute myocarditis developed in dogs of groups 1 and 2 between postinoculation day (PID) 15 and 28. Generalized lymphadenopathy and lymphocytosis were observed in all dogs of groups 1, 2, and 3 between PID 14 and 17. Serum alanine transaminase and aspartate transaminase activities and urea nitrogen concentration were high, and glucose concentration was low prior to death of dogs in group 1. Serum activities of isoenzymes of creatine kinase were significantly (P less than 0.05) high in only 1 dog (group 1), whereas serum lactate dehydrogenase isoenzyme activities were not significantly high in any dog.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clearance of indocyanine green in dogs with partial hepatectomy, hepatic duct ligation, and passive hepatic congestion

Clearance of 5 submaximal doses of indocyanine green (ICG) was measured in 5 dogs to determine the maximal removal rate (0.188 mg/kg of body weight/min) and Michaelis constant (Km, 1.25 mg/kg). From these results, 5 mg of ICG/kg of body weight was chosen on the basis of the recommendation that the dose should be at least 4 X Km to achieve sensitivity as a measure of hepatic function and independence from hepatic blood flow. Clearances of low (0.5 mg/kg) and high (5 mg/kg) doses of ICG were measured in 35 healthy dogs to determine reference values. Fractional disappearance was 15.1 +/- 10%/min for the low dose and 3.9 +/- 1%/min for the high dose; plasma half-life was 6.3 +/- 3.6 minutes and 19 +/- 4.8 minutes, respectively. The sensitivity of 2 doses of ICG was evaluated in dogs with 20% and 40% hepatectomy, nonhyperbilirubinemic obstructive cholestasis, or hepatic congestion; sham-operated dogs served as controls. Fractional disappearance and plasma half-life of ICG in the 40% hepatectomy and hepatic congestion groups were significantly different (P less than 0.05) from those in controls using both ICG doses, indicating that both doses were affected by hepatic perfusion, as well as hepatic mass. The fractional disappearance of the dye in the cholestasis group also differed significantly (P less than 0.05) from that of the controls at the high dose. Plasma clearance of both doses by dogs with 20% hepatectomy was not significantly different from that of controls.     

Effects of small intestinal ischemia and reperfusion on expression of tumor necrosis factor-alpha and interleukin-6 messenger RNAs in the jejunum, liver, and lungs of dogs

OBJECTIVE: To determine the effects of intestinal ischemia and reperfusion on the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs in the jejunum, liver, and lungs of dogs. ANIMALS: 8 healthy adult Beagles. PROCEDURES: In each dog, the cranial mesenteric artery was occluded for 0 (control group; n=4) or 60 (I-R group; 4) minutes, followed by reperfusion for 480 minutes; serum TNF-alpha and IL-6 activities and expression levels of TNF-alpha and IL-6 mRNAs in jejunal, hepatic, and lung tissues were measured before and at the end of the ischemic period and at intervals during reperfusion. For each variable, values were compared between the control and I-R groups at each time point. RESULTS: Compared with the control group, serum IL-6 activity increased significantly after 180 minutes of reperfusion in the I-R group; also, jejunal TNF-alpha mRNA expression increased significantly after 60 (peak) and 180 minutes of reperfusion. In the I-R group, expressions of IL-6 mRNA in the liver and TNF-alpha and IL-6 mRNAs in the lungs increased significantly at 480 minutes of reperfusion, compared with the control group. Serum TNF-alpha activity, expression of IL-6 mRNA in the jejunum, and expression of TNF-alpha mRNA in the liver in the control and I-R groups did not differ. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the liver, lungs, and jejunum contributed to the production of TNF-alpha and IL-6 after intestinal ischemia and reperfusion in dogs, suggesting that intestinal ischemia and reperfusion induce a systemic proinflammatory cytokine response in dogs.     

Hepatic effects of halothane, isoflurane or sevoflurane anaesthesia in dogs

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty-one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between 13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre-anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12-14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre-medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.     

The effects of thyroid hormones on the skin of beagle dogs

The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in skin biopsy samples from 3 groups of age- and gender-matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid by administration of 131I; and (3) dogs made hypothyroid and maintained in a euthyroid state by treatment with synthetic thyroxine. After 10 months of observation, there was slower regrowth of hair 2 months after clipping in the untreated-hypothyroid dogs. Untreated-hypothyroid dogs had a greater number of follicles in telogen and fewer hair shafts (ie, a greater number of hairless telogen follicles) than did the control group. The control dogs had a greater number of telogen follicles but the same number of hair shafts as the treated-hypothyroid group. Treated-hypothyroid dogs had the greatest number of follicles in the growing stage of the hair cycle (anagen). This study suggests that, at least in Beagles, induced hypothyroidism does not affect the pelage as dramatically as has been described in naturally occurring disease. This is because normal Beagles retain hair shafts in follicles for long periods, and the alopecia of hypothyroidism appears to evolve slowly because of the prolongation of this haired telogen stage. The evaluation of thyroxine-treated hypothyroid dogs demonstrates that thyroid hormone supplementation of Beagle dogs with induced hypothyroidism stimulates hair growth.     

Effect of hyaluronidase on aqueous outflow resistance in normotensive and glaucomatous eyes of dogs.

The anterior chambers in 16 dogs with normotensive eyes and 3 Beagles with glaucomatous eyes were treated with 0, 25, 50, or 100 IU of bovine testicular hyaluronidase. Aqueous outflow resistance was then determined by constant-pressure perfusion of 0.9% NaCl solution for 30 or 60 minutes. In normotensive eyes, 25, 50, or 100 IU of hyaluronidase significantly (P less than 0.02) increased the rate of constant-pressure perfusion compared with that of untreated eyes during 30- or 60-minute perfusions. Treatment of glaucomatous eyes with 25, 50, or 100 IU of hyaluronidase did not significantly increase the rate of constant-pressure perfusion over controls during a 30-minute perfusion. Bovine testicular hyaluronidase at all doses removed the staining of colloidal iron from the trabecular meshwork in normotensive eyes. In Beagles with glaucoma, the trabecular meshworks remained stained with colloidal iron when treated with the hyaluronidase, which suggested that some glycosaminoglycans were resistant to this enzyme's action.     

Comparative disposition of pharmacologic markers for cytochrome P-450 mediated metabolism, glomerular filtration rate, and extracellular and total body fluid volume of Greyhound and Beagle dogs

The purpose of the study was to compare the disposition of pharmacologic markers for cytochrome P-450 (CYP) metabolism, glomerular filtration rate (GFR), and extracellular (ECFV) and total body fluid volumes (TBFV) of Greyhounds and Beagles. Six healthy Greyhound and six healthy Beagle dogs were studied. Antipyrine, a marker for CYP metabolism and TBFV, and inulin, a marker for the GFR and ECFV, were administered i.v. Samples were collected at predetermined times and plasma was analyzed by validated high-pressure liquid chromatography (HPLC) methods. There were no differences in the disposition or pharmacokinetic parameters for inulin between the dog breeds. However, the clearance of antipyrine (mean = 8.33 mL/min/kg) in Greyhounds was significantly slower than Beagles (13.42 mL/min/kg, P = 0.004). The volume of distribution of antipyrine was significantly larger in Greyhounds (0.789 L/kg) than in Beagles (0.644 L/kg, P = 0.01). The half-life of antipyrine was significantly longer in Greyhounds (1.09 h) compared with Beagles (0.55 h, P = 0.002). The in vitro plasma protein binding of antipyrine was significantly less in Greyhounds (28%) compared with Beagles (40.3%, P = 0.008). Greyhounds exhibited significantly slower CYP metabolism, higher TBFV, and lower in vitro protein binding of antipyrine compared with Beagles. No differences in GFR or ECFV were found.     

Bone marrow mastocytosis in dogs with myelosuppressive monocytic ehrlichiosis (Ehrlichia canis): a retrospective study

BACKGROUND: Bone marrow mastocytosis has been reported rarely in naturally occurring canine monocytic ehrlichiosis (CME). OBJECTIVES: The aims of the present study were to estimate the prevalence and magnitude of bone marrow mastocytosis in a case series of dogs with natural CME and to assess the association, if any, between mastocytosis and the clinical severity of the disease. METHODS: Seventy-six dogs with confirmed CME (Ehrlichia canis) were included in the study. Affected dogs were allocated into group A (n = 51) without bone marrow hypoplasia and group B (n = 25) with bone marrow hypoplasia. Twenty clinically healthy Beagles not previously exposed to E canis served as controls (group C). The main inclusion criteria for group A were documentation of normocellular to hypercellular bone marrow and complete clinical cure following a 4-week treatment with doxycycline, while those for group B were bone marrow hypoplasia and lack of response to doxycycline. Bone marrow aspirate smears from all 96 dogs were Giemsa-stained and examined for the presence of mast cells, which were calculated as a percentage of 1,000 nucleated cells (NCs). The prevalence of mastocytosis was compared among the 3 groups by the Pearson's chi-square test. RESULTS: Bone marrow mastocytosis (>0.1% of NCs) was found in 5 (20%) dogs in group B (range, 0.5-2.5% of NCs; median, 1% of NCs). One dog in each of groups A and C had 0.1% mast cells in the marrow. The prevalence of bone marrow mastocytosis in dogs in group B was significantly higher (P = .004) than in groups A and C. CONCLUSION: Bone marrow mastocytosis can be seen in a substantial number of dogs with E canis-induced myelosuppression.     

Comparison of postprandial and ceruletide serum bile acid stimulation in dogs

BACKGROUND: Postprandial (PP) serum bile acid (SBA) stimulation is an important test for detecting hepatic dysfunction in dogs. However, this test is influenced by numerous variables, and a standardized approach using an injectable cholecystokinin analog (ceruletide) may be advantageous. HYPOTHESIS: Ceruletide SBA stimulation test is more sensitive than PP SBA stimulation in dogs. ANIMALS: Animals with portosystemic shunt (PSS) (n = 11) and dogs with upper respiratory disease (URD) (n = 9) were investigated. Healthy dogs (n = 13) and dogs with other diseases (n = 17) served as controls. METHODS: All dogs underwent SBA stimulation with food and ceruletide. Stimulation blood samples were drawn at 60/120 minutes and 20/30/40 minutes, respectively. Results were compared statistically, and the sensitivity and specificity were determined with receiver-operating characteristic curves. RESULTS: Stimulated SBA were significantly higher in both study groups than in controls. For dogs with PSS, the sensitivity and specificity (>35 micromol/L) were 100% postprandially (120 minutes) and 91 and 100%, respectively, postceruletide (30 minutes). The difference between these values was not statistically significant. For dogs with URD, the sensitivity and specificity (>22 micromol/L) were 44 and 88% postprandially (120 minutes) and 100 and 88% postceruletide (30 minutes). CONCLUSIONS AND CLINICAL IMPORTANCE: Ceruletide SBA stimulation circumvents exogenous and endogenous influences associated with PP SBA stimulation. The results indicate that ceruletide SBA stimulation performs as well as PP SBA stimulation in dogs with PSS and is more sensitive for the detection of hepatic dysfunction in dogs with URD.     

Clinical and pathologic comparison of acute leptospirosis in dogs caused by two strains of Leptospira kirschneri serovar grippotyphosa

OBJECTIVE: To develop a method for inducing acute leptospirosis in dogs. ANIMALS: 31 nine-week-old female Beagles. PROCEDURE: Beagles were randomly assigned to 2 inoculation groups or a control group. Dogs were inoculated on 3 successive days by conjunctival instillation of 5 x 10(7) cells of Leptospira kirschneri serovar grippotyphosa strain 82 (12 dogs) or strain RM 52 (14 dogs). Control dogs (n = 5) were similarly inoculated with sterile leptospiral culture media. Clinical signs, clinicopathologic variables, anti-leptospiral antibody titers, and evidence of leptospires in tissues and body fluids were evaluated. Dogs were euthanatized and necropsied on days 7, 14, 22, or 28 after inoculation or as required because of severe illness. RESULTS: Clinical signs in infected dogs included conjunctivitis, lethargy, diarrhea, dehydration, vomiting, and icterus. Consistent clinicopathologic alterations included azotemia, hyperphosphatemia, increased anion gap, hyperbilirubinemia, and an increase in alkaline phosphatase activity. Leptospires were cultured from the kidneys (11/12), urine (6/9), aqueous humor (9/12), blood (12/12), and liver (12/12) of dogs inoculated with strain 82. Only 3 of 14 dogs became infected after inoculation with strain RM 52. Histopathologic lesions in infected dogs included interstitial nephritis, renal tubular degeneration and necrosis, pulmonary hemorrhage, and hepatic edema and perivasculitis. CONCLUSIONS AND CLINICAL RELEVANCE: Conjunctival exposure to L kirschneri serovar grippotyphosa strain 82 resulted in acute leptospirosis in all inoculated dogs, but only 3 of 14 dogs inoculated with strain RM 52 became infected. This method of infection by serovar grippotyphosa can be used to study the pathogenesis and prevention of leptospirosis in dogs.     

Preliminary evaluation of Lactobacillus rhamnosus strain GG,a potential probiotic in dogs

Lactobacillus rhamnosus strain GG (LGG) has been studied extensively as a probiotic in humans. However, the ability of an organism to survive passage through the intestinal tract and exert beneficial effects cannot be directly extrapolated between species. This study evaluated the ability of LGG to survive gastrointestinal transit in dogs and assessed whether oral administration of LGG is safe, in order to determine whether studies evaluating the efficacy of LGG in the treatment of canine disease are indicated. Dogs were divided into 5 groups receiving doses of 0 (control group, n = 4), 1 x 10(9) (group 1, n = 8), 1 x 10(10) (group 2, n = 8), 5 x 10(10) (group 3, n = 8) and 5 x 10(11) (group 4, n = 4) colony forming units per day, orally, for 5 days. Lactobacillus rhamnosus GG was detected in the feces of 4/8 dogs in groups 1 and 2, 5/8 dogs in group 3, 4/4 dogs in group 4, and 0/4 dogs in the control group. Fecal colonization was significantly greater in group 4 than in any other group (P < 0.001). Differences between groups 1, 2, and 3 were not significant. No adverse effects were noted. Fecal colonization of LGG in dogs is somewhat variable; however, clinical studies are indicated to evaluate this organism in the treatment and prevention of canine disease.     

Steady-state pharmacokinetics of oral sustained-release morphine sulphate in dogs

The pharmacokinetics of steady-state oral sustained-release morphine sulphate (OSRMS) were studied in dogs. Beagles ( n = 6) were randomly assigned to one of two treatment groups. Treatments included 15 mg OSRMS every 8 h for 4 days, or 15 mg OSRMS every 12 h for 4 days. Serum samples, drawn at intervals for the final 24 h of drug administration were analysed for morphine concentration using radioimmunoassay. Pharmacokinetic analysis revealed that there were no significant differences between trough serum concentrations for the concentration–time curves within either treatment group, indicating that steady-state pharmacokinetics had been achieved. There were no significant differences in time to maximum serum concentration among the three sections of the concentration–time curve for the 8-h group or between the two sections of the curve for the 12-h group. Area under the concentration–time curve and maximum serum concentrations were significantly greater for the section of the curve following dosing at 7:30 h than following dosing at 19:30 h in the 12-h treatment group. This chronopharmacokinetic variability was not present in the 8-h treatment group. OSRMS provides sustained periods of elevated serum concentrations following administration every 8 or 12 h at a clinically applicable dosage. The clinical implications of the chronopharmacokinetic variability seen with 12-hourly administration are not known. This formulation has potential for the treatment of chronic pain in dogs, but further studies of efficacy and safety following long-term administration are required.     

Acute, subchronic, and chronic toxicity of ecadotril in dogs

OBJECTIVE: To determine the toxicity of ecadotril in dogs. ANIMALS: 74 healthy 4- to 11-month-old Beagles. PROCEDURE: To determine acute toxicity, ecadotril (2,000 mg/kg of body weight, PO) in a gelatin capsule was administered once to 2 dogs, and dogs were observed for 2 weeks. To determine subchronic and chronic toxicity, ecadotril was administered every day for 3 months (50 mg/kg [n = 8], 100 mg/kg [8], 300 mg/kg [12]) and 12 months (25 mg/kg [n = 8], 50 mg/kg [8], 100 mg/kg [8]), respectively. Dogs in control groups (n = 12 or 8) received an empty gelatin capsule. Physical examinations, CBC, plasma biochemical analyses, and urinalyses were performed before and at various times during each experiment. Dogs were euthanatized at the end of each experiment, and necropsies were performed. RESULTS: Dogs that received 1 dose of 2,000 mg of ecadotril/kg developed nonspecific clinical signs of toxicosis. Dogs that received 300 mg of ecadotril/kg/d for 3 months developed pronounced anemia, bone marrow suppression, and some evidence of liver impairment. There was no evidence of an effect accumulated over time, and reversibility of toxic effects was evident. Dogs that received < or =100 mg of ecadotril/kg/d for 3 or 12 months tolerated treatment without apparent effect. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of acute toxicity of a single high dose of ecadotril in dogs was low. The no-observable adverse effect level of ecadotril following daily oral administration was 100 mg/kg/d; repeated administration of 300 mg/kg/d revealed the hematopoietic system as the primary toxicologic target.     

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.     

Effects of atracurium on intraocular pressure, eye position, and blood pressure in eucapnic and hypocapnic isoflurane-anesthetized dogs

OBJECTIVE: To determine effects of atracurium on intraocular pressure (IOP), eye position, and arterial blood pressure in eucapnic and hypocapnic dogs anesthetized with isoflurane. ANIMALS: 16 dogs. PROCEDURE: Ventilation during anesthesia was controlled to maintain Paco2 at 38 to 44 mm Hg in group- I dogs (n = 8) and 26 to 32 mm Hg in group-II dogs (8). Baseline measurements for IOP, systolic, diastolic, and mean arterial blood pressure, central venous pressure (CVP), and heart rate (HR) were recorded. Responses to peroneal nerve stimulation were monitored by use of a force-displacement transducer. Atracurium (0.2 mg/kg) was administered i.v. and measurements were repeated at 1, 2, 3, and 5 minutes and at 5-minute intervals thereafter for 60 minutes. RESULTS: Atracurium did not affect IOP, HR, or CVP Group II had higher CVP than group I, but IOP was not different. There was no immediate effect of atracurium on arterial blood pressure. Arterial blood pressure increased gradually over time in both groups. Thirty seconds after administration of atracurium, the eye rotated from a ventromedial position to a central position and remained centrally positioned until 100% recovery of a train-of-four twitch response. The time to 100% recovery was 53.1 +/- 5.3 minutes for group I and 46.3 +/- 9.2 minutes for group II. CONCLUSIONS AND CLINICAL RELEVANCE: Atracurium did not affect IOP or arterial blood pressure in isoflurane-anesthetized dogs. Hyperventilation did not affect IOP or the duration of effect of atracurium.     

Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990).

The diagnostic efficacy of serum alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities was examined, using the records of 270 dogs initially suspected of having hepatobiliary disease on the basis of history, findings on physical examination, results of baseline screening tests, or any combination of these data. Histologic examination of hepatic tissue was performed in each dog. Sixty-three dogs did not have histologic evidence of hepatobiliary disease and served as the control group. On the basis of diagnosis, dogs were assigned to 1 of 8 groups: dogs with cirrhosis (n = 34), steroid hepatopathy (n = 16), hepatic neoplasia (primary and secondary, n = 36), chronic hepatitis (n = 14), chronic passive congestion (n = 5), hepatic necrosis (n = 17), portosystemic vascular anomaly (n = 35), and cholestasis (extrahepatic bile-duct obstruction and intrahepatic cholestasis, n = 50). Of the 207 dogs with hepatobiliary disease, 29 (14%) had normal ALP and GGT activities, 31 (15%) had normal ALP activity, and 112 (54%) had normal GGT activity. Of the 63 control dogs, 29 (46%) had normal serum ALP and GGT activities, 32 had normal ALP activity (ALP specificity, 51%), and 55 had normal GGT activity (GGT specificity, 87%). The specificity of ALP and GGT in parallel (positive result = result of either test abnormal) was 46%, and in series (positive result = results of both tests abnormal) was 91%. The highest median activities of ALP developed in dogs with cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis. The highest median activities of GGT developed in dogs with steroid hepatopathy, cholestasis, and hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of collagenase-induced mitral valve regurgitation in dogs

OBJECTIVE: To investigate the hemodynamic changes induced by injecting collagenase into the mitral valve to induce mitral valve regurgitation (MVR) in dogs. ANIMALS: 9 healthy Beagles. PROCEDURE: Dogs were randomly assigned to 3 groups: control (saline [0.9% NaCl] solution; n = 3), single collagenase injection (C1; 3), and 2 collagenase injections (C2; 3). Open-heart surgery was performed, and saline or collagenase solutions were injected into the mitral valve. Before and weekly for 11 weeks after surgery, radiography, echocardiography, and phonocardiography were performed. Mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure (mPAWP) were measured before and 11 weeks after surgery. Postmortem examinations were performed after dogs were euthanatized. RESULTS: No changes were detected in the control group during the 11-week follow-up period. A systolic murmur and MVR developed 1 week after surgery in groups C1 and C2. The murmur changed from a protosystolic to a pansystolic murmur, and left atrial diameter and the left atrial-to-aortic root diameter ratio increased with time. Mean pulmonary arterial pressure and mPAWP were greater 11 weeks after surgery in groups C1 and C2, compared with presurgery values. During necropsy, tissue loss was detected in the mitral valve at the site of collagenase injection. Degree of regurgitation corresponded to lesion size. CONCLUSIONS AND CLINICAL RELEVANCE: Injection of collagenase into the mitral valve of healthy dogs induced MVR, and dogs with MVR developed progressive hemodynamic changes without acute overload. Collagenase-induced MVR may be an appropriate model for evaluation of prognostic markers of idiopathic MVR in dogs.     

Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs

Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n=5), 0.8 U/kg (n=10), or 0.8 U/kg at three separate sites (n=6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose-lowering effect was nonlinear. For single-site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5-10 h), time to glucose nadir was 14 h (5 to >24 h), and duration of action was >24 h (16 to >24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. This insulin may be an alternative treatment option for diabetic dogs.     

Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study

BACKGROUND: Pimobendan (PIMO) is an inodilator that may have some beneficial effects in canine degenerative mitral valve disease (MVD). However, little information is available about its cardiac effects in dogs without systolic myocardial dysfunction. HYPOTHESIS: Compared to benazepril (BNZ), an angiotensin-converting enzyme inhibitor, PIMO may worsen valve regurgitation in early canine MVD. ANIMALS: Twelve Beagles with asymptomatic MVD were randomized into 2 groups (n = 6) receiving BNZ or PIMO at dosages of 0.25 mg/kg PO q24h and q12h respectively, for 512 days. METHODS: The study followed a blinded, randomized, prospective, and parallel group design. After day 512, the dogs were necropsied, and cardiac histopathology was performed in a blinded manner. RESULTS: A significant treatment effect was observed as soon as day 15 with increased systolic function in the PIMO group by comparison to baseline value as assessed by fractional shortening (P < .0001) and tissue Doppler variables (P = .001). Concurrently, the maximum area and peak velocity of the regurgitant jet signal increased (P < .001), whereas these variables remained stable in the BNZ group. Histologic grades of mitral valve lesions were more severe in the PIMO group than in the BNZ group. Moreover, acute focal hemorrhages, endothelial papillary hyperplasia, and infiltration of chordae tendinae with glycosaminoglycans were observed in the mitral valves of dogs from the PIMO group but not in those of the BNZ group. CONCLUSIONS AND CLINICAL IMPORTANCE: PIMO has adverse cardiac functional and morphologic effects in dogs with asymptomatic MVD. Additional investigation in dogs with symptomatic MVD is now warranted.