Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P less than 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P less than 0.05) reduced and reserve function was markedly (P less than 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.     

Effect of serum storage, anti-inflammatory oral doses of prednisone, and spontaneous hyperadrenocorticism on serum glutamate dehydrogenase activity in dogs

BACKGROUND: Glutamate dehydrogenase (GLDH) is a mitochondrial enzyme with highest activity in periacinar hepatocytes. It is reported to be a sensitive indicator of hepatic injury; however, results of studies regarding tissue specificity are contradictory. OBJECTIVES: The purpose of the study reported here was to examine the effect of 3 factors on serum GLDH activity in dogs: serum storage, anti-inflammatory oral doses of prednisone, and spontaneous hyperadrenocorticism (HAC). METHODS: Stability of enzyme activity was determined by comparing serum samples stored at approximately 20 degrees C, 4 degrees C, and 20 degrees C for 4, 24, 48, and 72 hours, 1 week, and 6 months. To determine whether orally administered prednisone affected GLDH activity, the median difference in serum GLDH activity was compared between 5 untreated control dogs and 8 dogs that had received a tapering oral dose of prednisone. Lastly, GLDH enzyme activity was compared between 17 dogs with HAC and 16 age-matched controls. RESULTS: GLDH activity remained stable for 48 hours, 1 week, and 6 months, in serum stored at approximately 20 degrees C, 4 degrees C, and 20 degrees C, respectively. The median change in GLDH activity was not significantly different between dogs receiving prednisone and controls; however, dogs with HAC had significantly higher values than those of age-matched controls. CONCLUSIONS: Serum samples should be maintained at 4 degrees C if analysis of GLDH activity will be delayed by >48 hours; serum stored at 20 degrees C yields reliable results for up to 6 months. Serum GLDH activity was not increased in most dogs receiving short-term, anti-inflammatory oral doses of prednisone, in contrast to its increased activity in dogs with HAC.     

Adrenocortical suppression in dogs on daily and alternate-day prednisone administration

Three groups of eight normal dogs each were orally given prednisone at doses of 0.22 mg/kg of body weight/day, 0.55 mg/kg/day, or 1.1 mg/kg on alternate mornings. Four dogs served as nontreated controls. Samples were obtained from members of each group to determine baseline serum cortisol and ACTH-stimulated cortisol values and histologic features in the lateral thoracic skin before prednisone administration, and after 1, 2, 3, and 4 weeks of administration. Some animals from each group were necropsied after 1, 2, 3, and 4 weeks of prednisone administration. Each course of prednisone administration resulted in adrenocortical atrophy and hypofunction, but adrenocortical suppression was less severe and slower in onset in the group given prednisone on alternate days. Extra-adrenal effects observed were atrophy of the skin and focal, fatty change of the liver. These changes were most evident in dogs given daily pharmacologic doses of prednisone (0.55 mg/kg/day). Fewer extra-adrenal effects were observed in dogs given alternate-day therapy. There were no extra-adrenal lesions in the dogs given equivalent glucocorticoid replacement doses (0.22 mg/kg/day).     

Hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves

OBJECTIVE: To evaluate hematologic and serum biochemical changes in Salmonella ser Typhimurium-infected calves. ANIMALS: 16 male 3- to 4-week-old dairy calves. PROCEDURE: 13 calves were experimentally infected with S Typhimurium (strains IR715 and CS401, which are derivatives of ATCC 14028), and 3 calves were uninfected controls. Several hematologic and serum biochemical parameters were measured. RESULTS: Hematologic changes included increases in PCV, RBC count, and hemoglobin concentration, associated with a transitory leukopenia characterized by neutropenia and lymphopenia. Biochemical findings included hypoglycemia, increased BUN, creatinine, and fibrinogen concentrations, and decreased sodium, total CO2, calcium, total protein, and albumin concentrations. Increased total bilirubin concentration associated with decreased conjugated bilirubin concentration was also observed. No significant changes in aspartate aminotransferase, gamma-glutamyltranspeptidase, alkaline phosphatase, and creatinine kinase activities were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Experimental salmonellosis of calves results in marked to severe dehydration, accompanied by metabolic acidosis, hypoglycemia, and an acute inflammatory response associated with increased fibrinogen concentrations and severe neutropenia immediately after inoculation.     

Hematologic changes associated with weekly low-dose cisplatin administration in dogs

This study prospectively describes the systemic toxicity of cisplatin (20 mg/m(2),IV) when given in weekly doses prior to localized irradiation in dogs with solid malignancies. Eleven dogs received a total of 54 weekly doses of cisplatin. Two dogs did not complete the 5-week protocol due to progressive disease and two dogs received 6 weekly doses of cisplatin. Repeated administration of cisplatin caused a significant decline in the leukocyte count, segmented neutrophil count, and platelet count. These changes were related to the number of cisplatin doses. The dogs did not have any significant alteration of blood urea nitrogen, serum creatinine, or urine specific gravity during the treatment period. Weekly low-dose cisplatin, as used in this study, is safe for use in tumor-bearing dogs. However, the significant decline in the leukocyte, segmented neutrophil, and platelet counts in these 11 dogs suggest that cisplatin prescribed at 20 mg/m(2) IV once per week should not exceed five consecutive treatments.     

Effects of short courses of different doses of prednisone and dexamethasone on serum third component of complement (C3) levels in dogs.

The effect of different doses of prednisone and dexamethasone on serum C3 levels was determined in 35 dogs. Dogs in Group A (n = 15) were administered prednisone (1.1 mg/kg/day) for 14 days; dogs in Group B (n = 10) were given prednisone at 2.2 mg/kg/day for 7 days; dogs in group C (n = 10) were administered dexamethasone (0.25 g/kg/day) for 7 days. Serum C3 concentrations were determined using a sandwich ELISA in samples obtained before and after glucocorticoid administration. Concentrations were expressed as a percentage of a reference standard. No statistically significant differences were found after glucocorticoid administration in all groups. Thus, short-term administration of prednisone and dexamethasone at commonly used doses did not result in significantly lower serum C3 levels.     

Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring in hypothyroid dogs

It is not uncommon for a hypothyroid dog to be receiving concurrent corticosteroids. As hypothyroid dogs receiving thyroid supplement need periodic monitoring, knowledge of whether prednisone alters thyroid hormone concentrations would be useful to determine whether testing can or should be done while the dog is receiving therapy and whether dose adjustments are appropriate. In this study, the effect of short-term anti-inflammatory prednisone was determined in dogs with naturally occurring hypothyroidism. Eight adult dogs were given prednisone (1.0 mg/kg, orally) daily for 7 days and then on alternate days for 14 days. Serum total thyroxine (T(4) ), free T(4) (fT(4) ), and thyroid-stimulating hormone (TSH) were measured on days 7, 21 and 28 and compared with baseline data. Total T(4) concentrations were significantly decreased after 7 days of anti-inflammatory prednisone, but were not significantly altered from baseline on days 21 or 28. Free T(4) and TSH concentrations were not significantly altered from baseline at any point during the study. Two dogs had decreased total T(4) concentrations on day 7, which may have resulted in an alteration in thyroid supplementation. Results showed that administration of prednisone at a dosage of 1 mg/kg, orally, once daily for 7 days decreased total T(4) , while fT(4) was unchanged, suggesting that fT(4) may be less affected by daily prednisone administration. Anti-inflammatory doses of prednisone administered every other day did not interfere with thyroid hormone monitoring.     

Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized dogs

OBJECTIVE: To determine the incidence and type of alterations in heart rate (HR), peak systolic blood pressure (PSBP), and serum biochemical variables (total bilirubin, BUN, and creatinine concentrations) associated with IV administration of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and gadolinium dimeglumine (GD) contrast media in anesthetized dogs. ANIMALS: 280 anesthetized dogs undergoing cross-sectional imaging. PROCEDURES: HR and PSBP were recorded at 5-minute intervals for 20 minutes for untreated control dogs and dogs that received IIC, NIC, or GD contrast medium. The development of an HR of < 60 beats/min or > 130 beats/min that included a > or = 20% change from baseline was considered a response. The development of PSBP of < 90 mm Hg or > 160 mm Hg that included a > or = 20% change from baseline was considered a response. Pre- and postcontrast serum biochemical values were recorded. Results-Of dogs receiving IIC medium, 3% (3/91) had a response in HR and 4% (4/91) had a response in PSBP at > or = 1 time points. None of the dogs receiving NIC medium had a response in HR; 1 of 16 had a response in PSBP. Of dogs receiving GD contrast medium, 1% (1/92) had a response in HR and 4% (4/92) had a response in PSBP. Of control dogs, 2% (2/81) had a response in HR and 4% (3/81) had a response in PSBP. No serum biochemical alterations were observed. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of contrast media in anesthetized dogs caused moderate bradycardia, tachycardia, hypotension, or hypertension.     

Cardiovascular and respiratory effects of propofol administration in hypovolemic dogs.

Cardiopulmonary effects of propofol were studied in hypovolemic dogs from completion of, until 1 hour after administration. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 6 mg of propofol/kg of body weight was administered IV to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to propofol administration, oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after propofol administration, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen utilization ratio, venous admixture, and arterial and mixed venous carbon dioxide tensions increased, whereas mean arterial pressure, arterial oxygen tension, mixed venous oxygen content, arterial and mixed venous pH decreased from values measured prior to propofol administration. Fifteen minutes after propofol administration, mixed venous carbon dioxide tension was still increased; however by 30 minutes after propofol administration, all measurements had returned to values similar to those measured prior to propofol administration.     

Hematologic changes induced by intravenous administration of diacetoxyscirpenol in pigs, dogs, and calves

Diacetoxyscirpenol (DAS) was given IV to pigs (0, 0.5, and 1.0 mg/kg of body weight), cattle (0 and 0.5 mg/kg), and dogs (0 and 0.5 mg/kg). Blood was collected and hemograms were done at 0.5-hour intervals for 8 hours. The animals were euthanatized at 8 hours after treatment, and bone marrow samples were taken and examined by light microscopy. Moderate to severe necrosis of bone marrow hematopoietic elements was found in animals given DAS. The sequential increase in the type and number of abnormal cells in the blood suggested a successive destruction of the hematopoietic elements. A marked left shift in the neutrophil population was found in animals given DAS. Metarubricytes and large platelets were found in the blood of animals given DAS. Lymphocytes were replaced with immature cells. Pathologic changes were most severe in the pigs given a dosage of 1.0 mg of DAS/kg. The order of species sensitivity to DAS was pigs greater than dogs much greater than cattle.     

Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs.

The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.     

Effects of phenobarbitone on serum biochemical tests in dogs

OBJECTIVES: To investigate effects of phenobarbitone on serum activities of alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transferase and concentrations of bilirubin, albumin, cholesterol and total protein in dogs. ANIMALS: Ten crossbreed experimental dogs and 10 client-owned dogs of mixed breeds treated chronically with phenobarbitone to control seizures. PROCEDURES: Experimental dogs were allocated to treatment (6 mg/kg oral phenobarbitone, n = 6) and control (no treatment, n = 4) groups in which serum biochemical tests were performed at intervals during a 3-month period. Biochemical tests were performed once on the 10 epileptic dogs. RESULTS: Phenobarbitone caused increased serum alkaline phosphatase activity but did not affect gamma-glutamyl transferase activity or bilirubin, cholesterol, albumin and total protein concentrations. Phenobarbitone had minimal effect on alanine aminotransferase activity. CONCLUSIONS: Individual dogs treated with phenobarbitone may have small increases in serum alanine aminotransferase activity and variable increases in alkaline phosphatase activity but are unlikely to have alterations in gamma-glutamyl transferase activity or bilirubin, cholesterol, albumin or total protein concentrations.     

Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs.

OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.     

The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete blood count (CBC)and flow cytometry were collected prior to the administration of any drugs and again after 14 d of azathioprine, prednisone or azathioprine and prednisone. Peripheral blood mononuclear cells were isolated using density centrifugation and were incubated with monoclonal antibodies reacting with CD4+, CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P < 0.05) decreases in all SIg levels, all lymphocyte subpopulations and erythrocyte numbers, and had an increase in neutrophil counts. Prednisone and azathioprine-treated dogs had significant (P < 0.05) decreases in serum IgG levels and Thy-1+ and CD8+ lymphocyte subpopulations, with an increase in the CD4:CD8. These dogs also had a significant decrease in erythrocyte number and a significant increase in the monocyte count. These findings suggest that azathioprine and prednisone in combination or prednisone alone may be useful for the treatment of T cell-mediated diseases since decreased circulating T cell levels were demonstrated following treatment. The combination of drugs or azathioprine alone may not be appropriate for treatment of acute or autoantibody-mediated immune disease, because SIg levels were minimally affected by treatment.     

Hematologic and bone marrow changes after short- and long-term administration of two recombinant bovine granulocyte colony-stimulating factors.

Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid:erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF.