A longitudinal study of the persistence of increased creatinine and concordance between kidney biomarkers in cats and dogs.

Kidney disease causes morbidity and mortality in dogs and cats. Serum creatinine concentration is an important surrogate marker for glomerular filtration rate (GFR). However, it is not always sensitive to small decreases in kidney function. Efforts to identify additional, more sensitive surrogate markers of GFR to improve detection of early kidney disease has led to the use of symmetrical dimethylarginine (SDMA) in veterinary medicine. There is insufficient information about the behavior of creatinine after an increase and the expected behavior of creatinine and SDMA in these cats and dogs. This study assesses the probability of persistence of increases in creatinine and the subsequent behavior of creatinine and SDMA in animals with persistently increased creatinine. For enrollment, three paired SDMA and creatinine concentrations were required: baseline (T0) with creatinine and SDMA at or below the upper reference limit (URL), T1, and T2 0.5-18 months after T1. The study included 4517 cats and 4576 dogs with increased T1 creatinine concentrations and 54,295 cats and 125,403 dogs with T1 creatinine at or below the URL. The probability of a persistently increased creatinine at T2 was approximately 58% for cats and 49% for dogs after a T1 increase. For animals without a T1 increase the probability of increased creatinine at T2 was only 7% for cats and 3% for dogs. For cats and dogs with persistently increased Cr, the probability of an increased SDMA concentration at T1 was 70-75%. By 24 months, that probability rose to 94% for cats and 88% for dogs.

Longitudinal evaluation of symmetric dimethylarginine and concordance of kidney biomarkers in cats and dogs.

Symmetric dimethylarginine (SDMA) is a sensitive surrogate marker for glomerular filtration rate; however, there are uncertainties as to how to interpret mild increases (SDMA 15-19 µg/dL). This descriptive study used retrospective data to evaluate whether cats or dogs that had initial SDMA values (at T0) within the reference interval followed by an increased SDMA (at T1) had persistently increased SDMA (at T2; measured from 14 days to 18 months following T1; Persistence Cohort), and if and when cats or dogs with persistently increased SDMA had increased creatinine up to 24 months (Concordance Cohort). The Persistence Cohort included 16,670 cats and 16,712 dogs. If SDMA at T1 was 15-19 µg/dL, the probability of persistence was 53% for cats and 42% for dogs, while creatinine was concurrently increased in 20% of cats and 18% of dogs. For comparison, if SDMA was not increased at T1 the probability of increased SDMA at recheck was only 20% for cats and 9% for dogs. For cats and dogs with a T1 SDMA of 15-19 µg/dL and with persistent increases at T2, the probability of increased creatinine at T1 was 20% for cats and 18% for dogs, rising to 61% and 55%, respectively, by 24 months. When SDMA at T1 was >25 µg/dL, creatinine was increased in 93% of cats and 92% of dogs by 24 months. Mildly increased SDMA results may provide an opportunity to identify some cats and dogs earlier in their kidney disease.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES: There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS: Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS: Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION: The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.

The Effect of Chinese rhubarb, Rheum officinale, with and without benazepril on the progression of naturally occurring chronic kidney disease in cats.

BACKGROUND: Renal fibrosis is common in progressive kidney disease. Transforming growth factors ß (TGF-ß) are important mediators of all types of fibrosis, including renal fibrosis. Chinese rhubarb has been shown to have antifibrotic properties in part because of inhibition of TGF-ß and has slowed the progression of kidney disease in rodent models. HYPOTHESIS: That administration of a Chinese rhubarb supplement will slow the progression of chronic kidney disease (CKD) in cats and the concurrent administration of Chinese rhubarb and benazepril will be more effective than either alone. ANIMALS: Twenty-nine client-owned cats with naturally occurring IRIS Stage 2 or early Stage 3 CKD and without comorbidity such as cancer, urinary tract obstruction, urinary tract infection, poorly controlled hyperthyroidism, or systemic hypertension were enrolled in the study. METHODS: A randomized, positive-controlled, prospective study was performed. Cats received Chinese rhubarb, benazepril, or both in addition to standard treatment for CKD. Repeated measures ANOVA was used to assess changes in serum creatinine concentration, body weight, hematocrit, urine protein: urine creatinine ratio (UPC), and systemic arterial blood pressure over time between and within treatment groups over an average of 22 months. RESULTS: No significant differences were detected in serum creatinine concentration, body weight, hematocrit, UPC, and systemic arterial pressure over time between or within treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: This study failed to detect a significant difference in the progression of CKD in cats treated with Chinese rhubarb, benazepril, or both. Further study in specific subsets of cats with CKD is warranted.

Consensus recommendations for the diagnostic investigation of dogs with suspected glomerular disease.

BACKGROUND: The International Renal Interest Society (IRIS) offers guidelines for chronic kidney disease and acute kidney injury. As dogs with glomerular disease may present differently and require different treatment than those with whole nephron or tubular disease, the IRIS Canine Glomerulonephritis (GN) Study Group was convened to formulate guidelines for these cases. The Diagnosis Subgroup was asked to make recommendations for diagnostic evaluation of such cases. OBJECTIVE: To seek consensus among renal specialists for the evaluation of dogs with proteinuria because of suspected glomerular disease. METHODS: After reviewing the literature, subgroup members discussed and wrote the draft paper and recommendations, which members of the IRIS Canine GN Study Group voted upon by electronic secret ballot, with comments noted. Consensus was declared if votes showed strong or general agreement from 85% of the respondents. RESULTS: Diagnostic tests were categorized as essential, recommended, or potentially helpful, with prioritization dependent on case characteristics, eg, for cases with uncomplicated proteinuria versus complicated with hypoalbuminemia, azotemia, or both. Consensus was reached with 86-100% agreement on all questions posed. All cases should have basic examinations including blood pressure measurement, blood, and urine testing, and a search for infectious diseases relevant to their environs. The majority ranked imaging (chest radiographs, abdominal ultrasonogram) and renal biopsy procured and interpreted by experienced personnel as essential evaluations in complicated cases, but a few respondents deemed these to be essential in uncomplicated cases as well. CONCLUSIONS AND CLINICAL IMPORTANCE: Strong consensus about recommendations for diagnostic evaluation of dogs with suspected glomerular protein loss was attained. These guidelines help clinicians characterize disease processes for more informed therapeutic decision-making.

Comparison of signalment, clinicopathologic findings, histologic diagnosis, and prognosis in dogs with glomerular disease with or without nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) develops most commonly in people with glomerular diseases associated with marked albuminuria. Hypernatremia, hypertension, and progressive renal failure are more prevalent in nephrotic than nonnephrotic human patients. HYPOTHESIS/OBJECTIVES: Dogs with NS have higher serum cholesterol, triglyceride, and sodium concentrations, higher urine protein:creatinine ratios (UPC) and systolic blood pressure, and lower serum albumin concentrations than dogs with nonnephrotic glomerular disease (NNGD). NS is associated with membranous glomerulopathy and amyloidosis. Affected dogs are more likely to be azotemic and have shorter survival times. ANIMALS: Two hundred and thirty-four pet dogs (78 NS dogs, 156 NNGD dogs). METHODS: Multicenter retrospective case-control study comparing time-matched NS and NNGD dogs. NS was defined as the concurrent presence of hypoalbuminemia, hypercholesterolemia, proteinuria, and extravascular fluid accumulation. Signalment, clinicopathologic variables, histopathologic diagnoses, and survival time were compared between groups. RESULTS: Age, serum albumin, chloride, calcium, phosphate, creatinine, and cholesterol concentrations, and UPC differed significantly between NS and NNGD dogs. Both groups were equally likely to be azotemic at time of diagnosis, and NS was not associated with histologic diagnosis. Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (< or ≥1.5 mg/dL), survival of NS versus NNGD dogs was only significantly different in nonazotemic dogs (51 versus 605 days, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Presence of NS is associated with poorer prognosis in dogs with nonazotemic glomerular disease. Preventing development of NS is warranted; however, specific interventions were not evaluated in this study.

Canine glomerulonephritis: new thoughts on proteinuria and treatment.

Glomerular disease in the dog is not only a common form of renal disease but also an important cause of chronic renal failure. The presence of immune complexes in glomerular capillary walls is a major cause of canine glomerular disease and is commonly referred to as glomerulonephritis. Leakage of plasma proteins, principally albumin, across the damaged glomerular capillary walls results in persistent proteinuria--the clinicopathological hallmark of glomerulonephritis. Recent evidence suggests that, in addition to being a marker of disease, persistent proteinuria is associated with progressive glomerular and tubulointerstitial lesions and loss of additional nephrons. Perhaps the best treatment for glomerulonephritis is the identification and correction of any underlying inflammatory, immune-mediated or neoplastic disease that results in the deposition or formation of glomerular immune complexes. In cases of idiopathic glomerulonephritis, angiotensin-converting enzyme inhibitors have been shown to decrease proteinuria and potentially slow disease progression.

Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis.

A blinded, multicenter, prospective clinical trial assessed the effects of enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months (1 dog was treated first with the placebo and then with EN). All dogs were treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet. At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and glomerular histologic grade were not different between groups, but the urine protein/creatinine ratio (UP/C) was greater in the EN group compared with the placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the change in UP/C from baseline was significantly different between groups (EN = -4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/- 15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5 mm Hg in the placebo group). Response to treatment was categorized as improvement (assigned a value of 2), no progression (assigned a value of 1), and progression (assigned a value of 0). Response was significantly better in the EN group (1.4 +/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest that EN treatment is beneficial in dogs with naturally occurring idiopathic GN.

Functional urethral obstruction in 3 dogs: clinical and urethral pressure profile findings.

Three dogs with dysuria and urine retention caused by excessive functional urethral resistance are described. All dogs had clinical histories and urologic signs that previously would have been classified as detrusor-urethral dyssynergia. Diagnosis of functional urinary obstruction was established by exclusion of anatomic urinary obstruction and confirmed by urethral pressure profilometry. In 2 cases, multiple pressure deflections recorded in the urethral pressure profile suggested spasm of urethral musculature, whereas in a 3rd dog, abnormally high pressures were recorded along a portion of the proximal urethra. Functional urinary obstruction was associated with prostatitis in 1 dog and with a history of urethral calculi in 1 dog, and no underlying disorder could be identified in the remaining dog. All 3 dogs improved with medical treatments that included alpha adrenergic antagonists. The etiology, diagnosis, and pharmacologic management of functional urinary obstruction are discussed.

Fluid therapy in acute and chronic renal failure.

Fluid therapy is one of the mainstays of treatment for renal failure, and rehydration is the primary goal. In those patients with ARF or "acute on chronic" decompensated CRF, induction of a diuresis to facilitate renal excretory function is important. Measurement of urine production in these patients helps guide fluid and electrolyte therapy. In oliguric renal failure, retention of water and electrolytes is likely, whereas in nonoliguric ARF as well as CRF, loss of water and electrolytes is the primary concern.

Safety and efficacy of 4-methylpyrazole for treatment of suspected or confirmed ethylene glycol intoxication in dogs: 107 cases (1983-1995).

OBJECTIVE: To evaluate safety and efficacy of 4-methylpyrazole (4-MP) treatment in dogs and to determine clinical signs and outcome of, and clinicopathologic abnormalities in, dogs treated in early or late stages of ethylene glycol (EG) intoxication. DESIGN: Retrospective study. ANIMALS: 107 dogs. PROCEDURE: For dogs treated with 4-MP, 1 of 2 dosage regimens was usually used: 20 mg/kg of body weight, IV, initially, 15 mg/kg 17 hours later, and 5 mg/kg 25 and 36 hours after the initial dose, or 20 mg/kg, IV, initially, 15 mg/kg 12 and 24 hours later, and 5 mg/kg 36 hours after the initial dose. RESULTS: Neither adverse clinical signs nor clinicopathologic abnormalities were associated with the administration of 4-MP except in 1 dog, which developed tachypnea, gagging, excess salivation, and trembling after the second dose of 4-MP was given. Ethylene glycol intoxication was confirmed in 37 dogs. Of these, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived. All 16 dogs that did not become azotemic survived. Median time from EG ingestion to treatment with 4-MP was 5 hours (range, 2 to 8.5 hours) for dogs that were not azotemic at admission and 14.5 hours (range, 8.5 to 38 hours) for dogs that were azotemic at admission. CLINICAL IMPLICATIONS: 4-MP was a safe and effective treatment for EG intoxication when it was given before sufficient quantities of EG had been metabolized to induce renal failure. Dogs treated within 8 hours of EG ingestion had a good prognosis.

Prevention of acute renal failure.

Acute renal failure (ARF) induced by therapeutic agents that are nephrotoxic (e.g., gentamicin, cisplatin, amphotericin, and nonsteroidal anti-inflammatory drugs) or hypotension associated with anesthesia and surgery unfortunately occur with some regularity in small animal practice. Several clinical conditions have been identified that can increase the risk of hospital-acquired ARF in dogs. Recognition of these risk factors allows the clinician to assess the risk/benefit ratio for various drugs and/or procedures. Additionally, initiating protective measures and increasing the monitoring of renal function in those patients that require potentially harmful treatment may decrease the incidence of hospital-acquired ARF.

Effects of dietary n-3 fatty acid supplementation versus thromboxane synthetase inhibition on gentamicin-induced nephrotoxicosis in healthy male dogs.

OBJECTIVE: To evaluate the protective effects of dietary n-3 fatty acid supplementation versus treatment with a thromboxane synthetase inhibitor (TXSI) in dogs given high-dose gentamicin. DESIGN: Clinicopathologic and renal histopathologic changes induced by gentamicin (10 mg/kg of body weight, IM, q 8 h, for 8 days) were compared in dogs fed an n-3 fatty acid-supplemented diet containing a fatty acid ratio of 5.7:1 (n-6:n-3), dogs treated with CGS 12970 (a specific TXSI given at 30 mg/kg, PO, q 8 h, beginning 2 days prior to gentamicin administration), and control dogs. The TXSI-treated and control dogs were fed a diet with a fatty acid ratio of 51.5:1 (n-6:n-3). Both diets were fed beginning 42 days prior to and during the 8-day course of gentamicin administration. ANIMALS: Eighteen 6-month-old male Beagles, 6 in each group. RESULTS: After 8 days of gentamicin administration, differences existed among groups. Compared with n-3-supplemented and control dogs. TXSI-treated dogs had higher creatinine clearance. Both TXSI-treated and n-3-supplemented dogs had higher urinary prostaglandin E2 and E3 (PGE2/3) and 6-keto prostaglandin F1a (PGF1a) excretion, compared with control dogs. Urinary thromboxane B2 (TXB2) excretion was higher in n-3-supplemented and control dogs, compared with TXSI-treated dogs. Urine PGE2/3-to-TXB2 and PGF(in)-to-TXB2, ratios were increased in TXSI-treated dogs, compared with n-3-supplemented and control dogs, and these ratios were increased in n-3-supplemented dogs, compared with control dogs. In addition, TXSI-treated and n-3-supplemented dogs had lower urinary protein excretion, compared with control dogs. Proximal tubular necrosis was less severe in TXSI-treated dogs, compared with control dogs. CONCLUSION: Treatment with CGS 12970 prior to and during gentamicin administration prevented increases in urinary TXB2 excretion and reduced nephrotoxicosis. CLINICAL RELEVANCE: Increased renal production/excretion of thromboxane is important in the pathogenesis of gentamicin-induced nephrotoxicosis.

Hospital-acquired acute renal failure in dogs: 29 cases (1983-1992).

OBJECTIVE: To assess factors associated with development of hospital-acquired acute renal failure (HARF) and to determine outcome of and prognostic indicators for dogs with HARF. DESIGN: Retrospective case series. ANIMALS: 29 dogs. RESULTS: The most common inciting causes for developments of HARF were exposure to a nephrotoxicant and advanced age. Mortality was 62%, and factors that contributed to mortality were age and initial urine output. Dogs > or = 7 years old and dogs that were initially oliguric had an odds ratio of mortality of 8.8 and 20, respectively. The effect of preexisting heart disease on mortality approached significance (P = 0.053). The magnitude of azotemia at the time of diagnosis was not related to the chance for survival. Dogs that died had a significantly higher initial anion gap and serum phosphorus concentration than did dogs that survived. We did not detect a relationship between cause of HARF and outcome (survived vs died or euthanatized). CLINICAL IMPLICATIONS: In most cases, HARF is associated with a poor outcome. Older dogs may be at increased risk for development of HARF, and once HARF has developed, have a greater chance of dying. Prognosis can not be determined on the magnitude of azotemia at the time of diagnosis or on the inciting cause of HARF.

Comparison of the effects of diltiazem and aspirin on platelet aggregation in cats.

Platelet aggregation in response to collagen (1 or 3 micrograms/ml), arachidonic acid (10(-2) M), and adenosine diphosphate (ADP, 2 microM) was compared in healthy cats treated with diltiazem (approximately 2 mg/kg body weight, q 8 hrs for 10 doses), aspirin (approximately 21 mg/kg body weight [1 baby aspirin], q 72 hrs for three doses), or a combination of diltiazem and aspirin. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood resulted in an impedance change (i.e., aggregation) with time in samples from the nontreated cats and the cats treated with diltiazem, but the addition had no effect in blood from cats treated with aspirin alone or with a combination of diltiazem and aspirin. Platelet aggregation in response to either concentration of collagen or to ADP was not altered by any treatment. Secretion of adenosine triphosphate (ATP) from the platelets was measured when the aggregating agent was 3 micrograms/ml collagen; secretion was not affected by any treatment.

Estimation of quantitative enzymuria in dogs with gentamicin-induced nephrotoxicosis using urine enzyme/creatinine ratios from spot urine samples.

The correlation between 24-hour urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) with urine NAG and GGT/creatinine ratios was assessed in dogs with gentamicin-induced nephrotoxicosis. Eighteen 6-month-old male Beagles with normal renal function were randomly divided into 3 groups of 6. Each group was fed a different concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued on its respective diet. Endogenous creatinine clearance and 24-hour urinary excretion of NAG and GGT were determined after dietary conditioning (day 0) and on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and GGT/creatinine ratios (IU/L divided by mg/dL) were determined from catheterized spot urine samples obtained between 7 and 10 AM on the same days. The correlation between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the spot urine samples was evaluated by simple linear regression analysis. Spot sample urine enzyme/creatinine ratios were significantly correlated with 24-hour urinary enzyme excretion through day 4 for dogs on low dietary protein, through day 6 for those on medium protein, and through day 8 for those on high dietary protein. Mean +/- SD baseline values for urine NAG/creatinine ratio and 24-hour urinary NAG excretion were 0.06 +/- 0.04 and 0.19 +/- 0.14 IU/kg/24 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs.

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs.

Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin-treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)