Predicted mean corpuscular volume as an indicator of bone marrow iron in anemic dogs

A predicted mean corpuscular volume (PMCV) was calculated from the reticulocyte percentage and compared to the actual mean corpuscular volume for the purpose of determining bone marrow iron depletion in the dog. A difference of greater than 10 fl between the pMCV and the actual measured MCV accurately predicted the absence of stainable iron in bone marrow aspirates (sensitivity 86%, specificity 93%). The difference (Diff) between the predicted and actual measured MCV may also be a valuable method for following response to iron therapy in dogs with iron deficiency anemia without the necessity for repeated bone marrow examination. The predicted MCV may be useful in determining which patients are not at risk for canine iron deficiency.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Persistent polyuria in two dogs following adrenocorticolysis for pituitary‐dependent hyperadrenocorticism

Summary

In two dogs with pituitary‐dependent hyperadrenocorticism, adrenocorticolysis with o,p'‐DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water‐deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.     

Customization of Advia 120 thresholds for canine erythrocyte volume and hemoglobin concentration,and effects on morphology flagging results

This study sought to develop customized morphology flagging thresholds for canine erythrocyte volume and hemoglobin concentration [Hgb] on the ADVIA 120 hematology analyzer; compare automated morphology flagging with results of microscopic blood smear evaluation; and examine effects of customized thresholds on morphology flagging results. Customized thresholds were determined using data from 52 clinically healthy dogs. Blood smear evaluation and automated morphology flagging results were correlated with mean cell volume (MCV) and cellular hemoglobin concentration mean (CHCM) in 26 dogs. Customized thresholds were applied retroactively to complete blood (cell) count (CBC) data from 5 groups of dogs, including a reference sample group, clinical cases, and animals with experimentally induced iron deficiency anemia. Automated morphology flagging correlated more highly with MCV or CHCM than did blood smear evaluation; correlation with MCV was highest using customized thresholds. Customized morphology flagging thresholds resulted in more sensitive detection of microcytosis, macrocytosis, and hypochromasia than default thresholds.     

Effect of dietary chloride content on the elimination of bromide by dogs

The effect of dietary chloride content (0·2, 0·4 and 1·3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg⁻¹ was evaluated in normal beagles. Increasing the dietary chloride content from 0·2 to 1·3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 ± 22 days to 24 ± 7 days. The mean area under the concentration curve ( ) for dogs fed 1·3 per cent chloride was significantly smaller than the for dogs fed 0·2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (C_max) or on the time (T_max) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg⁻¹ of bromide were significantly lower in dogs fed 1·3 per cent chloride (310 ± 150 mg litre⁻¹) than in dogs fed 0·2 per cent chloride (1950 ± 1140 mg litre⁻¹). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1·3 per cent chloride (43 ± 13 mg kg⁻¹) were almost twice as high as the dose estimated for dogs fed 0·4 per cent chloride (22 ± 3 mg kg⁻¹) and nearly three times as high as the dose estimated for dogs fed 0·2 per cent chloride (15 ± 4 mg kg^−l). These differences were statistically significant (P=0·002).     

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (C_SS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min⁻¹ kg⁻¹, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min⁻¹ kg⁻¹, respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median C_SS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median C_SS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on C_SS (therapeutic drug monitoring) and treatment failure should be considered.     

Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Differentiation of dogs with regenerative and non-regenerative anaemia on the basis of their red cell distribution width and mean corpuscular volume

The red blood cell distribution width (RDW), which provides a quantitative measure of the heterogeneity of the red cell population (anisocytosis) in the peripheral blood, the mean corpuscular volume (MCV) and a regression model combining both variables were used to assess their predictive accuracy in differentiating 51 dogs with regenerative anaemia from 92 dogs with non-regenerative anaemia, which had been diagnosed on the basis of the corrected reticulocyte count A classification tree analysis was constructed to generate an optimum set of diagnostic rules to differentiate between the two types of anaemia. Seventy-four dogs with a normal haemogram were used as controls. An increase of 1 per cent in the RDW and of 1 fl in the MCV increased the odds of an anaemic dog suffering from regenerative anaemia by factors of 1.3 and 1.14, respectively. By the classification tree, 78 per cent of anaemic dogs with a RDW of 16.25 per cent or less would be expected to have non-regenerative anaemia. With a RDW over 16.25 per cent, an MCV of 68.2 fl was the cut-off between dogs expected to have regenerative (71 per cent) or non-regenerative (75 per cent) anaemia. The RDW and MCV are measured by most automatic haematology analysers and may give the first indication of the bone marrow response of an anaemic dog. However, different electronic counters give different normal values of the RDW and MCV.     

Comparison of two automated multi-channel blood cell counting systems for analysis of blood of common domestic animals

An automated, multi-channel blood cell counting system (S-Plus) was compared to a reference counting system using blood samples from 187 animals of four species. The standard red cell bath aperture current of 150 volts (V) was used during analysis of 75% of the samples. At this setting, all samples with a Mean Corpuscular Volume (MCV) greater than 50 fl had accurate erythrocyte counts. As the MCV decreased below 50 fl, the severity of false low erythrocyte counts and false high MCV values increased. The remaining 25% of samples were analyzed with the red cell bath aperture current increased to 200 V. At this setting, only 5% or less of erythrocytes from animals with normal MCV values(>36 fl)were below the erythrocyte threshold. The red cell distribution width values provided by the S-Plus indicated that equine and bovine erythrocytes have greater anisocytosis than canine and feline erythrocytes. Leukocyte counts were significantly lower on the S-Plus (p<0.01). Canine and equine samples most frequently had platelet size distribution within the S-Plus platelet counting threshold window. Electronic whole blood platelet counting appeared unsatisfactory in cats due to large platelet size and erythrocyte-platelet size overlap. Small platelet size in cattle indicated that further modifications of the red cell bath aperture current would be required to count and size platelets in this species. Following electronic modifications, this state-of-the-art system appears adaptable to hematologic profiling in most species.     

Hematologic and biochemical abnormalities indicating iron deficiency are associated with decreased reticulocyte hemoglobin content (CHr) and reticulocyte volume (rMCV) in dogs

BACKGROUND: The ADVIA 120 automated hematology system uses low- and high-angle light scatter to determine individual RBC and reticulocyte volume and hemoglobin (Hgb) concentration. Current hematologic and biochemical markers of iron status in the dog are insensitive, and results may be highly variable, especially in the presence of concurrent disease (ie, inflammation, neoplasia). Reticulocyte Hgb content (CHr) has proven useful in detecting early iron deficiency and iron deficiency masked by concurrent disease in human patients. OBJECTIVES: The purpose of this study was to retrospectively investigate the association of low CHr and reticulocyte MCV (rMCV) with hematologic and biochemical abnormalities indicative of iron deficiency in canine patients. METHODS: Reference intervals for CHr and rMCV were established on a population of 362 hematologically-normal dogs using standard methods. CBC and serum biochemical results from 833 dogs at Colorado State University Veterinary Teaching Hospital were retrospectively evaluated. The prevalence of decreased CHr and rMCV values was determined based on the reference intervals. Hematologic (HCT, MCV) and biochemical (serum Fe concentration, percent saturation of transferrin [% sat]) values were compared among dogs with low CHr (n=58), low rMCV (n=50), and control dogs (cohort groups from the initial population) using a Fisher exact test. RESULTS: Reference intervals were 22.3-27.9 pg for CHr and 77.8-100.2 fL for rMCV. Seven percent (n=58) of dogs in the hospital population had low CHr and 6% (n=50) had low rMCV based on the reference values. Dogs with low CHr had significantly lower HCT, MCV, serum Fe, and % sat values than did control dogs. In addition, dogs with low CHr or low rMCV values had a higher frequency of microcytosis, anemia, low serum Fe concentration, and low % sat than did control dogs. CONCLUSION: Low CHr and low rMCV are associated with hematologic and serum biochemical abnormalities indicative of iron deficiency. CHr and rMCV hold promise as noninvasive, cost-effective measures of iron status in the dog.     

Persistent polyuria in two dogs following adrenocorticolysis for pituitary-dependent hyperadrenocorticism

In two dogs with pituitary-dependent hyperadrenocorticism, adrenocorticolysis with o.p'-DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water-deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.     

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs

Objective— To estimate maximum plasma concentration (C_max) and time to maximum plasma (t_max) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate C_max, T_max and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C_max, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean C_max (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C_max below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.     

Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice‐daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time‐course changes in its serum and urine concentrations were determined by high‐performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half‐life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl_R increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including C_max, T_max, AUC_0–216, Cl/F, and A_e0–216 were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying‐diet is administered for the purpose of dissolving or preventing uroliths.     

Is the use of formulae a reliable way to predict the accuracy of genomic selection?

We studied four formulae used to predict the accuracy of genomic selection prior to genotyping. The objectives of our study were to investigate the impact of the parameters of each formula on the values of accuracy calculated using these formulae, and to check whether the accuracies reported in the literature are in agreement with the formulae. First, we computed the marginal distribution of accuracy (by integration) for each parameter of all four formulae: heritability h², reference population size T, number of markers M and number of effective segments in the genome M_e. Then, we collected 145 accuracies and corresponding parameters reported in 13 publications on genomic selection (mainly in dairy cattle), and performed analysis of variance to test the differences between observed and predicted accuracy with effects of formulae and parameters. The variation of accuracy for different values of each parameter indicated that two parameters, T and M_e, had a significant impact and that considerable differences existed between the formulae (mean accuracies differed by up to 0.20 point). The results of our meta‐analysis showed a big formula effect on the accuracies predicted using each formula, and also a significant effect of the value obtained for M_e calculated from N_e (effective population size). Each formula can therefore be demonstrated to be optimal depending on the assumption used for M_e. In conclusion, no rules can be applied to predict the reliability of genomic selection using these formulae.     

Effect of dietary iron content on hematologic and other measures of iron adequacy in dogs

Eighteen 9- to 10-week old Beagles were fed casein-based diets (4,710 kcal of metabolizable energy/kg of body weight) containing either 12, 80, or 160 mg of iron/kg of diet. Growth and feed consumption were monitored throughout the 47-day study. Hematocrit (Hct), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC numbers, erythrocyte protoporphyrin (EP) concentration, serum iron concentration, serum total iron-binding capacity (TIBC), and serum ferritin concentration were determined weekly. Growth rate and feed efficiency were not significantly influenced by dietary iron content. At 14 days, Hb concentration, Hct, MCV, MCH, RBC numbers, and serum iron concentration were significantly (P less than 0.05) lower in dogs fed the 12 mg/kg diet, and remained significantly low for the remainder of the study. Erythrocyte protoporphyrin concentration increased significantly (P less than 0.05) by 14 days in dogs fed the basal diet, and remained significantly high relative to that in dogs of the other dietary groups for the remainder of the study. Serum ferritin concentration decreased in dogs of the group fed the basal diet, with a significant (P less than 0.05) difference beyond day 42. Differences in Hct, MCH, MCV, or hemoglobin, serum iron, serum ferritin, or EP concentration were not found between groups fed 80 and 160 mg of iron/kg of diet. Liver nonheme iron content was significantly (P less than 0.05) affected by dietary iron content.     

Evaluation of a commercially available human C-reactive protein (CRP) turbidometric immunoassay for determination of canine serum CRP concentration

Background: Serum C-reactive protein (CRP) is an acute phase marker in dogs that is useful for the diagnosis and monitoring of inflammatory disease. Rapid, reliable, and automated assays are preferable for routine evaluation of canine serum CRP concentration.
Objective: The aim of this study was to evaluate whether canine serum CRP concentration could be measured reliably using an automated turbidometric immunoassay (TIA) designed for use with human serum.
Methods: A commercially available TIA for human serum CRP (Bayer, Newbury, UK) was used to measure canine serum CRP concentration. Cross-reactivity of antigen was evaluated by the Ouchterlony procedure. Intra-and interassay imprecision was investigated by multiple measurements on canine serum samples and serum pools, respectively. Assay inaccuracy was investigated by linearity under dilution and comparison of methodologies (canine CRP ELISA, Tridelta Development Ltd, Kildare, UK). Then the assay was applied to serum samples from 14 clinically healthy dogs, 11 dogs with neoplasia, 13 with infections, 8 with endocrine or metabolic diseases, and 10 with miscellaneous diseases.
Results: Cross-reactivity between canine serum CRP and the anti-human CRP antibody was found. Intra-and interassay imprecision ranged from 5.2% to 10.8% and 3.0% to 10.2%, respectively. Serum CRP concentration was measured in a linear and proportional manner. There was no significant disagreement and there was linear correlation of the results in the comparison of methodologies, except for a slight proportional discrepancy at low CRP concentrations (<10 μg/mL). Dogs with infections had a significantly higher concentration of serum CRP than did all other dogs, and dogs with neoplasia had a significantly higher concentration of serum CRP than did clinically healthy dogs.
Conclusions: Canine serum CRP concentration can be measured reliably using the commercially available TIA designed for human CRP.     

Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD): AUC_(0–∞) 4.20 ± 1.66 μg·h/mL; C_max 6.64 ± 1.38 μg/mL; V_z 4.80 ± 0.91 L/kg; Cl_t 2.64 ± 0.84 L/h·kg; t_½λ 1.35 ± 0.40 h and MRT 1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD): C_max, 0.30 ± 0.17 and 0.17 ± 0.09 μg/mL; t_max, 1.75 ± 0.76 and 0.69 ± 0.30 h; t_½λ, 2.92 ± 0.79 and 1.53 ± 1.28 h and MRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC₉₀ = 0.5 μg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.     

RADIOGRAPHIC DIAGNOSIS OF MECHANICAL OBSTRUCTION IN DOGS BASED ON RELATIVE SMALL INTESTINAL EXTERNAL DIAMETERS

Mechanical obstruction is a frequent cause of acute vomiting in dogs requiring prompt diagnosis to improve patient management and prognosis. The purpose of this retrospective study was to compare small intestinal radiographic characteristics in dogs with versus without mechanical intestinal obstruction. Fifty dogs with gastrointestinal clinical signs and abdominal radiographs were recruited from hospital record archives and assigned to groups (group 1, obstructive, n = 25; group 2, nonobstructive n = 25). Abdominal radiographs were randomized and independently interpreted by three examiners who were unaware of group status. Intestinal dilation was subjectively scored based on distribution (segmental, regional or diffuse), and severity (absent, mild, moderate or severe). Small intestinal maximal diameter (SI_max), L5 vertebral body height, small intestinal minimal diameter (SI_min), and an estimated average of small intestinal diameters (SI_ave) were measured and three ratios were calculated: SI_max/L5, SI_max/SI_min, and SI_max/SI_ave. Segmental dilation was more prevalent in obstructed dogs for all examiners (P ≤ 0.03) and most nonobstructed dogs had no dilation (P ≤ 0.05). All ratios were higher in obstructed dogs (P < 0.002). Subjective dilation scores and ratio measurements had low interobserver agreement (absent to fair, with kappa values between ?0.06 and 0.57) and reproducibility (coefficients of 0.35–0.61). Findings indicated that dogs with SI_max/L5 ≤ 1.4, SI_max/SI_min ≤ 2, and SI_max/SI_ave ≤ 1.3 values are very unlikely to be mechanically obstructed; dogs with SI_max/L5 ≥ 2.4, SI_max/SI_min ≥ 3.4 and SI_max/SI_ave ≥ 1.9 are very likely obstructed, particularly if segmental dilation (less than 25% of the small intestine) is present. Dogs with ratios falling between these thresholds may need further testing unless other signs justify surgical exploration or endoscopy.     

Cardiovascular function,pulmonary gas exchange and tissue oxygenation in isoflurane-anesthetized,mechanically ventilated Beagle dogs with four levels of positive end-expiratory pressure

ObjectivesTo compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxC_rs), PEEPmaxC_rs + 2 cmH₂O (PEEPmaxC_rs+2), PEEPmaxC_rs + 4 cmH₂O (PEEPmaxC_rs+4), in isoflurane-anesthetized dogs.Study designProspective randomized crossover study.AnimalsA total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation).MethodsThe dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxC_rs, PEEPmaxC_rs+2 or PEEPmaxC_rs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant.ResultsCardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxC_rs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute^–1 m^–2). At 180 and 240 minutes, MAP was lower in PEEPmaxC_rs+4 than in PEEPmaxC_rs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO₂I) was lower in PEEPmaxC_rs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments.Conclusion and clinical relevanceThe use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxC_rs+4. A clinically significant improvement in arterial oxygenation and DO₂I was not observed with PEEPmaxC_rs and PEEPmaxC_rs+2 in comparison with ZEEP, whereas PEEPmaxC_rs+4 decreased DO₂I.     

Pharmacokinetics and oral bioavailability of amoxicillin in chicken infected with caecal coccidiosis

Chicken infected with caecal coccidiosis (Eimeria tenella) was used to evaluate the effect of coccidiosis on the pharmacokinetic and bioavailability of amoxicillin. The level of amoxicillin was estimated by high‐performance chromatography (HPLC) to calculate the pharmacokinetic parameters and oral bioavailability. For i.v. injection of amoxicillin, Vd and CL were 0.29 and 0.27 (mg/kg)/(μg/mL)/h, respectively. Compared with healthy chicken, intravenous injection of amoxicillin in the infected chicken showed higher distribution and elimination constants, delayed clearance and statistically significant higher AUC and MRT. Oral administration in healthy chicken was accompanied by rapid absorption and high bioavailability with T_max, C_max and F about 1.03 h, 3.26 μg/mL and 40.2, respectively. Furthermore, oral administration in the infected chicken produced higher mean absorption time, delayed T_max, lower C_max, smaller AUC value and lower bioavailability (16.76). Based on these results, monitoring and adjustment of amoxicillin dosing could be practiced during the presence of coccidiosis. The measured C_max values suggest the administration of 1.3‐folds of the normal dose to maintain the normal maximal serum concentrations of amoxicillin in chicken infected with caecal coccidiosis.