Early effects of ethylene glycol on the ultrastructure of the renal cortex in dogs

A sublethal dose of ethylene glycol was administered orally to 3 groups of dogs; dogs of a control group were given distilled water instead. Renal cortical biopsy samples were obtained from dogs of experimental and control groups at various times after treatment. Tissue was examined by use of light microscopy and transmission electron microscopy. In dogs of the control group, the light and electron microscopic appearances of tissue were within normal limits at all sample collection hours. In dogs of the experimental groups, renal corpuscular structure remained within normal limits by use of light and electron microscopy throughout the study, though morphologic change was seen in other structures of the cortex. Light microscopic lesions first appeared at 12 hours, and were similar to those reported in the literature. Ultrastructural lesions were first observed in the 5-hour samples, and similar to the light microscopic lesions, were most common in the proximal convoluted tubules (PCT). Initial PCT cellular changes included vacuolization of cells and distention of the parabasal extracellular spaces; PCT cellular lesions seen in later-hour samples included formation of apical buds and cellular rupture. Internalization or sloughing of the PCT brush border was not observed. Distal convoluted tubules (DCT) were frequently dilated and/or packed with cellular debris. A few DCT cells had degenerative or necrotic changes. In PCT and DCT, abnormal cells were frequently flanked by normal or nearly normal cells. During later hours, a few cells with types of changes first observed in early hours continued to be observed, implying ongoing response of cells to the toxin.     

Ultrasonographic findings in dogs and cats with oxalate nephrosis attributed to ethylene glycol intoxication: 15 cases (1984-1988)

Renal ultrasonographic findings in 12 dogs and 3 cats determined to have oxalate nephrosis presumed to be secondary to ethylene glycol intoxication were examined. Ultrasonographic changes varied from mild to marked increases in renal cortical echogenicity. A pattern of greater than normal cortical and medullary echogenicity with persistence of areas of lesser echo intensity at the corticomedullary junction and central medullary regions was observed. This pattern, termed the halo sign, was recognized in 7 dogs and 1 cat concurrent with the development of clinical anuria. Ultrasonographic patterns in these clinical cases were similar to those observed in a previous study of dogs with experimentally induced ethylene glycol nephrosis. Ultrasonographic findings were not considered pathognomonic of ethylene glycol nephrosis. Due to the high death rate reported in the cases surveyed, detection of ultrasonographic changes was considered to warrant a guarded to poor prognosis. Because of the association of the halo sign with anuria, its detection was considered to warrant a grave prognosis.     

Norepinephrine kinetics in dogs with experimentally induced renal vascular hypertension

OBJECTIVE: To determine norepinephrine (NE) kinetics in dogs with experimentally induced renal vascular hypertension. ANIMALS: 4 mixed-breed dogs. PROCEDURE: The study comprised a control and hypertensive period. The hypertensive period followed induction of renal vascular hypertension achieved by surgical placement of clips on both renal arteries to reduce diameter by approximately 80%. Arterial blood pressure, renal clearance, and NE kinetics were measured during each period while dogs were receiving a low-sodium diet. Measurements of NE kinetics and renal clearance during the hypertensive period were made 5 days after induction of hypertension. RESULTS: Five days after induction of hypertension, arterial blood pressure increased by 15 to 20 mm Hg. Mean (+/- SEM) plasma NE concentration and NE spillover rate increased significantly from 151.5+/-14.1 pg/ml and 8.03+/-0.62 ng/kg/min, respectively, during the control period to 631.4+/-30.5 pg/ml and 54.0+/-5.2 ng/kg/min, respectively, during the hypertensive period. Norepinephrine clearance rate also increased (54.0+/-2.4 vs. 86.0+/-9.3 ml/kg/min). Positive associations between mean arterial pressure (MAP) and NE concentration and spillover rate were detected. However, MAP and NE clearance rate were not associated. CONCLUSIONS AND CLINICAL RELEVANCE: Increased blood pressure during the hypertensive period was likely attributable to increased NE spillover rate, which resulted in a significant increase in plasma NE concentration. Analysis of these results suggests that central sympathetic outflow was increased and may be responsible for the pathogenesis of high blood pressure during the acute phase of renal vascular hypertension in dogs.     

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.     

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.     

Taste responses of dogs to ethylene glycol, propylene glycol, and ethylene glycol-based antifreeze

Although it is widely believed that ethylene glycol-based antifreeze (AF) is an attractive tastant to dogs and other animals, empirical data on this point are not available. In experiment 1, we examined the propensity of 178 adult mixed-breed dogs to approach, sniff, and lick a concentration of AF commonly used in automotive cooling systems (50%). Despite the fact that most of the dogs approached and sniffed the AF in these 5-minute tests, only 9% initiated lick responses and most of these were brief and not followed by additional licking. In experiment 2, the lick responses of five gastric-cannulated dogs to aqueous solutions of 20% sucrose, 50% ethylene glycol, 50% propylene glycol, water, and 50% AF were examined in 14-minute tests before and after periods of food and water deprivation. Under the latter conditions, 2 of the 5 dogs drank amounts of ethylene glycol that would have been lethal to uncannulated dogs. None of the five dogs drank potentially lethal amounts of AF. The preference order for these tastants was sucrose greater than water greater than ethylene glycol greater than AF = propylene glycol. Although these findings question the general belief that AF is highly palatable to most dogs, they do imply that large individual differences in responsiveness exist and that AF ingestion is likely influenced by motivational state. Furthermore, they suggest the possibility that unpleasant-tasting additives could be successfully developed to eliminate the ingestion of AF, because the initial attractiveness of AF is relatively low. Such additives would have to be stable in vehicular cooling systems and not adversely affect the functional aspects of AF performance.     

1,3 Butanediol treatment of ethylene glycol toxicosis in dogs

In order to assess the therapeutic value of 1,3 butanediol in ethylene glycol toxicosis, mixed-bred dogs were given an oral dose of commercial antifreeze at 6 ml/kg of body weight (0 hour) and treated (IV) 7 times at 6-hour intervals with 5.5 ml/kg of body weight 1,3 butanediol solution (20% in physiological saline solution) beginning at 8, 12, and 21 hours. Serum glycolic acid concentration was quantitated by high-pressure liquid chromatography. Three dogs that were given ethylene glycol, but no 1,3 butanediol treatment, died with elevated serum glycolic acid concentrations. Five dogs were given ethylene glycol and 1,3 butanediol treatment. Of 2 dogs treated at 8 hours, 1 survived and 1 died at 39 hours; 1 treated at 12 hours and 1 treated at 21 hours survived; 1 dog died soon (27 hours) after treatment was initiated at 21 hours. Four of the 5 dogs had dramatically decreased serum glycolic acid concentrations after 1,3 butanediol treatment, indicating its effectiveness in inhibiting alcohol dehydrogenase-dependent glycolic acid formation in vivo.     

Hyperosmolemic changes following experimental ethylene glycol intoxication in dogs

Experimental ethylene glycol toxicosis in dogs produced a marked increase in serum osmolality. By comparing measured and calculated serum osmolality and relating this difference to plasma ethylene glycol, it was determined that ethylene glycol was primarily responsible for the hyperosmolemia. Osmometry may provide a useful adjunct to other diagnostic tests in identifying ethylene glycol intoxicated dogs during the early, most treatable, stage of toxicosis.     

Ochratoxin A and citrinin induced nephrosis in Beagle dogs. III. Terminal renal ultrastructural alterations

The extent and type of renal ultrastructural changes in Beagle dogs varied with the administration of ochratoxin A and citrinin alone and in the two dosage combinations. The three predominant changes were cytoplasmic vacuolation, myelin figure formation and lesions designated as cytoplasmic disarray. These changes were mainly of the endomembane system of the tubular epithelial cells. Cytoplasmic vacuoles were within proximal and distal tubules and collecting ducts and were most numerous in dogs given 10 mg/kg critrinin. Vacuolation of similar distribution, but less severe, was seen in renal tubular cells of dogs given the higher dose of the combined mycotoxins (0.2 mg/kg ochratoxin A + 10 mg/kg citrinin). This damage was limited to the proximal tubular cells in dogs given only ochratoxin A (0.1 or 0.2 mg/kg). Myelin figures were in proximal epithelial cells of dogs given ochratoxin A alone or combined with citrinin. There was cytoplasmic disarray in dogs of all groups except for dogs given 5 mg/kg citrinin. This lesions was usually limited to the proximal tubules. The lesions, however, was found in cells of the distal tubules of dogs given 10 mg/kg citrinin alone.     

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.     

Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome

The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty‐seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.     

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.