Comparison of single- versus seven-day Holter analysis for the identification of dilated cardiomyopathy predictive criteria in apparently healthy Doberman Pinscher dogs.

INTRODUCTION: The primary objective of this study was to test whether seven-day Holter recording improves the sensitivity of detecting dilated cardiomyopathy (DCM) predictive criteria (DCMp) compared with 24-h Holter recording in asymptomatic Doberman Pinscher (DP) dogs. ANIMALS: Twenty-eight asymptomatic DP dogs with normal echocardiographic examinations. METHODS: Dogs with normal echocardiographic examinations underwent seven-day Holter monitoring. The presence of ≥50 ventricular premature complexes and or ≥ one couplet/one triplet/one episode of ventricular tachycardia per 24-h period was considered positive for DCMp. RESULTS: Five dogs were positive on the first day, and an additional six dogs tested positive from day two to seven of the Holter recording. The number of dogs positive for DCMp detected by four days was significantly different (p = 0.031) compared with the first-day Holter recording. CONCLUSIONS: Seven-day Holter recording detected significantly more dogs with DCMp compared with the first-day Holter recording. Follow-up studies are warranted to evaluate the long-term accuracy of multiple-day Holter analysis in predicting the development of DCM in DP dogs.

Pericardial Effusion in a Dog with Pericardial Hemangiosarcoma.

An adult Jack Russel terrier dog presented for evaluation of large-volume peritoneal and pleural effusion. Echocardiography revealed scant pericardial effusion and abnormally thickened pericardium. Electrocardiography revealed complete atrioventricular block with junctional and ventricular escape beats and occasional ventricular premature complexes. Computed tomography of the thorax confirmed diffuse abnormal thickening of the pericardium, and a tentative diagnosis of constrictive-effusive pericarditis was made. The dog underwent subtotal pericardiectomy to remove the parietal pericardium and permanent epicardial pacemaker implantation to manage bradycardia. Based on pericardial histopathology and immunohistochemistry, a diagnosis of pericardial hemangiosarcoma was made. Systemic chemotherapy was initiated with doxorubicin 1 month after surgery. Despite initial improvement with chemotherapy, the dog was euthanized 4 months after surgery because of development of recurrent pleural effusion. To the author's knowledge, this is the first case report in dogs to describe isolated pericardial location of hemangiosarcoma resulting in constrictive-effusive pericarditis.

Effects of prenatal bisphenol-A exposure and postnatal overfeeding on cardiovascular function in female sheep.

Bisphenol-A (BPA) is a widely used endocrine-disrupting chemical. Prenatal exposure to BPA is known to affect birth weight, but its impact on the cardiovascular system has not been studied in detail. In this study, we investigated the effects of prenatal BPA treatment and its interaction with postnatal overfeeding on the cardiovascular system. Pregnant sheep were given daily subcutaneous injections of corn oil (control) or BPA (0.5 mg/kg/day in corn oil) from day 30 to day 90 of gestation. A subset of female offspring of these dams were overfed to increase body weight to ~30% over that of normal fed controls. Cardiovascular function was assessed using non-invasive echocardiography and cuff blood pressure (BP) monitoring at 21 months of age. Ventricular tissue was analyzed for gene expression of cardiac markers of hypertrophy and collagen at the end of the observation period. Prenatal BPA exposure had no significant effect on BP or morphometric measures. However, it increased atrial natriuretic peptide gene expression in the ventricles and reduced collagen expression in the right ventricle. Overfeeding produced a marked increase in body weight and BP. There were compensatory increases in left ventricular area and internal diameter. Prenatal BPA treatment produced a significant increase in interventricular septal thickness when animals were overfed. However, it appeared to block the increase in BP and left ventricular area caused by overfeeding. Taken together, these results suggest that prenatal BPA produces intrinsic changes in the heart that are capable of modulating morphological and functional parameters when animals become obese in later life.

Alternative methods for the measurement of the minimal ductal diameter of a patent ductus arteriosus in a dog.

A two and half-year-old, 24 kg, spayed female German Shepherd was presented for evaluation of a suspected patent ductus arteriosus (PDA). Transthoracic echocardiographic examination confirmed a left to right shunting PDA. Closure of the PDA was recommended, and the owners elected to have minimally invasive transcatheter closure of the PDA performed. Standard ductal angiography failed to provide adequate measurements of the minimal ductal diameter (MDD). Alternative methods of measuring the MDD using an angiography catheter and a balloon catheter were performed. The PDA was occluded using an Amplatz® Canine Ductal Occluder without complication. Further evaluation of these techniques is needed to determine the accuracy, overall clinical efficacy, and safety of using alternative methods for the measurement of the MDD of a PDA.

Avibactam and class C ß-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance.

Avibactam is a novel non-ß-lactam ß-lactamase inhibitor that inhibits a wide range of ß-lactamases. These include class A, class C, and some class D enzymes, which erode the activity of ß-lactam drugs in multidrug-resistant pathogens like Pseudomonas aeruginosa and Enterobacteriaceae spp. Avibactam is currently in clinical development in combination with the ß-lactam antibiotics ceftazidime, ceftaroline fosamil, and aztreonam. Avibactam has the potential to be the first ß-lactamase inhibitor that might provide activity against class C-mediated resistance, which represents a growing concern in both hospital- and community-acquired infections. Avibactam has an unusual mechanism of action: it is a covalent inhibitor that acts via ring opening, but in contrast to other currently used ß-lactamase inhibitors, this reaction is reversible. Here, we present a high-resolution structure of avibactam bound to a class C ß-lactamase, AmpC, from P. aeruginosa that provided insight into the mechanism of both acylation and recyclization in this enzyme class and highlighted the differences observed between class A and class C inhibition. Furthermore, variants resistant to avibactam that identified the residues important for inhibition were isolated. Finally, the structural information was used to predict effective inhibition by sequence analysis and functional studies of class C ß-lactamases from a large and diverse set of contemporary clinical isolates (P. aeruginosa and several Enterobacteriaceae spp.) obtained from recent infections to understand any preexisting variability in the binding pocket that might affect inhibition by avibactam.

Effect of autonomic blockade on ventricular repolarization shortening: response to behavioral stimulus in paced dogs.

Autonomic tone has been suggested to be a significant determinant of ventricular repolarization duration with both rate dependent and independent effects. Using the His bundle-paced dog, a model that eliminates the need for QT correction factors, we explored the rate-independent effects of sympathetic and parasympathetic blockade on ventricular repolarization shortening following an excitatory stimulus. Six male His bundle-paced beagle dogs were paced at 80 bpm and fitted with jackets, surface ECG electrodes, and radiotelemeters. Dogs were given propranolol, atropine methyl nitrate, or the appropriate control in a four-period crossover design. Doses were based on literature reviews and unpublished pharmacokinetic/pharmacodynamic modeling to provide efficacious beta- and parasympathetic blockade throughout the data collection period. Data collection began at 11 am and concluded at 11 am the following day, with event stimuli provided by investigators entering the room at 5 pm and at 7 am the following morning. One minute of ECG data were sampled every 15 min and these means were averaged to generate hourly means for the 24 hour data collection period. Treatment with atropine attenuated RT interval shortening when compared with the vehicle group at both the 5 pm and 7 am stimulus. In contrast, propranolol was not associated with significant effects on RT interval duration at either time point. These results suggest that parasympathetic withdrawal is the primary factor responsible during both awake hours (5 pm) and in the transition from deep sleep to the awake state (7 am) in the facilitation of RT interval shortening following an excitatory stimulus. The attenuation of RT interval shortening following atropine treatment may be a direct effect, or an indirect effect requiring an excited state to become evident. The use of a model that eliminates the need to apply correction factors to repolarization indices helps to clarify the role of the autonomic nervous system on ventricular repolarization.

Concentration of cardiac troponin I in a horse with a ruptured aortic regurgitation jet lesion and ventricular tachycardia.

An 18-year-old Thoroughbred gelding was evaluated because of sudden onset of ventricular tachycardia and signs of colic. Three years earlier, a diastolic decrescendo murmur, consistent with aortic regurgitation, had been detected, but the horse continued to perform well and compete successfully. Cardiac ultrasonographic examination revealed a defect in the interventricular septum below the aortic root, and serum concentrations of cardiac troponin I (cTnI) were higher than those measured in clinically normal horses. Repeated development of tachyarrhythmia during hospitalization prompted a decision to euthanatize the horse. A ruptured endocardial jet lesion below the aortic valve with formation of a cleft into the interventricular septum was found on necropsy. This report of increased serum cTnI concentrations in a horse with myocardial disease and our other findings suggest that assessment of cardiac troponin concentrations may be a useful tool in the evaluation of horses with suspected myocardial disease.

Short-term effects of ecadotril in dogs with induced congestive heart failure.

OBJECTIVE: To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs. ANIMALS: 6 conscious adult male dogs. PROCEDURES: Instruments were placed in dogs to measure left ventricular, aortic, and atrial blood pressures. Heart failure was induced by repeated coronary embolization with latex microspheres. Four times, and in random order, dogs were given vehicle or active drug (3, 10, or 30 mg/kg of body weight) orally. Hemodynamic variables, urine flow, and urinary electrolyte excretion were measured before and 30, 90, and 150 minutes, and 10 and 21 hours after drug administration. RESULTS: Changes in urine flow, heart rate, mean arterial pressure, or peak positive and negative rate of change in ventricular pressure were not apparent. Urinary sodium excretion significantly increased in response to the low and high doses of ecadotril but not in response to the 10 mg/kg dose. Left ventricular end diastolic pressure (LVEDP) consistently decreased in dose- and time-dependent manner. Maximal group-averaged reductions in LVEDP were 5.2, 8.1, and 10 mm Hg for the low, middle, and high doses, respectively. The magnitude of the decrease in LVEDP was not related to cumulative change in urine flow. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered ecadotril reduced left ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect. Ecadotril may be effective for alleviating clinical signs in dogs with left-sided heart failure and may be particularly beneficial for use in dogs that are refractory to traditional diuretic therapy.

Effect of 131I-induced hypothyroidism on indices of reproductive function in adult male dogs.

Hypothyroidism has been cited as a cause of infertility, abnormal semen quality, and poor libido in people and animals. The purpose of this study was to evaluate the effect of hypothyroidism on variables indicative of reproductive function in adult male dogs. Nine normal dogs were randomly assigned to 2 groups. Hypothyroidism was induced with 131I in 6 dogs. Three dogs remained untreated, normal, and euthyroid. Thyroid hormone concentrations, body weight, clinical signs, and reproductive function were determined for each dog every 3 months for 2 years. Reproductive function was assessed by determining daily sperm output, total scrotal width, spermatozoal motility and morphology, libido, and serum testosterone and luteinizing hormone concentration responses to exogenous gonadotropin-releasing hormone. The 131I-treated dogs developed clinical and laboratory signs of hypothyroidism. In the hypothyroid dogs, serum concentrations of thyroid hormones were consistently below the reference range and were significantly lower than that in the euthyroid dogs. There was no difference in reproductive function between the hypothyroid and euthyroid dogs. The results of this study show that 131I-induced hypothyroidism does not affect indices of reproductive function in adult male dogs.

Type-1 hypersensitivity reactions to Malassezia pachydermatis extracts in atopic dogs.

OBJECTIVE: To investigate the potential allergenic role of the yeast Malassezia pachydermatis in dogs with clinical diagnosis of atopic dermatitis. ANIMALS: 5 clinically normal nonatopic dogs, 10 atopic dogs with cytologic evidence of Malassezia dermatitis, and 12 atopic dogs without cytologic evidence of Malassezia dermatitis. PROCEDURE: A crude yeast extract was produced by disrupting the cell wall of M pachydermatis. The crude extract and 8 of its fractions, which were generated by fractionation in a high-performance liquid chromatography column, were injected along with 46 commercial allergens for intradermal allergy testing of normal and atopic sample populations. Significant difference between atopic populations was evaluated, using a threshold concentration of crude yeast extract that failed to induce wheal-and-flare responses in normal nonatopic dogs. RESULTS: Atopic dogs with cytologic evidence of Malassezia dermatitis had significantly greater wheal-and-flare reactions to intradermal injection of crude extract of M pachydermatis than did atopic dogs without cytologic evidence of Malassezia dermatitis. CONCLUSIONS: It is concluded that M pachydermatis is capable of promoting type-1 hypersensitivity reactions in dogs with an atopic dermatitis phenotype. CLINICAL RELEVANCE: Currently, Malassezia dermatitis is principally managed by use of antifungal chemotherapy. Because the yeast appears to be a contributing allergen in dogs with atopic dermatitis, hyposensitization with M pachydermatis extracts may offer a future alternative to extended or repeated episodic administration of antifungals for extended control of recurrent infections.

Surgical correction of late-onset Budd-Chiari-like syndrome in a dog.

An 18-month-old dog was examined because of ascites of 1 month's duration. Typical causes of ascites, including hepatic failure, heart failure, and protein-losing enteropathy, were ruled out. The dog's history included being hit by a car 6 months earlier, and the caudal vena cava had an S shape on thoracic radiographs. In addition, the abdominal fluid had a high protein concentration and low cellular content. These findings were all consistent with a diagnosis of postsinusoidal hypertension secondary to obstruction of hepatic venous outflow (Budd-Chiari-like syndrome). During exploratory thoracotomy, the pericardium appeared to have been torn from the heart and was partially wrapped around the caudal vena cava, causing a constriction. The pericardium was removed and the dog recovered without any further complications. Blunt trauma has been previously reported to cause kinking of the caudal vena cava and Budd-Chiari-like syndrome in dogs; but in these dogs, clinical signs of ascites developed a few days to several weeks after the traumatic incident. It appears that, depending on the cause of the hepatic venous outflow obstruction, onset of Budd-Chiari-like syndrome may be delayed for months.

Evaluation of the sensitivity and specificity of diagnostic criteria for sepsis in dogs.

OBJECTIVE: To evaluate the ability of various individual criteria and grouped criteria to diagnose sepsis in dogs. STUDY DESIGN: Prospective acquisition of clinical data. ANIMALS OR SAMPLE POPULATION: Client-owned dogs; 30 septic and 320 nonseptic. METHODS: Rectal temperature, heart rate, respiratory rate, white blood cell (WBC) count with percent bands, platelet count, and serum glucose concentration were obtained on day 0. True sepsis was determined on days 0 to 3 according to the following criteria: (1) histological, microbiological, and/or gross confirmation of infection, and (2) systemic illness caused by infection. Data were analyzed by the Mann-Whitney U test and multiple logistic regression. Sensitivity and specificity were calculated. RESULTS: The mean temperature, heart rate, WBC count, and percent bands were greater, whereas the mean platelet count was less in septic compared with nonseptic dogs. There was no difference in respiratory rate or glucose concentration. WBC/bands were the best individual criterion for the diagnosis of sepsis (sensitivity 87%; specificity 69%). The sensitivity and specificity of the grouped criteria (> or = two of four; temperature, heart rate, respiratory rate, WBC) varied according to ranges of normal used. Multiple logistic regression resulted in little improvement in the sensitivity/specificity of these diagnostic criteria for the diagnosis of sepsis. CONCLUSIONS: These criteria are useful for the diagnosis of sepsis when limits are used that result in a high sensitivity (e.g., 97%). The high sensitivity was associated with a low false-negative and a high false-positive rate; sepsis was overdiagnosed with these grouped criteria. CLINICAL RELEVANCE: These criteria may be used for a sensitive, but nonspecific, diagnosis of sepsis in dogs.

Quantity and distribution of Malassezia organisms on the skin of clinically normal dogs.

OBJECTIVE: To define the extent to which Malassezia organisms can be recovered from the skin of clinically normal dogs and to assess differences in organism recovery related to anatomic sampling site and to method of collection. DESIGN: Prospective, controlled study. ANIMALS: 19 clinically normal dogs. PROCEDURE: The number of Malassezia pachydermatis organisms were determined in fungal cultures of samples obtained from the skin of clinically normal dogs, using an adhesive tape method to obtain samples from 10 sites/dog. Additionally, 3 methods (direct impression, swabbing technique, and superficial skin scraping) that are commonly used for obtaining samples for cytologic examination were evaluated. RESULTS: Malassezia organisms were found in low numbers as part of the microflora of the skin of clinically normal dogs. Number of organisms differed significantly for various anatomic locations (chin, highest number; inguinal and axillary regions, lowest number). Malassezia organisms were identified more frequently by use of adhesive tape and fungal culturing than by the methods used for cytologic examination. However, comparing methods used for obtaining samples for cytologic examination with each other, marked differences were not detected in our ability to recover yeast organisms among the 3 techniques. CLINICAL IMPLICATIONS: Although Malassezia spp is part of the microflora of the skin of clinically normal dogs, it is extremely difficult to detect the organism by any of the 3 sampling methods used for sample collection for cytologic examination. Therefore, anatomic site and method of sample collection should be considered when attempting to make a diagnosis of Malassezia dermatitis.

Noninvasive kinematic analysis of the walk in healthy large-breed dogs.

OBJECTIVES: To use computer-assisted kinematic analysis to describe the walk in healthy dogs and to adapt Fourier transformation for analysis of the data. DESIGN: Evaluation of normal walk in dogs, using kinematic and force plate analysis. SAMPLE POPULATION: 15 healthy large-breed dogs. PROCEDURE: Morphometric data were collected to describe the sample population. Temporal and distance variables were measured to describe the walk. Flexion and extension movements were described for the scapulohumeral, cubital, carpal, coxofemoral, femorotibial, and tarsal joints. Fourier transformation was adapted to facilitate analysis of the joint angle waveforms. RESULTS: Unique and complex patterns of flexion and extension movements were observed for each joint studied. The walk had consistency of movement in the sample population in temporal and distance variables and joint movements. Variances attributable to intra- and interdog differences were similar and 1 to 2 orders of magnitude smaller than the mean Fourier coefficients from which they were calculated for all 6 joints. The number of essential Fourier coefficients required to represent the joint angle waveforms was 3 for the coxofemoral joint, 5 each for the femorotibial, scapulohumeral, cubital, and carpal joints, and 6 for the tarsal joint. CONCLUSIONS: Computer-assisted kinematic gait analysis proved to be a reliable and consistent technique for assessment of movement at the walk in dogs, and Fourier transformation was shown to be an effective tool for analysis of the kinematic data. CLINICAL RELEVANCE: The database derived from the normal sample population in this study can be used as a model of musculoskeletal function at the walk for future comparisons with disease and treatment.

Kinematic evaluation of gait in dogs with cranial cruciate ligament rupture.

OBJECTIVE: Noninvasive, computer-assisted, three-dimensional kinematic gait analysis was used to describe lameness in a chronic model of cranial cruciate ligament rupture (CCLR) in dogs. DESIGN: Hind limb lameness was evaluated prior to and at 1, 3, and 6 months after transection of the cranial cruciate ligament. ANIMALS: Seven clinically normal large dogs. PROCEDURE: Dynamic flexion and extension angles and angular velocities were calculated for the coxofemoral, femorotibial, and tarsal joints. Distance and temporal variables were determined. Essential Fourier coefficients were used to develop mean flexion extension curves for all joints and to compare changes in movement that developed with CCLR over time. RESULTS: Each joint had a characteristics pattern of flexion and extension movement that changed with CCLR. The femorotibial joint angle was more flexed throughout stance and early swing phase of stride and failed to extend in late stance. Angular velocity of the femorotibial joint was damped throughout stance phase, with extension velocity almost negligible. The coxofemoral and tarsal joint angles, in contrast to the femorotibial joint angle, were extended more during stance phase. These changes were documented as differences noted in the essential Fourier coefficients. Stride length and frequency also varied significantly after CCLR. CONCLUSIONS: Cranial cruciate ligament rupture affects movement of the coxofemoral and tarsal joints, as well as the femorotibial joint, in gait. A pattern of joint movement may be discerned in which the coxofemoral and tarsal joints compensate for the dysfunction of the femorotibial joint. CLINICAL RELEVANCE: Methods were developed that will improve objective evaluation of CCLR and its treatment in dogs.

Changes in renal function associated with treatment of hyperthyroidism in cats.

We measured glomerular filtration rate (GFR) estimated by plasma disappearance of 99mTc-labeled diethylenetriaminepentaacetic acid, serum concentrations of thyroxine (T4), creatinine, and urea nitrogen, and urine specific gravity in 13 cats with naturally acquired hyperthyroidism before and 30 days after treatment by bilateral thyroidectomy, and in a group of 11 control cats. Mean (+/- SD) serum T4 concentration decreased from a pretreatment value of 120.46 (+/- 39.21) nmol/L to a posttreatment value of 12.15 (+/- 6.26) nmol/L (P < 0.0001; reference range, 10 to 48 nmol/L). Treatment of hyperthyroidism resulted in a decrease in mean (+/- SD) glomerular filtration rate, from 2.51 (+/- 0.69) ml/kg of body weight/min to a posttreatment value of 1.40 (+/- 0.41) ml/kg/min (P < 0.0001). Mean serum creatinine concentration increased from 1.26 (+/- 0.34) mg/dl to 2.05 (+/- 0.60) mg/dl (P < 0.01). Mean serum urea nitrogen concentration increased from 26.62 (+/- 6.83) mg/dl to a mean postthyroidectomy concentration of 34.92 (+/- 8.95) mg/dl (P < 0.01). All changes were significant. Two cats developed overt renal azotemia after treatment of hyperthyroidism. Our results provide further evidence that treatment of hyperthyroidism can result in impaired renal function. In addition, our results suggest that, in some instances, thyrotoxicosis might mask underlying chronic renal insufficiency.

Characterization of baroreflex impairment in conscious dogs with pacing-induced heart failure.

Open-loop baroreflex responses were evaluated in eight conscious dogs before and during congestive heart failure to determine the effects of failure on baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance. Heart failure was induced by rapid ventricular pacing. Baroreflex function was determined by calculation of the range and gain of the open-loop stimulus-response relationships for the effect of carotid sinus pressure on blood pressure, heart rate, cardiac output, and total peripheral resistance. The range and gain of blood pressure responses were substantially reduced as early as 3 days after induction of heart failure (161 +/- 6 to 99 +/- 8 mmHg and -2.7 +/- 0.3 to -1.5 +/- 0.1, respectively) and remained depressed for the 21 days of heart failure. This depression in baroreflex control of blood pressure was associated with similar depressions in reflex range and gain for heart rate (125 +/- 9 to 78 +/- 11 beats/min and -2.05 +/- 0.2 to -1.16 +/- 0.2 beats/min, respectively) and cardiac output (1.74 +/- 0.2 to 0.46 +/- 0.2 l/min and -0.81 +/- 0.02 to -0.027 +/- 0.008 l/min, respectively). The group-averaged range and gain for reflex control of vascular resistance were not altered by heart failure. In three dogs, discontinuation of rapid ventricular pacing led to resolution of heart failure within 7 days and partial restoration of the range and gain of reflex control of blood pressure. We conclude that heart failure reversibly depresses baroreflex control of blood pressure principally through a concurrent reduction in reflex control of cardiac output, whereas reflex control of vascular resistance is not consistently affected.

Heart failure depresses endothelium-dependent responses in canine femoral artery.

Vascular responses to many physiological stresses are abnormal in heart failure. Increased peripheral resistance and a reduction in the vasodilator response to exercise and ischemia are examples of this abnormal vascular control. Such abnormal vascular control in heart failure is a result of interplay between neural, hormonal, and local vascular factors. This study was designed to test the hypothesis that a specific local mechanism, endothelium-dependent relaxation to acetylcholine (ACh), is depressed in experimental heart failure. Experiments were performed on 11 purebred beagles. Experimental heart failure was induced by rapid ventricular pacing for approximately 30 days. Femoral artery diameter was measured by sonomicrometry, and dose-response relationships to ACh, norepinephrine (NE), and nitroglycerin (NTG) were done before and after inhibition of cyclooxygenase by indomethacin. Heart failure resulted in a significant depression of ACh relaxation at all concentrations. In dogs with heart failure, indomethacin enhanced the dilation response to low concentrations of ACh. Constriction to NE and dilation to NTG were unchanged by heart failure. These data demonstrate that in the canine femoral artery endothelium-dependent dilation to ACh is depressed in experimental heart failure. Depression of endothelium-dependent vasodilation represents one local mechanism for abnormal control of the vasculature in congestive heart failure.