Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors.

OBJECTIVE: To determine clinical status and renal and hematopoietic function after kidney donation and identify risks associated with kidney donation in dogs. DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined prospectively at various times after nephrectomy, and pre- and postnephrectomy CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine creatinine ratio were compared. Six dogs had postnephrectomy renal volume determined ultrasonographically, and 4 of those dogs also underwent scintigraphic determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs were clinically normal at the time of reevaluation. There were no significant differences between prenephrectomy and postnephrectomy values for BUN concentration or urine specific gravity. Mean postnephrectomy serum creatinine concentration was significantly greater than prenephrectomy concentration. Mean serum phosphorus concentration was significantly decreased after nephrectomy, and mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were significantly increased after nephrectomy. Postnephrectomy renal volume was greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51 mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and hematopoietic variables were within reference ranges in dogs examined up to 2.5 years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest in dogs < 1 year of age at donation. Donor age, along with histocompatability, may be an important factor in selecting dogs for kidney donation.

Effect of heartworm disease and heartworm-associated respiratory disease (HARD) on the right ventricle of cats.

BACKGROUND: Dirofilaria immitis infection occurs in dogs and cats, both of which species are clinically affected by mature adult infections. Cats are uniquely affected by immature-adult infections with an inflammatory pulmonary disease called Heartworm-Associated Respiratory Disease (HARD). D. immitis infection causes pulmonary parenchymal and vascular pathology in the dog and cat. Dogs develop pulmonary hypertension and cor pulmonale, whereas the development of pulmonary hypertension is rare in the cat. D. immitis infection in the dog causes alteration of the right ventricular (RV) extracellular matrix, including a decrease in myocardial collagen. In this study, the RV myocardial changes of cats infected with adult and immature-adult D. immitis were assessed. METHODS: The cardiopulmonary systems of six groups of SPF cats (n = 9-10 per group) were examined 8 or 18 months after infection with L3 D. immitis. Two groups were untreated and allowed to develop adult HW; two groups were treated with ivermectin starting 3 months post infection, thus allowing HARD but no mature adult heartworms; and two groups were treated with selamectin beginning 1 month post infection, preventing development of L5 or adult heartworms. A group of specific pathogen free (SPF) normal cats was utilized as a negative control (n = 12). Lung pathologic lesions were objectively assessed, and both RV and left ventricular (LV) weights were obtained to calculate an RV/LV ratio. Intramural RV myocardial collagen content was quantitatively assessed. RESULTS: RV/LV weight ratios were not different between groups. Negative control cats had significantly greater RV collagen content than all other affected groups (P = 0.032). Analysis of the RV/LV ratios and collagen content revealed no significant relationship (r = 0.03, P = 0.723, respectively). Collagen content had a modest, but significant, negative correlation, however, with both pulmonary vascular pathology (r = -0.25, P = 0.032) as well as the total pulmonary parenchymal and vascular pathology (r = -0.26, P = 0.025). CONCLUSIONS: Cats infected with mature and immature D. immitis did not develop RV hypertrophy but did demonstrate loss of RV myocardial collagen content. The collagen loss was present at 8 and 18 months after infection in all infected cats. This loss of RV myocardial collagen was correlated with the severity of pulmonary parenchymal and vascular pathology.

Influence of dietary calcium and phosphorus content in a fixed ratio on growth and development in Great Danes.

OBJECTIVE: To study the musculoskeletal development of Great Dane puppies fed various dietary concentrations of calcium (Ca) and phosphorus (P) in fixed ratio by use of dual energy x-ray absorptiometry (DEXA), determination of serum insulin-like growth factor 1 and parathyroid hormone concentrations, radiography, and blood chemistry analysis results. ANIMALS: 32 purebred Great Dane puppies from 4 litters. PROCEDURE: At weaning, puppies were assigned randomly to 1 of 3 diets. Blood was collected for biochemical analyses and hormone assays, and radiography and DEXA were performed through 18 months of age. Changes in body weight, bone mineral content, fat tissue weight, lean mass, result of serum biochemical analyses, hormonal concentrations, and radius lengths were analyzed through 18 months of age. RESULTS: Bone mineral content of puppies correlated positively with Ca and P content of the diets fed. Significant differences between groups in bone mineral content, lean mass, and body fat were apparent early. The disparity among groups increased until 6 months of age and then declined until body composition was no longer different at 12 months of age. Accretion rates for skeletal mineral content, fat, and lean tissue differed from each other and by diet group. CONCLUSIONS AND CLINICAL RELEVANCE: Ca and P concentrations in the diet of young Great Dane puppies are rapidly reflected in the bone mineral content of the puppies until 5 to 6 months of age, after which hormonal regulation adjusts absorption and excretion of these minerals. Appropriate Ca and P concentrations in diets are important in young puppies < 6 months of age.

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Magnetic resonance imaging of radiation-induced thymic atrophy as a model for pathologic changes in acute feline immunodeficiency virus infection.

The development of a protocol to reproducibly induce thymic atrophy, as occurs in feline immunodeficiency virus (FIV) infection and other immunosuppressive diseases, and to consistently estimate thymic volume, provides a valuable tool in the search of innovative and novel therapeutic strategies. Magnetic resonance imaging (MRI) using the short tau inversion recovery (STIR) technique, with fat suppression properties, was determined to provide an optimized means of locating, defining, and quantitatively estimating thymus volume in young cats. Thymic atrophy was induced in four, 8-10-week-old kittens with a single, directed 500 cGy dose of 6 MV X-rays from a clinical linear accelerator, and sequential MR images of the cranial mediastinum were collected at 2, 7, 14, and 21 days post irradiation (PI). Irradiation induced a severe reduction in thymic volume, which was decreased, on average, to 47% that of normal, by 7 days PI. Histopathology confirmed marked, diffuse thymic atrophy, characterized by reduced thymic volume, decreased overall cellularity, increased apoptosis, histiocytosis, and reduced distinction of the corticomedullary junction, comparable to that seen in acute FIV infection. Beginning on day 7 PI, thymic volumes rebounded slightly and continued to increase over the following 14 days, regaining 3-35% of original volume. These findings demonstrate the feasibility and advantages of using this non-invasive, in vivo imaging technique to measure and evaluate changes in thymic volume in physiologic and experimental situations. All experimental protocols in this study were approved by the Institutional Animal Care and Use Committee (IACUC) at Auburn University.

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation.

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.