Toxicity in Doberman Pinchers with ventricular arrhythmias treated with amiodarone (1996-2005).

BACKGROUND: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study. HYPOTHESIS: Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn. METHODS: Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs. RESULTS: Reversible toxicity was identified in 10 of 22 (45%) dogs. CONCLUSION AND CLINICAL IMPORTANCE: Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly.

Gingival hyperplasia associated with the administration of amlodipine to dogs with degenerative valvular disease (2004-2008).

BACKGROUND: Calcium channel blocking drugs, usually nifedipine and less often amlodipine, have been reported to cause gingival hyperplasia (GH) in humans. HYPOTHESIS: Amlodipine, a dihydropyridine calcium channel blocking drug, can cause GH when administered chronically to older small dogs with degenerative valvular disease. ANIMALS STUDIED: From January 2004 to May 2008, 82 client-owned dogs with degenerative valvular disease and left atrial dilatation were treated with amlodipine in combination with spironolactone and enalapril and followed for >6 months. METHODS: Retrospective study. A chronological observation of GH in 2 dogs treated with amlodipine in 2004 and 2006 prompted the study. Patient histories and medical records of each dog treated with amlodipine for degenerative valvular disease from January 2004 to May 2008 were reviewed. RESULTS: GH was observed by clients and the authors in 7 of 82 (8.5%) dogs. Histologic confirmation of the diagnosis was made in 2 dogs. The minimum duration of treatment before diagnosis of GH was 5 months. GH began to resolve within 2 weeks of discontinuing amlodipine and resolution was complete within 6 months. Amlodipine administration was reinstituted in 1 dog in which GH had resolved, and GH reoccurred within 4 months. CONCLUSION AND CLINICAL IMPORTANCE: Long-term administration of amlodipine to dogs with degenerative valvular disease may cause GH in a small percentage of patients. GH resolves quickly after withdrawal of amlodipine treatment.

Bradycardia-associated syncope in 7 Boxers with ventricular tachycardia (2002-2005).

BACKGROUND: Syncope is a recognized problem in Boxers and often is the result of rapid ventricular tachycardia (VT). Affected dogs may have echocardiographic evidence of dilated cardiomyopathy, but frequently have normal echocardiograms. Although VT is probably the most common cause of syncope in Boxers, neurocardiogenic bradycardia can also occur. OBJECTIVE: We describe 7 Boxers with comorbid VT and neurocardiogenic bradycardia, wherein the syncope was secondary to bradycardia rather than VT. ANIMALS: Seven Boxers were selected from a larger population of Boxers with Holter-documented VT because these dogs had documented bradycardia at the time of syncope. METHODS: Retrospective study. RESULTS: Although all dogs had Holter-documented VT, the etiology of the syncopal episodes was consistent with neurocardiogenic bradycardia. CLINICAL IMPORTANCE: Neurocardiogenic bradycardia or VT can occur as isolated problems in Boxers. In some Boxers, VT and potential or manifest neurocardiogenic bradycardia coexist. The administration of a beta-blocker or sotalol to such dogs can aggravate or precipitate neurocardiogenic bradycardia-related syncope.

Efficacy and toxicity of tocainide for the treatment of ventricular tachyarrhythmias in Doberman pinschers with occult cardiomyopathy.

Tocainide was administered to 23 cardiomyopathic Doberman Pinschers at doses of 15 to 25 mg/kg tid. These doses produced peak (2-hour) serum concentrations of 6.2 to 19.1 mg/L and trough (8-hour) serum concentrations of 2.3 to 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 to 25.0 mg/kg) that were not different from those (16.0 to 26.0 mg/kg) received by dogs that did not experience toxicity. Doses producing peak serum concentrations that were either greater or less than 14 mg/L were not different. Likewise, doses producing trough values that were either greater or less than 6 mg/L were not different. The mean dose that produced peak serum concentrations of 10 to 13.6 mg/L and trough concentrations of 4.2 to 10.0 mg/L was 17.9 mg/kg, and was associated with anorexia in 4 dogs. Mean peak serum concentrations associated with toxicity (14.4 mg/L) were significantly higher (P = .02) than dogs not experiencing toxicity (11.8 mg/L). Serious adverse effects occurred in 7 of 12 dogs (58%) receiving tocainide for longer than 4 consecutive months. Progressive corneal endothelial dystrophy occurred in 3 dogs. Although a causal effect could not be proven, 6 dogs experienced renal dysfunction during treatment. Drug doses in these 7 dogs were similar to those received by other dogs. At least a 70% reduction of the total numbers of ventricular premature contractions occurred in 80% of dogs treated, and ventricular tachycardia was eliminated in 90% of affected dogs by the time of the first posttreatment Holter recording. Long-term control of ventricular tachyarrhythmias was difficult to achieve in some dogs when the left ventricular shortening fraction was less than approximately 17%.

Signalment, survival, and prognostic factors in Doberman pinschers with end-stage cardiomyopathy.

Congestive heart failure (CHF) was evaluated by retrospective review of case records of 66 Doberman Pinschers presenting with overt signs of 2 weeks' duration or less. Left-sided CHF was predominant, the majority of dogs were male, most were 5 to 10 years of age, and CHF tended to occur in females at an older age. Sudden death occurred in 13 dogs (20%). The mean and median survival times of all dogs were 9.65 and 6.5 weeks, respectively. Both atrial fibrillation and bilateral CHF at the time of presentation were associated with significantly shorter survival times.

Possible late potentials in 4 dogs with sustained ventricular tachycardia.

Signal-averaged electrocardiograms (SAEKGs) were performed on 4 dogs with sustained ventricular tachycardia. Quantitative and qualitative analyses of SAEKGs were consistent with the presence of late potentials. Two of the 4 dogs subsequently died suddenly, and ventricular tachycardia and ventricular fibrillation were observed in 1 dog. High-frequency QRS durations (75-90 milliseconds), duration of low amplitude (less than 40 microV) signals during the terminal QRS complex (LAS40) (28-40 milliseconds), root mean square voltages of the terminal 40 milliseconds of the QRS complex (RMS40) (124-6.5 microV), and root mean square voltages of the terminal 30 milliseconds of the QRS complex (RMS30) (13-2.1 microV) differed from results obtained in 68 of 70 control dogs. Echocardiographic data suggested dilated cardiomyopathy in 2 dogs and the cause of the arrhythmia in 2 dogs was not determined. The SAEKG may be a useful adjunct in identifying a subset of dogs with ventricular tachyarrhythmias that are at high risk for sustained ventricular tachycardia and sudden death. The sensitivity, specificity, and predictive accuracies of the technique remain to be determined.

Signal-averaged electrocardiograms in normal Doberman pinschers.

Signal-averaged electrocardiograms (SAECGs) were performed on nonsedated normal dogs in left-lateral recumbency. Following signal averaging, both time-domain and 3-dimensional frequency-domain analyses were performed. For time-domain analysis, the high-frequency QRS (HFQRS) duration, duration of the terminal QRS complex less than 40 microV (LAS40), and root mean square (RMS) voltages (microV) of the terminal 40 milliseconds (RMS40) and 30 milliseconds of the QRS complex were calculated. For frequency-domain analysis, correlation ratios were calculated for 30-, 40-, 50-, and 60-millisecond segment lengths begun 10, 15, or 20 milliseconds before the end of the QRS complex. Spectro-temporal mapping was also performed. All of the parameters of the SAECGs analyzed in the time domain were associated with each other. LAS40 and RMS voltages regressed significantly (P < .0000) on the HFQRS duration. Ninety-five percent of the HFQRSs were 55-75 milliseconds, 95% of the LAS40s were 9-26 milliseconds, and 95% of the RMS40 voltages were 177-444 microV. None of the SAECGs contained evidence of ventricular late potentials. Spectro-temporal maps were similar in each dog when the same segment lengths and starting points were compared. No evidence of ventricular late potentials was observed. Correlation ratios were lower when windowed segments included 15 or 20 milliseconds (versus 10 milliseconds) of the terminal QRS complex. When only 10 milliseconds of the terminal QRS complex were included in windowed segments, the mean correlation ratios for 30- and 40-millisecond segment lengths were > 0.8 and > 0.61 in 67% of all analyses, respectively.

Bradycardia-associated episodic weakness, syncope, and aborted sudden death in cardiomyopathic Doberman Pinschers.

Paradoxical sinus bradycardia and cardiac asystole resulted in episodic weakness, syncope, or aborted sudden cardiac death during exertion in 8 cardiomyopathic Doberman Pinschers. Bradycardias persisted for 1 to 2 minutes in 5 of 8 dogs, and were often followed by sinus tachycardia. Syncope was prolonged on multiple occasions in 5 dogs, and was accompanied by white, then cyanotic mucous membranes, mydriasis, and apparent sudden death.

Echocardiographic detection of flail left atrioventricular valve cusp from ruptured chordae tendineae in 4 dogs.

Echocardiography was used to identify a flail left atrioventricular valve cusp caused by ruptured chordae tendineae in each of 4 dogs; two-dimensional echocardiography was superior to M-mode echocardiography in identifying the flail cusps. The following findings on two-dimensional imaging were characteristic: the tip of the flail cusp extended beyond the line of left atrioventricular valve cusp closure and pointed toward the left atrium in systole; the tip was thrust into the left ventricle, and then toward the left ventricular outflow tract in diastole, forming a convex surface to the cusp, which faced toward the left ventricle. The flail motion of the left atrioventricular valve cusp was best observed in the right parasternal long axis or left apical four-chamber views, in a plane parallel to the long axis of the left ventricle and left atrium. Rupture of chordae tendineae leading to flail cusp was attributed to chronic valve degeneration (endocardiosis) in all 4 dogs. Echocardiographic or clinical diagnoses were confirmed by postmortem gross and microscopic studies in all dogs.

Thyroid-stimulating hormone stimulation tests in cardiomyopathic Doberman pinschers: a retrospective study.

Thyroid-stimulating hormone (TSH) response tests were performed in 152 Doberman Pinschers. Seventy-nine dogs had cardiomyopathy (46 were in congestive heart failure [CHF] and 33 were not in CHF). Seventy-three dogs were presented for noncardiac problems (15 with skin disease, 21 with neurologic disease, 20 with internal medicine disorders, and 17 with other problems), although some may have had cardiomyopathy. The TSH response test results in the cardiomyopathic group were interpreted as normal or euthyroid-sick in 45 (57%) dogs, abnormal in 23 (29%) dogs, and equivocal in 11 (14%) dogs. The prevalence of hypothyroidism in the CHF and non-CHF cardiomyopathy groups was not different. Among the dogs presented for noncardiac problems, 27 (37%) were assessed as normal or euthyroid-sick, 29 (40%) as hypothyroid, and 17 (23%) as equivocal. No significant differences were found in the prevalence of hypothyroid test results among the subgroups of these dogs. The prevalence of hypothyroidism was not higher in the cardiomyopathic group compared to the other group, and 63 and 49% of cardiomyopathic dogs with or without CHF, respectively, tested as either euthyroid or euthyroid-sick.

Correlations among time and frequency measures of heart rate variability recorded by use of a Holter monitor in overtly healthy Doberman pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To determine correlations between time-domain and frequency-domain variables of heart rate variability (HRV) derived from 24-hour recordings obtained by use of an ambulatory electrocardiographic recorder (Holter monitor). ANIMALS: 59 overtly healthy Doberman Pinschers (41 without echocardiographic evidence of cardiomyopathy and 18 with precongestive heart failure attributable to cardiomyopathy). PROCEDURE: The HRV was analyzed from 24-hour recordings. Variables were calculated from the entire 24-hour recording as well as 4 user-selected time epochs. Comparisons were made for total power to SD of normal beat-to-normal-beat (NN) intervals (SDNN), ultra-low frequency power to SD of the means of NN intervals, low-frequency power and very-low-frequency power to mean of the SD of NN intervals, and high-frequency (HF) power to the root mean square successive difference of NN intervals (RMSSD) and percentage of NN intervals that varied from the previous NN interval by > 50 milliseconds (PNN50). RESULTS: 58 of 66 (88%) comparisons revealed significant values, indicating that relationships between variables were not random (r > 0.7 in 41 of 66 [62%)) comparisons). Strong correlations (r > 0.8) were found between the square root of total power and SDNN and between HF power and RMSSD. CONCLUSIONS AND CLINICAL RELEVANCE: Time-domain surrogates for variables of frequency-domain analysis variables that correlated in the dogs reported here are the same ones that reportedly correlate in humans. When 24-hour recordings obtained by use of a Holter monitor are used to calculate HRV, SDNN and total power as well as RMSSD and HF power are interchangeable.

Heart rate variability in Doberman Pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To characterize the salient variables of the time-domain analysis of heart rate variability (HRV) in clinically normal Doberman Pinschers and to compare those variables with those of Doberman Pinschers with cardiomyopathy and mild to moderate myocardial failure. ANIMALS: 46 Doberman Pinschers. PROCEDURE: HRV was analyzed in the time-domain from 24-hour Holter recordings obtained from 28 Doberman Pinschers with normal echocardiograms and 18 Doberman Pinschers with echocardiograms consistent with mild to moderate myocardial failure. RESULTS: Significant differences in HRV variables between the 2 groups of dogs were not detected. The HRV was greater during the nighttime (12 AM to 6 AM), compared with the 24-hour day and an 18-hour (6 AM to 12 AM) period. CONCLUSIONS AND CLINICAL RELEVANCE: HRV of dogs with mild to moderate myocardial failure was not different from that of clinically normal dogs, because there were no disturbances of autonomic balance, baroreceptor function, and other factors that influence HRV in the dogs with cardiomyopathy, or the sensitivity of time-domain analysis was overwhelmed by normal sinus arrhythmia. The techniques now used to study HRV have important limitations, especially in dogs, and better noninvasive tests of autonomic function are needed.

Orientation and configuration of vectorcardiographic QRS loops from normal cats.

The orientations (angles) of mean QRS vectors were manually calculated from scaler orthogonal leads (I, aVf, V10; X, Y, Z) and from X-Y oscilloscope recordings from cats injected with ketamine and acetylpromazine. Those angles calculated from individually recorded leads (I, aVf, and V10) were from cats in right lateral and sternal recumbency. Leads, X, Y, and Z were recorded simultaneously from cats in the sternal recumbency. The oscilloscope recordings were derived from the X, Y, and Z leads. Arithmetic and maximal measurements from ECG scaler leads and maximal and half-area measurements from oscilloscopic recordings were used for calculations. Recordings from 15 cats and from 1 cat 15 times. Based on visual inspection of scattergrams, the X, Y, and Z vectors were not different in orientation from I, aVf, and V10 vectors. Orientation of oscilloscopic vectors were more variable than orientations of vectors calculated from scaler leads. Body position of the cat during recording did not affect mean values of angles derived from leads I, aVf, and V10. Type of measurements did not affect mean values. Variation of orientation was greater among cats than for the intraindividual vector orientations. Configuration and direction of QRS loops from 27 normal cats were also recorded. The greatest variation in loop configuration was in the frontal plane.

Immunosuppressive effects of cyclophosphamide, vincristine, and L-asparaginase in dogs.

The acute effects of cyclophosphamide, vincristine, and L-asparaginase on the humoral and cell-mediated immune responses in dogs were evaluated. Dogs were given a single dose of cyclophosphamide (10 mg/kg of body weight, IV), a single dose of vincristine (0.025 mg/kg, IV), a single dose of L-asparaginase (400 U/kg, IV), or a combination of these drugs at the aforementioned dosages administered simultaneously. The total number of leukocytes decreased significantly (P = less than 0.05) on posttreatment day 3 in the cyclophosphamide-treated dogs. Antibody responses and lymphocyte blastogenesis were not affected. A transient lymphopenia on posttreatment day 1 was the only response seen in the vincristine-treated dogs. Antibody responses to sheep RBC and lymphocyte blastogenesis were suppressed in the L-asparaginase-treated dogs. L-Asparaginase did not affect the antibody response to bovine serum albumin or peripheral blood leukocyte counts. Suppressed antibody responses to sheep RBC and to bovine serum albumin, depressed lymphocyte blastogenesis, and decreased numbers of all peripheral blood leukocytes were seen in dogs given the 3 drugs in combination.

Effects of acepromazine and buprenorphine on measured indices of the signal-averaged electrocardiogram in healthy dogs.

OBJECTIVES: To determine values for indices of signal-averaged electrocardiograms (SAECG) in healthy dogs, and to determine whether sedation with acepromazine and buprenorphine would alter these indices. ANIMALS: 15 healthy adult dogs. PROCEDURE: SAECG were recorded from each dog twice: prior to sedation and immediately after sedation with acepromazine (0.01 mg/kg of body weight, IV) and buprenorphine (0.007 mg/kg, IV). Time-domain methods were used to analyze the SAECG. All indices were calculated by use of a computer. Measured indices included QRS duration, duration of low-amplitude signals in the terminal part of the QRS complex, root mean square voltages of the terminal 30 and 40 milliseconds of the QRS complex, heart rate, and high-frequency noise levels. RESULTS: We did not detect significant differences between values measured when dogs were not sedated and values measured when dogs were sedated except in regard to heart rate (P = 0.0001) and high-frequency noise levels (P = 0.0004), which were lower when dogs were sedated. Late potentials were not visually identified in SAECG from any dog in this study. CONCLUSION AND CLINICAL RELEVANCE: Sedation facilitated recording of SAECG in dogs without altering the results.

Spectro-temporal mapping of the surface electrocardiogram in clinically normal dogs.

OBJECTIVES: To establish data for selected variables of the signal-averaged ECG and determine whether sedation affects segment lengths and points within the terminal QRS complex where windows began. SAMPLE POPULATION: Overtly healthy dogs with no detected abnormalities. PROCEDURE: Signal-averaged ECG (600 beats) were obtained from dogs in left-lateral recumbency, using X, Y, and Z leads with 26-gauge subdermal platinum electrodes. Frequency-domain analyses were performed by fast Fourier transform (FFT), using a post-processing computer software package. Analyses were extracted from 30-, 40-, and 50-millisecond windowed (Blackman-Harris) segments of the terminal 10 or 20 milliseconds of the QRS complex and ST segment. Correlation ratios were calculated by cross-correlation of frequency spectra of each FFT in the range of 40 to 200 Hz. The reference spectrum was the last FFT (nearest the T wave). Spectro-temporal maps were plotted for each analysis. RESULTS: Noise levels were < 1 microV. Sedation resulted in less noise and slower heart rate, but did not affect results. Correlation ratios were not different among 30-, 40-, and 50-millisecond segments, but were lower when 20 (vs 10) milliseconds of the terminal QRS was included. Spectro-temporal maps were similar in all subjects. CONCLUSIONS: Use of sedation facilitated the procedure without affecting results. Segment lengths of 40 and 50 milliseconds, beginning 10 milliseconds prior to the end of the QRS complex and analyzed in the range of 40 to 200 Hz, yielded correlation ratios > 67%, 95% of the time. CLINICAL RELEVANCE: Spectro-temporal mapping may identify dogs with ventricular late potentials (high-frequency signals commonly associated with myocardial fibrosis) that may be at increased risk of sudden death.

Lymphocyte blastogenesis in dogs with lymphosarcoma.

Mitogen-stimulated lymphocyte blastogenesis was evaluated, using lymphocytes from 37 dogs with multicentric lymphosarcoma. The majority of the test results was within a normal range, even for those dogs with more advanced disease. However, depressed lymphocyte blastogenesis, when present, almost always occurred in lymphocytes from dogs with clinical stage IV-B and V-B disease. Dogs weighing greater than 25 kg had a significantly (P = 0.04) higher occurrence of clinical stage IV or V disease as compared with dogs weighing less than 15 kg. Dogs with diffuse lymphocytic well-differentiated lymphoma were statistically more likely to be designated clinical stage III at the time of diagnosis, as compared with dogs with diffuse lymphocytic poorly differentiated lymphoma.

Failure of spectro-temporal mapping to detect ventricular late potentials in dogs.

OBJECTIVE: To determine whether ventricular late potentials (LP) identified by time-domain analysis (TDA) of the signal-averaged ECG could be identified by three-dimensional frequency-domain analysis (FDA). ANIMALS: 11 dogs (9 of which subsequently died suddenly) with ventricular tachyarrhythmias (10 with ventricular tachycardia) and abnormal TDA of the signal-averaged ECG. PROCEDURE: Signal-averaged ECG that were abnormal when analyzed in the time domain subsequently were processed further in the frequency domain. Correlation ratios were calculated, and spectro-temporal maps were plotted, which were then compared with control data. RESULTS: Three-dimensional FDA did not detect LP. CONCLUSIONS AND CLINICAL RELEVANCE: LP may be detectable by TDA of the signal-averaged ECG and may be a specific marker for VT and sudden death in some dogs. However, FDA by use of the method applied in this study is invalid.

Pneumonitis associated with occult heartworm disease in dogs.

Nine of 69 dogs with occult heartworm disease (13%) had allergic pneumonitis characterized by consistent clinical and radiographic signs. Although the clinical signs were severe, the degree of radiographic pulmonary arterial abnormalities was mild. Corticosteroid therapy resulted in rapid resolution of clinical and radiographic signs; thiacetarsamide therapy was then given without complications. This syndrome may not be recognized as heartworm-associated and may be confused with other disorders, some being associated with a poor prognosis and requiring different therapy.

Use of M-mode echocardiography in the diagnosis of congestive cardiomyopathy in Doberman pinschers.

M-mode echocardiography performed on 3 groups of Doberman Pinschers--healthy, early cardiomyopathy, and advanced cardiomyopathy (pulmonary edema present). Echocardiographic measurements in those dogs with advanced cardiomyopathy were typical of the disease in human beings and other breeds of dogs. Significant differences were detected between dogs with early cardiomyopathy and those with advanced disease. The E-point septal separation was determined to be the most sensitive and specific criterion for the recognition of early cardiomyopathy.