Early renal ultrasonographic findings in dogs with experimentally induced ethylene glycol nephrosis

Renal ultrasonographic changes were evaluated in 5 dogs administered 10 ml of commercial antifreeze (95% ethylene glycol)/kg of body weight, PO, and in 2 dogs given placebos. Studies were made prior to and after ingestion on an hourly basis over a period of 8 to 10 hours. All dogs were anesthetized immediately after toxin or placebo ingestion for the duration of the study. Renal cortical echogenicity was evaluated in comparison with that of the adjacent liver and spleen. Echogenicity of the renal medulla and definition of the corticomedullary junction were assessed. Within 4 hours after ethylene glycol administration, renal cortical echogenicity of all intoxicated dogs increased from normal to surpass that of liver and approach or equal that of the spleen. Medullary echogenicity in all intoxicated dogs progressively increased over the course of the study, with changes recognized within 5 hours after ethylene glycol administration. An ultrasonographic pattern consisting of nearly equal, marked increase in cortical and medullary echogenicity and relatively hypoechoic corticomedullary junction and central medullary regions was recognized concurrent with the development of anuria in 3 of the 5 intoxicated dogs. Mild, transient increases in cortical and medullary echogenicity were observed in anesthetized control dogs. However, no statistical difference (P less than 0.05) was detected between baseline, peak, and terminal echogenicity values in these dogs. Blood and urine samples were collected hourly from intoxicated dogs to coincide with ultrasonographic studies. Most clinicopathologic values derived from these samples were not statistically different (P less than 0.05) from those reported in a study that used a similar intoxication protocol in nonanesthetized dogs.     

Association of systemic hypertension with renal injury in dogs with induced renal failure

Systemic hypertension is hypothesized to cause renal injury to dogs. This study was performed on dogs with surgically induced renal failure to determine whether hypertension was associated with altered renal function or morphology. Mean arterial pressure (MAP), heart rate (HR), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) were measured before and after surgery. Glomerular filtration rate (GFR) and urine protein:creatinine ratios (UPC) were measured at 1, 12, 24, 36, and 56-69 weeks after surgery, and renal histology was evaluated terminally. The mean of weekly MAP, SAP, and DAP measurements for each dog over the 1st 26 weeks was used to rank dogs on the basis of MAP, SAP, or DAP values. A statistically significant association was found between systemic arterial pressure ranking and ranked measures of adverse renal responses. When dogs were divided into higher pressure and lower pressure groups on the basis of SAP, group 1 (higher pressure, n = 9) compared with group 2 (lower pressure, n = 10) had significantly lower GFR values at 36 and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, and fibrosis. When dogs were divided on MAP and DAP values, group 1 compared with group 2 had significantly lower GFR values at 12, 24, 36, and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, fibrosis, and cell infiltrate. These results demonstrate an association between increased systemic arterial pressure and renal injury. Results from this study might apply to dogs with some types of naturally occurring renal failure.     

Characterization of the renal response to protein ingestion in dogs with experimentally induced renal failure.

Effects of a protein meal (2.7 g of casein/kg of body weight) on glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed in dogs after 15/16 nephrectomy (n = 10), and were compared with observations in dogs with intact kidneys (n = 5). Increase in GFR and RPF was observed in both groups of dogs between 1.5 and 8 hours after protein ingestion. A maximal value for GFR was observed between 4 and 5 hours after protein ingestion in dogs of both groups. Enhancement of urinary protein excretion was evident in partially nephrectomized dogs after protein ingestion (P less than 0.05), a result that was confirmed by 24-hour total urine collection from partially nephrectomized dogs fed a balanced ration. A qualitatively similar vasodilatory response was observed in partially nephrectomized dogs and in dogs with intact kidneys, and the mean maximal increase of GFR and RPF expressed as a percentage of baseline values in the latter dogs (47.0 +/- 8.1 and 43.6 +/- 10.3%, respectively) exceeded that observed in partially nephrectomized dogs (20.8 +/- 2.2 and 22.7 +/- 6.3%, respectively; P less than 0.01). The incremental response of the kidneys to protein ingestion was directly related to the degree of renal function, as reflected in the linear regression relationship between the incremental increase in GFR and the baseline value for GFR (P less than 0.01, R2 = 0.721).     

Investigation of renal protein loss in dogs with acute experimentally induced Ehrlichia canis infection.

Urinary protein-to-creatinine ratios and serum albumin concentrations were measured in 8 adult male dogs experimentally inoculated with Ehrlichia canis. Urinary protein concentration increased significantly, but transiently, during the acute phase of infection. Urinary protein-to-creatinine ratios were highest (mean, 8.6) during the third and fourth weeks after infection, and decreased to less than 0.5 by 6 weeks after infection. Correspondingly, albumin concentration decreased significantly during the acute phase. Serum albumin concentrations were lowest (mean, 2.1 g/dl) the fourth week after infection and increased to greater than 3.0 g/dl by 11 weeks after infection. There was an inverse linear correlation between urinary protein-to-creatinine ratio and serum albumin concentration. The magnitude of proteinuria and its inverse relationship with serum albumin concentration suggested that hypoalbuminemia associated with acute E canis infection may be attributable primarily to increased renal loss of protein, rather than decreased hepatic synthesis as previously suggested. Another dog was subsequently inoculated with E canis from 1 of the experimentally infected dogs and a renal biopsy was performed during peak proteinuria (urinary protein-to-creatinine ratio = 22 and serum albumin = 1.1 g/dl). Immunofluorescent staining revealed mild to moderate deposits of anti-canine IgM, and to a lesser extent, anti-canine IgG and complement factor C3 in the glomerular tufts and mesangium. Ultrastructural evaluation revealed distortion and fusion of podocyte foot processes and increased microvilli on podocytes. These morphologic changes were consistent with transient glomerular leakage of protein of a magnitude that would significantly contribute to hypoalbuminemia during acute E canis infection. An underlying immunologic mechanism was suggested by positive glomerular immunofluorescence and previously described histologic findings.     

Serum bile acid analysis in dogs with experimentally induced cholestatic jaundice

Serum bile acid (SBA) concentration was determined weekly for 4 weeks in dogs with experimentally induced hyperbilirubinemic liver disease. Obstructive jaundice was created in 6 dogs by surgical ligation of the common bile duct, and hepatocellular jaundice was created in 6 sham-operated dogs by administration of dimethylnitrosamine; 6 other sham-operated dogs served as controls. Serum bile acid concentration increased rapidly after bile duct ligation (from 0.6 +/- 0.1 to 69.2 +/- 15.3 mumol/L at 3 days), peaked at 14 days (247.8 +/- 54.1 mumol/L), and then gradually decreased (179.9 +/- 27.1 mumol/L at 28 days). Serum bile acid concentration in dimethylnitrosamine-treated dogs increased more gradually to 38.9 +/- 10.7 mumol/L at 28 days, at which time the serum bilirubin concentration was comparable with that of bile duct-ligated dogs. Mean total SBA values in bile duct-ligated dogs were significantly (P less than 0.01) higher than those in control and dimethylnitrosamine-treated dogs at days 3 through 28, with no overlap of individual values. Serum bile acid concentration at day 28 correlated positively (P less than 0.01) with cholestasis and bile duct proliferation observed in liver biopsy specimens, but did not correlate with necrosis or inflammation. Serum bile acid concentration also correlated positively (P less than 0.01) with serum bilirubin and cholesterol concentrations and with serum alkaline phosphatase and alanine transaminase activities. Results of the study reported here indicated a relationship between SBA concentration and cholestasis in dogs; extrahepatic bile duct obstruction resulted in the highest SBA values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of urinary tract infection in dogs with experimentally induced hyperadrenocorticism

Objectives of this study were to determine occurrence of urinary tract infection and describe results of urine analysis and urine culture in dogs with experimentally induced hyperadrenocorticism. Dogs were randomly assigned to receive either hydrocortisone (nine dogs) or placebo (eight dogs) for 49 consecutive days. Before and on day 49 of treatment, evaluation of dogs included physical examination, abdominal ultrasound, urine culture, urinalysis, adrenal function testing, and measurement of urine protein and creatinine and activity of serum alkaline phosphatase. All dogs in the experimental group had clinical and laboratory findings of hyperadrenocorticism. Urine specific gravity was significantly decreased and urine protein-to-creatinine ratio was significantly increased in dogs with hyperadrenocorticism. Urinary tract infection did not occur in any dogs. We conclude that administration of hydrocortisone created a model of hyperadrenocorticism; however, urinary tract infection did not occur. Additional evaluation is needed to determine association between urinary tract infection and hyperadrenocorticism.     

Increased renal vascular resistance in dogs with hepatic disease

Doppler ultrasound is a non-invasive technique that can be used to estimate vascular resistance by calculation of resistive index (RI) and pulsatility index (PI). Liver disease may increase renal RI and PI, and in humans with liver disease the indices are monitored to attain prognostic information. Systemic hypertension has been found in dogs with hepatic disease and is also related to increased renal vascular resistance in humans. The aim of this study was to examine renal vascular resistance increases in dogs with hepatic disease and to ascertain whether these may be related to blood pressure increases and biochemical parameters. Twenty dogs with hepatic disease were evaluated. The mean renal RI, PI, and systolic blood pressure were significantly higher than in normal animals. A positive correlation was found between the indices and alkaline phosphatase but not with systolic blood pressure. It is concluded that renal vascular resistance may increase in dogs with hepatic disease and in this study was above the limit value in 50% of the animals.     

Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus.

In dogs, gastric dilatation-volvulus (GDV) is characterized by cardiogenic shock, with resulting hypoperfusion. Treatment goals include reperfusion of transiently ischemic tissues, which indicates that reperfusion injury may be a factor in the physiopathogenesis of GDV. Recently, we obtained data that indicate that reperfusion injury may be involved in experimentally induced GDV. Using this GDV model, we evaluated mortality in 24 dogs of 4 equal groups, treated with deferoxamine (an iron chelator), dimethylsulfoxide (a free radical scavenger), a combination of the 2 drugs, or isotonic saline solution. All 6 dogs that were given deferoxamine survived; however, 3 dogs of the dimethylsulfoxide-treated group, 2 dogs of the combination-treated group, and 4 dogs of the saline-treated group died. Results of the study indicate that mortality associated with experimentally induced GDV is reduced by appropriate and timely pharmacologic intervention to prevent or attenuate reperfusion injury, and that deferoxamine may be more effective than dimethylsulfoxide.     

Serum antiprotease concentrations in dogs with spontaneous and experimentally induced acute pancreatitis

A significant decline (P = 0.047) in serum antiprotease concentration was detected in dogs with experimentally induced acute pancreatitis. Decreased serum antiprotease concentrations, similar in magnitude to those documented in the experimental dogs, were present in dogs with spontaneous, acute pancreatitis. These findings suggest that significant amounts of proteolytic enzymes escape into the systemic circulation during acute pancreatitis in dogs. These circulating enzymes may be involved in the extrapancreatic complications of acute pancreatitis.     

Acute phase protein response in dogs with experimentally induced gastric mucosal injury

Background: The acute phase response is part of the innate defense system of an animal against trauma, inflammation, and infection. Objective: The purpose of this investigation was to evaluate the acute phase response in dogs with acetylsalicylic acid-induced gastric mucosal injuries and to determine its potential diagnostic significance. Methods: Ten, healthy, cross-breed dogs (6 females and 4 males) were given oral acetylsalicylic acid in a single oral dose of 200 mg/kg for the experimental model of acute gastric mucosal injury. Heparinized blood samples were collected before (day 0) and on days 1, 4, and 7 after acetylsalicylic acid administration to determine plasma C-reactive protein (CRP), serum amyloid-A (SAA), haptoglobin, fibrinogen, total protein, albumin, and iron concentrations. Total WBC counts were done in whole blood. Endoscopy was done on each of the selected days, and gastric lesions were scored and localized. Results: Hemorrhagic linear erosions were found in all dogs on day 1, concurrent with significant increases in CRP, SAA, haptoglobin, and fibrinogen concentrations, and in WBC counts; however, iron concentration was decreased. Peak haptoglobin and fibrinogen concentrations occurred on day 4, at which time only nonhemorrhagic lesions were observed endoscopically. On day 7, results for all analytes except haptoglobin had returned to baseline levels, along with resolution of most gastric lesions. Conclusions: Results of this study indicate that a rapid acute phase protein response occurs after induced gastric mucosal injury in dogs and may be potentially useful together with gastroscopy in the diagnosis and monitoring of gastric injury.     

Liver biochemical and histopathological findings in dogs with experimentally induced exocrine pancreatic insufficiency

Routine liver biochemical parameters were evaluated in 8 dogs with exocrine pancreatic insufficiency (EPI) induced by surgical ligation of the pancreatic duct and the pancreatic branch of the pancreaticoduodenal artery and confirmed with the trypsin-like immunoreactivity test. Eight additional dogs were used as healthy controls. Data collection began at the 4th week postoperatively and continued weekly to the 21st week. In the dogs with EPI, the serum activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were consistently elevated. The serum total and conjugated bilirubin concentrations remained within normal limits throughout the experimental period. Histopathological study revealed hepatic lipidosis in the dogs with EPI. Therefore, since this condition seems to be an additional consequence of EPI in dogs, laboratory evaluation of dogs with EPI must include assessment of liver function, to determine if additional or different therapeutic measures are indicated.     

Hyponatremia and hyperkalemia associated with idiopathic or experimentally induced chylothorax in four dogs

Two dogs with idiopathic chylothorax and 2 dogs with experimentally induced (ie, ligation of the cranial vena cava) chylothorax were treated by intermittent thoracic drainage. Of these 4 dogs, 3 that did not have evidence of renal failure had normal or near-normal serum sodium and potassium concentrations before thoracic drainage began, and all 3 developed repeatedly marked hyponatremia and hyperkalemia during thoracic drainage. Another dog became weak and depressed, ostensibly because of hyperkalemia. Serum sodium and potassium concentrations in 1 dog with spontaneous chylothorax returned to normal after chylothorax resolved and thoracic drainage was stopped. The other 3 dogs died or were euthanatized, and the effect of stopping thoracic drainage could not be evaluated. In 3 dogs in which it was measured, normal-to-high plasma cortisol concentration was observed before and after adrenocorticotropin administration, and 2 dogs also had hyperaldosteronemia. Hyponatremia was hypothesized to be caused by sodium loss via thoracic drainage whereas hyperkalemia may have been multifactorial in origin, but probably was attributable, at least, in part to decreased renal potassium clearance.     

Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity

OBJECTIVE: To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. ANIMALS: 12 na?ve Beagle pups (9 sensitized and 3 control dogs). PROCEDURE: 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. RESULTS: High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. CONCLUSIONS AND CLINICAL RELEVANCE: Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.     

Effects of flunixin meglumine in dogs following experimentally induced endotoxemia

Twelve dogs were randomly divided into three groups. Group 1 dogs were given Escherichia coli endotoxin and then treated with flunixin meglumine. Group 2 dogs were given endotoxin as group 1, but untreated. Group 3 dogs were given flunixin meglumine alone. The dogs were monitored clinically and urine and serum samples were collected at regular intervals for 72 hours. All surviving dogs were humanely killed after 72 hours and examined for gross and histologic lesions. Group 1 dogs all survived 72 hours, but showed prerenal azotemia, hepatocellular damage, hemorrhagic enteritis, and numerous gastric ulcerations. Three of the four dogs in group 2 died before 72 hours. Group 2 dogs showed many of the same chemical and hemodynamic changes as group 1. They had severe hemorrhage into the intestinal lumen; however, there were no gastric ulcerations. Group 3 dogs all survived and showed little physical or hematologic change. The study suggested the following: 1) flunixin meglumine was an effective drug in ameliorating the fatal effects of canine endotoxemia, 2) the effects of endotoxin in combination with flunixin meglumine, at 1.1 mg/kg body weight, caused gastric ulcerations, and 3) in normal dogs flunixin meglumine at 1.1 mg/kg body weight did not cause severe side effects or gross lesions.     

Effects of milbemycin on adult Toxocara canis in dogs with experimentally induced infection

To determine the efficacy of a formulation of milbemycins in treating patent infection with Toxocara canis, 8 male and 7 female, 10-week-old, ascarid-free Beagles each were given 125 embryonated eggs of T canis. All dogs developed patent infection within 56 days. On post-infection day 70, the dogs were assigned to 1 of 3 groups of 5 dogs each; members of 1 group were given a placebo, while dogs of the other 2 groups were given either 5.68 or 34.08 mg of the milbemycin formulation, respectively. In both groups of dogs given the drug, the number of eggs passed per gram of feces decreased precipitously. However, a few eggs still were found in the feces of several dogs of each group on the day of necropsy (postinfection day 75). Worms or fragments of worms were passed by the treated dogs from the day of treatment until the day on which necropsy was performed; however, most worms were passed during the first 2 days after treatment. At necropsy, only dogs of the control group were found to harbor adult T canis.     

Serum pancreatic polypeptide and amylase concentrations in dogs with experimentally induced acute pancreatitis

Serum concentrations of immunoreactive pancreatic polypeptide (IPP) were measured serially for 7 days after experimental induction of acute hemorrhagic pancreatitis in dogs by infusion of oleic acid into the pancreatic duct. The mean serum IPP concentrations in dogs with pancreatitis were increased significantly (P = 0.013) for 96 hours after induction of pancreatitis. Providing food at 108 hours resulted in significant increases (P = 0.032) in mean serum IPP concentrations in sham-operated control dogs compared with dogs with induced pancreatitis. This was attributed to cephalic-phase release of IPP due to a conditioned response that resulted from feeding immediately after each blood sampling. Mean serum IPP concentrations returned to base line more quickly than did mean serum amylase concentrations in dogs with pancreatitis.