Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital

The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1, 5, 7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.     

Plication of the free wall of the left ventricle in dogs with doxorubicin-induced cardiomyopathy

OBJECTIVE: To evaluate plication of the free wall of the left ventricle, which reduces the left ventricular area and volume, as a method to improve the left ventricular systolic function without cardiopulmonary bypass. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dilated cardiomyopathy (DCM) was induced in each dog by administration of doxorubicin (30 mg/m2, i.v., q 21 d for 168 days).Two dogs died during induction of cardiomyopathy. Plication surgery was performed in 4 dogs. Two dogs did not ondergo to surgery (control group). Values for cardiac output (CO), 2-dimensional and M-mode echocardiography, arterial blood pressure, electrocardiography, blood cell counts, and serum biochemical analyses were recorded after induction of DCM (baseline) and 1, 2, 7, 15, 21, 30, 60, 90, 120, 150, and 180 days after plication surgery. Ambulatory ECG (Holter) recordings were conducted for 24 hours on the day of surgery. RESULTS: 1 dog died after plication surgery. The remaining dogs undergoing ventricular plication had a significant improvement in CO, ejection fraction, and fractional shortening and reductions of left ventricular area and volume after surgery. Electrocardiographic and Holter recordings revealed premature ventricular complexes, which resolved without treatment during the first week after surgery. Clinical condition of the control dogs declined, and these 2 dogs died approximately 40 days after induction of cardiomyopathy. CONCLUSIONS AND CLINICAL RELEVANCE: Plication of the free wall of the left ventricle improved left ventricular systolic function in dogs with doxorubicin-induced cardiomyopathy. Additional studies are needed to evaluate its application in dogs with naturally developing DCM.     

Value of echocardiography and electrocardiography as screening tools prior to Doxorubicin administration

The dose-limiting toxicity of doxorubicin is cardiotoxicosis. The authors of this report hypothesized that by using their institution's adopted guidelines (that involve prescreening echocardiography and electrocardiography), they would detect pre-existing cardiac abnormalities that preclude doxorubicin administration in <10% of dogs. Of 101 dogs, only 6 were excluded from doxorubicin administration based on electrocardiogram abnormalities, with a majority of those arrhythmias classified as ventricular premature contractions. One patient was excluded based on echocardiogram alone due to hypertrophic cardiomyopathy. The incidence of cardiotoxicity in treated dogs was 8% (8/101). Additional pretreatment and ongoing studies are indicated to identify risk factors for cardiotoxicity.     

Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alone for multicentric lymphoma in dogs

OBJECTIVE: To evaluate the antitumor and toxic effects of treatment with doxorubicin combined with piroxicam or doxorubicin alone for multicentric lymphoma in dogs. DESIGN: Nonrandomized clinical trial. ANIMALS: 75 dogs with multicentric lymphoma. PROCEDURE: 33 dogs were treated with doxorubicin (30 mg/m2, IV, q 21 d, for 3 doses) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h); results were compared with a historical control group of 42 dogs treated with doxorubicin (30 mg/M2, IV, q 21 d, for 3 doses) alone. Results-The percentages of dogs that had remission with doxorubicin-piroxicam treatment (79%) or doxorubicin treatment alone (74%) were not significantly different. Median duration of first remission was 130 days with doxorubicin-piroxicam and 147 days with doxorubicin alone; these values were not significantly different. Severe toxicosis was observed in 22% of dogs treated with doxorubicin-piroxicam and 17% of dogs treated with doxorubicin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Both treatment protocols were efficacious and well tolerated. The doxorubicin-piroxicam treatment was no more effective regarding response rate, remission duration, or survival duration, compared with the control group treated with doxorubicin alone.     

Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs

OBJECTIVE: To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE: Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS: Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.     

Doxorubicin-lnduced Cardiotoxicosis Clinical Features in 32 Dogs

Clinical cardiac abnormalities developed in 32 of 175 dogs that had various malignancies and were treated with doxorubicin: 31 dogs had electrocardiographic abnormalities including arrhythmias and nonspecific alterations in the R wave, ST segment, or QRS duration and 7 dogs had congestive heart failure. All seven dogs that had congestive heart failure died within 90 days. At necropsy, 13 of 32 affected dogs had noninflammatory myocardial degeneration, myocytolysis, vacuolation, and/or fibrosis and there was intramural coronary arteriosclerosis in all 13. Five dogs with lymphosarcoma were in complete clinical remission when they died of doxorubicin-induced cardiomyopathy, but the overall survival times of the lymphosarcoma subset was nevertheless longer than in previous studies. The clinical use of doxorubicin in the dog can cause cardiotoxicosis but the therapeutic benefit appears to outweigh risks in most dogs.     

Phase I Evaluation of Doxorubicin and Whole-body Hyperthermia in Dogs with Lymphoma

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiographic evaluation of diastolic parameters in dogs with dilated cardiomyopathy

Echocardiography is a valuable tool for the evaluation of systolic and diastolic cardiac function. A high correlation between measurements of diastolic mitral inflow parameters analyzed with Doppler echocardiography and invasive methods makes the former valuable. The aim of this study was to ascertain if significant differences occur in diastolic myocardial parameters between dogs with no heart disease and dogs with subclinical or clinical dilated cardiomyopathy. Furthermore the aim of the study was to determine whether heart failure in dilated cardiomypathy is a result of systolic dysfunction alone or both systolic and diastolic dysfunction. Eleven parameters were analyzed: E wave, E-AT, E-DT, E time, A wave, A-AT, A-DT, A time, E+A time, E/A ratio, and IVRT. The study confirmed the value of noninvasive echocardiographic assessment of diastolic function in dogs with dilated cardiomyopathy. Significant differences were found in E wave, E-AT, E time, E/A ratio and IVRT between healthy dogs and dogs with dilated cardiomyopathy. All are characterized by a significant decrease compared to healthy dogs after taking into account age and body weight except for the E/A ratio, which significantly increased in value. There were no significant changes in any of the Doppler parameters for diastolic evaluation in subclinical cases of DCM. Advanced heart failure in dilated cardiomyopathy entails systolic and diastolic dysfunction.     

Anthracycline-induced cardiomyopathy in a dog treated with epirubicin

An 8-year-old American cocker spaniel dog was diagnosed with dilated cardiomyopathy. Four years earlier, the dog had been diagnosed with multicentric lymphoma and had received 4 cycles of multi-agent chemotherapy, including doxorubicin and epirubicin. The total cumulative dose of epirubicin was 168 mg/m². Dilated cardiomyopathy was considered a consequence of epirubicin toxicity.     

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118 client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.     

Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs.

Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of western immunoblot for evaluation of myocardial dystrophin, alpha-sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy

OBJECTIVE: To evaluate the potential importance of dystrophin, alpha-sarcoglycan (adhalin), and beta-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy. SAMPLE POPULATION: Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound). PROCEDURE: Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, alpha-sarcoglycan and beta-dystroglycan. RESULTS: Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities in dystrophin, alpha-sarcoglycan, and beta-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention.     

The Acute Hemodynamic Effects of Milrinone in Dogs With Severe Idiopathic Myocardial Failure

To examine the effects of acute oral milrinone administration (0.75 mg/kg) on dogs with severe idiopathic myocardial failure and the effect of prolonged milrinone administration on survival time, we measured hemodynamics before and 2 hours after drug administration and recorded survival time and cause of death in 13 dogs with dilated cardiomyopathy. Hemodynamics were measured using a Swan-Ganz catheter and femoral artery puncture along with recording an M-mode echocardiogram. Cardiac index increased from 1.92 +/- 0.54 to 3.06 +/- 0.81 L/min/m2, stroke volume index increased from 11.3 +/- 4.3 to 16.7 +/- 6.3 ml/beat/m2, and pulmonary capillary wedge pressure decreased from 23 +/- 8 to 12 +/- 8 mmHg. A clinically significant increase in heart rate was observed in seven dogs, resulting in a statistically significant increase in heart rate for the group from 174 +/- 34 to 194 +/- 44 beats/minute. Mean arterial blood pressure did not change significantly for the group but did decrease more than 20 mmHg in three dogs, suggesting a predominant primary vasodilating effect of milrinone in these dogs. An increase in contractility appeared to be the predominant reason for the improved hemodynamics in seven dogs. Eight dogs died of causes other than worsening heart failure, including four of eight Doberman pinschers that died suddenly, presumably from an acute tachyarrhythmia. Two dogs that had the greatest increase in an index of contractility are alive more than 2 years after the initiation of milrinone administration.     

Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma

Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.     

Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs

OBJECTIVE: To determine sedative and cardiorespiratory effects of i.m. administration of medetomidine alone and in combination with butorphanol or ketamine in dogs. DESIGN: Randomized, crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs were given medetomidine alone (30 micrograms/kg [13.6 micrograms/lb] of body weight, i.m.), a combination of medetomidine (30 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or a combination of medetomidine (30 micrograms/kg, i.m.) and ketamine (3 mg/kg [1.36 mg/lb], i.m.). Treatments were administered in random order with a minimum of 1 week between treatments. Glycopyrrolate was given at the same time. Atipamezole (150 micrograms/kg [68 micrograms/lb], i.m.) was given 40 minutes after administration of medetomidine. RESULTS: All but 1 dog (given medetomidine alone) assumed lateral recumbency within 6 minutes after drug administration. Endotracheal intubation was significantly more difficult when dogs were given medetomidine alone than when given medetomidine and butorphanol. At all evaluation times, percentages of dogs with positive responses to tail clamping or to needle pricks in the cervical region, shoulder region, abdominal region, or hindquarters were not significantly different among drug treatments. The Paco2 was significantly higher and the arterial pH and Pao2 were significantly lower when dogs were given medetomidine and butorphanol or medetomidine and ketamine than when they were given medetomidine alone. Recovery quality following atipamezole administration was unsatisfactory in 1 dog when given medetomidine and ketamine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of medetomidine with butorphanol or ketamine resulted in more reliable and uniform sedation in dogs than did medetomidine alone.     

Effects of dilated cardiomyopathy on the renin-angiotensin-aldosterone system, atrial natriuretic peptide activity, and thyroid hormone concentrations in dogs

OBJECTIVE: To evaluate the effect of dilated cardiomyopathy (DCM) on activity of the renin-angiotensin-aldosterone system (RAAS), the N-terminal fragment of proatrial natriuretic peptide (NT-proANP), and thyroid hormone concentrations in dogs. ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs without clinical signs of DCM, and 15 age-, breed-, and sex-matched control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs, and blood and urine samples were collected. RESULTS: Plasma renin activity (PRA), plasma aldosterone concentration (PAC), urine aldosterone-to-creatinine ratio, and NT-proANP concentrations were significantly increased in dogs with clinical signs of DCM, compared with dogs without clinical signs and control dogs. Thyroid-stimulating hormone and total thyroxine concentrations did not differ significantly among groups; however, free thyroxine (FT4) concentrations were significantly decreased in dogs with clinical signs of DCM, compared with control dogs and DCM-dogs without clinical signs. Concentrations of PRA, PAC, FT4, and urine aldosterone-to-creatinine ratio were significantly correlated, whereas plasma concentrations of NT-proANP only correlated with FT4 concentration. CONCLUSION AND CLINICAL RELEVANCE: In dogs with clinical signs of DCM, increased concentrations of components of the RAAS were associated with increased concentrations of NT-proANP Analysis of the neurohormonal system may aid in identification of clinical stages of DCM for groups of dogs, but the range is too great and there are too many dogs that have neurohormonal concentrations within reference ranges to assess dogs on an individual basis.     

Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin

OBJECTIVE: To determine the effectiveness and safety of asparaginase administered s.c. versus i.m. for treatment of multicentric lymphoma in dogs receiving doxorubicin. DESIGN: Prospective study. ANIMALS: 49 dogs with multicentric lymphoma. PROCEDURE: Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, s.c. or i.m. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered s.c. in 23 dogs and i.m. in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses. RESULTS: Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between s.c. and i.m. groups. For dogs in clinical stage IV, i.m. administration of asparaginase significantly decreased the number of days to complete remission, compared with s.c. administration (8 vs 17 days, respectively). For dogs in clinical stage III, i.m. administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated i.m. had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated s.c. Asparaginase toxicoses were not observed regardless of the route of administration. CLINICAL IMPLICATIONS: For dogs with multicentric lymphoma that are receiving doxorubicin, i.m. treatment with asparaginase is more effective than s.c. treatment.     

Detection of attenuated wavy fibers in the myocardium of Newfoundlands without clinical or echocardiographic evidence of heart disease

OBJECTIVES: To determine whether attenuated wavy fibers may be found in the myocardium of Newfoundlands without clinical or echocardiographic evidence of heart disease. ANIMALS: 15 Newfoundlands from a kennel with a known predisposition to dilated cardiomyopathy (DCM) and 32 dogs of other breeds that died suddenly or were euthanatized for reasons unrelated to heart disease and did not have gross postmortem evidence of heart disease. PROCEDURE: Echocardiography was performed on all Newfoundlands on a yearly basis. Necropsy specimens from all dogs were evaluated for attenuated wavy fibers (i.e., myocardial cells <6 microm in diameter with a wavy appearance). RESULTS: None of the Newfoundlands had clinical signs of heart disease, and results of echocardiographic examinations were within reference ranges. Seven Newfoundlands had histologic evidence of attenuated wavy fibers, whereas attenuated wavy fibers were not found in the remaining 8 Newfoundlands or in any of the 32 dogs of other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that attenuated wavy fibers in dogs with a known predisposition for DCM may indicate an early stage of the disease. However, further studies on a larger number of dogs are needed to confirm this hypothesis.     

Alterations in Lipoprotein Profiles in Dogs With Lymphoma

After a 12-hour fast, blood samples were obtained from 31 dogs with previously untreated lymphoma. Blood samples were also collected from 16 of these dogs after up to 5 treatments with doxorubicin (30 mg/m² intravenously every 3 weeks). All 16 dogs underwent complete remission. Five dogs were re-evaluated after relapse and after overt signs of cancer cachexia had become clinically apparent. Samples were assayed for 8 quantitative parameters: total cholesterol (T-CH) and total triglyceride (T-TG) concentrations, and the concentration of cholesterol and triglyceride in each of the three major lipoprotein fractions, very-low-density lipoprotein (VLDL-CH and VLDL-TG), low-density lipoprotein (LDL-CH and LDL-TG), and high-density lipoprotein (HDL-CH and HDL-TG). The results were compared with those from 20 healthy control dogs of similar weight and age before and 3 weeks after being given one dose of doxorubicin (30 mg/m² intravenously). The administration of doxorubicin to control dogs resulted in a significant (P> .05) decrease in T-CH, LDL-CH, and HDL-CH, as well as a significant increase in VLOL-TG and HDL-TG. When compared with untreated controls, untreated dogs with lymphoma had significantly higher concentrations of VLDL-CH, T-TG, VLDL-TG, LDL-TG, and HDL-TG, and significantly lower concentrations of HDL-CH. HDL-TG and VLDL-TG concentrations from dogs with lymphoma were significantly increased above pretreatment values after relapse and development of overt signs of cancer cachexia. Dogs in remission that were evaluated after one dose of doxorubicin had significantly higher concentrations of T-CH, VLDL-CH, T-TG, and LDL-TG when compared with controls that were evaluated after an identical dose of doxorubicin. HDL-TG increased significantly over pretreatment values in dogs with lymphoma after doxorubicin therapy. These results suggest that dogs with lymphoma have significant alterations in lipid profiles, and with the possible exception of HDL-CH, these abnormalities do not normalize when clinical remission is obtained.     

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.