Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses

Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (<1.010) and serum furosemide concentrations (>100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine the pharmacokinetic parameters of furosemide in equine serum samples and its effects on urinary SG after IV administration (250 mg) to 10 horses. Pharmacokinetic analysis showed that serum concentrations of furosemide were well described by a two-compartmental open model. Based on results in this study, it is very unlikely for horses to have serum furosemide concentrations greater than 100 ng/ml or urine SG less than 1.010 at 4 hours after administration (250 mg IV). However, it should be remembered that urine SG is a highly variable measurement in horses, and even without furosemide administration, some horses might naturally have urine SG values less than 1.010.     

Intradural vasculitis and hemorrhage in full sibling Welsh springer spaniels

Two, full sibling, Welsh springer spaniel presented at 8 and 18 mo of age with rapidly progressive ataxia, recumbency, and pyrexia. The spinal cord contained extensive subdural hemorrhage and, in 1 dog, suppurative and necrotizing arteritis in the dura. The findings suggest a familial form of canine juvenile polyarteritis syndrome.     

Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals

OBJECTIVE: To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. ANIMALS: 10 healthy foals. PROCEDURE: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. RESULTS: Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL RELEVANCE: Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.     

Effect of fenoldopam on renal function after nephrotomy in normal dogs

OBJECTIVE: To evaluate effects of fenoldopam on renal function in normal dogs subjected to bisection nephrotomy. In addition, effects of bisection nephrotomy on renal function in normal dogs were evaluated. STUDY DESIGN: Controlled, randomized, blinded experiment. SAMPLE POPULATION: Sixteen mixed-breed adult dogs. METHODS: Dogs were paired for sex, body weight, and approximate age and assigned to 1 of 2 groups: fenoldopam (F) or placebo (P). Baseline glomerular filtration rate (GFR) based on quantitative renal scintigraphy using (99m)Tc-DTPA, blood urea nitrogen (BUN), serum creatinine (SCr), urinalysis, and urine culture were performed before surgery. Left nephrotomy was performed via median celiotomy. Group F dogs were administered intravenous (IV) fenoldopam (0.1 microg/kg/min) for 90 minutes, whereas group P dogs were administered an equivalent volume of saline (0.9 % NaCl) solution for 90 minutes. Temperature, heart rate, respiration, direct arterial blood pressure, and urine volume were recorded during anesthesia. Renal function was assessed by measuring SCr, BUN, and GFR at 1, 21, and 42 days after surgery. RESULTS: There was no significant difference between groups in measured physiologic variables. No significant difference in GFR, BUN, or SCr between groups or between operated or control kidneys was detected. CONCLUSIONS: Bisection nephrotomy in normal dogs with renal arterial occlusion of 15 minutes and using a simple continuous capsular closure does not adversely affect renal function. CLINICAL RELEVANCE: Bisection nephrotomy, as described in this study, does not decrease renal function; perioperative administration of renoprotective agents is not necessary in normal dogs.     

Evaluation of a commercially available immunoassay for assessing adequacy of passive transfer in calves

OBJECTIVE: To evaluate diagnostic utility of a commercially available immunoassay for assessing adequacy of passive transfer of immunity in neonatal calves. DESIGN: Prospective study. ANIMALS: 123 calves. PROCEDURE: Blood and serum samples were obtained from the calves prior to 2 weeks of age. The immunoassay was performed, along with refractometry and an 18% sodium sulfite turbidity test. Serum IgG concentration was determined with a radial immunodiffusion assay. Sensitivity and specificity of the immunoassay, refractometry, and the sodium sulfite test were calculated by comparing results with results of the radial immunodiffusion assay. RESULTS: Sensitivity and specificity of the blood IgG immunoassay were 0.93 and 0.88, respectively, compared with 1.00 and 0.53 for the sodium sulfite test. For refractometry, sensitivity and specificity were 0.71 and 0.83, respectively, when a serum total solids concentration of 5.2 g/dl was used as the cutoff between positive and negative test results. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the immunoassay performs well in detecting calves with inadequate passive transfer of immunity.     

Comparison of hematologic and biochemical values for blood samples obtained via jugular venipuncture and via vascular access ports in cats

OBJECTIVE: To determine whether hematologic and serum biochemical values for blood samples obtained from cats via vascular access ports (VAP) are comparable to those for samples obtained by direct venipuncture. DESIGN: Prospective study. ANIMALS: 14 healthy cats. PROCEDURE: A VAP was surgically implanted in a jugular vein in each cat. Blood samples were obtained from the VAP and by direct venipuncture of the contralateral jugular vein 10 weeks after VAP placement. Results of hematologic and serum biochemical analyses were compared by use of a paired t-test. The Pvalue to reject the null hypothesis was adjusted to account for multiple comparisons by using the Bonferroni procedure in which the nominal P-to-reject value is divided by the number of comparisons (0.05/24 = 0.002). RESULTS: Paired samples (VAP and venipuncture) obtained 10 weeks after VAP placement were evaluated for each cat. Of the 24 measured analytes, only potassium, total protein, and albumin concentrations differed significantly (P< 0.001 for all 3) between VAP and venipuncture samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samples obtained from VAP are suitable for routine hematologic monitoring of feline cancer patients. Sample hemolysis may account for a slight increase in potassium, total protein, and albumin concentrations obtained from VAP samples. However, the values of variables most critical for monitoring of patients receiving chemotherapy (ie, mature neutrophil and platelet counts) are comparable. If proper techniques are used, VAP may be used for administration of chemotherapy as well as for blood collection in cats undergoing cancer treatment.