Feline myocardial transcriptome in health and in hypertrophic cardiomyopathy-A translational animal model for human disease.

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by primary left ventricular hypertrophy. Feline HCM closely resembles human HCM and is suggested as translational animal model for the human disease. A genetic cause is established in humans and suspected for cats, but little is known about the gene expression and pathways involved in the pathogenesis of HCM. To investigate the myocardial transcriptome changes in HCM, RNA sequencing was conducted on left ventricle (LV) and left atrium (LA) samples of healthy cats and cats with HCM (each n = 5; 20 samples). Ingenuity Pathway Analysis was used to determine functional pathways, regulators, and networks. Distinct gene expression profiles were identified in the LV and LA of the feline healthy and HCM myocardium. Analysis of differentially expressed mRNAs (>2 fold; FDR < 0.01) found chamber-specific (LV vs. LA) expression in both healthy and HCM groups, with higher transcriptional activity in the LA. Genes that contribute to the distinct structure and function of each chamber in health and HCM were identified in the regional comparison. The gene expression profiles of HCM compared to healthy hearts revealed disease related genes, including THBS4 and KLHL33 (LV), FAM177B and THRSP (LA), the latter 3 have not been reported for the myocardium so far, as the top differently expressed genes in the HCM heart. Differently expressed genes and functional pathways found in the HCM heart are associated with cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling and cardiac metabolism, with some regional differences. RhoGDI-RhoGTPase signaling, integrin and ILK signaling pathways, the LXR/RXR pathway in the LA, and the PPARα/RXRα, HIF1α and CXCR4 pathways in the LV might be of particular importance in the HCM disease process. This study identified region-specific myocardial gene transcription patterns as well as novel genes and pathways associated with HCM.

Cardiac gene activation varies between young and adult cats and in the presence of hypertrophic cardiomyopathy.

Little is known about the difference of myocardial gene transcription in young and adult cats and how transcription is further modified in cats with hypertrophic cardiomyopathy (HCM) and with left atrial (LA) thrombus formation. We hypothesized that selected factors for coagulation, endothelial activation, inflammation, and remodelling are modified with age and are activated in the hearts of cats with HCM. Left atrial and ventricular (LV) samples from 12 cats with HCM (seven without (HCMwoAT] and five with LA thrombi [HCMwAT]), and six young (YC) and six adult (AC) control cats without cardiac disease were investigated for relative expression of the following genes using quantitative polymerase chain reaction: von Willebrand factor, a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13, platelet activating factor, E- and P-selectin, intercellular and vascular adhesion molecules-1, ß2-integrin, vascular endothelial growth factor, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), heat shock protein-70, and myocyte-specific enhancer factor 2C. Significant differences in gene activation were found between YC and AC, and YC and cats with HCM. Compared to AC, MCP-1 and IL-6 were significantly higher in cats with HCM. The presence of an LA thrombus was associated with higher IL-6 expression. These results illustrate the relevance of age and/or lifestyle on gene expression in the feline heart. The gene transcription pattern found in AC hearts might predispose cats to their characteristic cardiac remodelling processes and thrombus formation if disease occurs. It further supports the involvement of inflammation, but not coagulation and endothelial activation, in HCM.

Effects of handling and storage on potassium concentration in plasma and serum samples obtained from cats.

OBJECTIVE: To compare potassium concentrations in feline plasma and serum samples analyzed promptly after collection or after 20 to 28 hours of refrigerated storage. ANIMALS: 41 cats. PROCEDURES: A venous blood sample was obtained from each cat. Aliquots were placed in 2 tubes without anticoagulant (blood was allowed to clot to derive serum) and 2 tubes with heparin (to derive plasma). One serum and 1 plasma sample were kept at room temperature and analyzed within 60 minutes after collection (baseline); the other serum and plasma samples were analyzed after 20 to 28 hours of refrigerated storage. At both time points, serum and plasma potassium concentrations were measured. RESULTS: Median baseline serum potassium concentration (4.3 mmol/L) was significantly higher than median baseline plasma potassium concentration (4.1 mmol/L). The median difference between those values was 0.4 mmol/L (95% CI, 0.2 to 0.5 mmol/L). Compared with their respective baseline measurements, the median serum plasma concentration (4.8 mmol/L) and median plasma potassium concentration (4.6 mmol/L) were higher after 20 to 28 hours of refrigeration. CLINICAL RELEVANCE: Results indicated that with regard to potassium concentration in feline blood samples, clotting or refrigerated storage for 20 to 28 hours results in a significant artifactual increase. Detection of an unexpectedly high potassium concentration in a cat may represent pseudohyperkalemia, especially if the blood sample was placed in a no-additive tube, was stored for 20 to 28 hours prior to analysis, or both.

Use of intravenous lidocaine to treat dexmedetomidine-induced bradycardia in sedated and anesthetized dogs.

OBJECTIVE: To assess cardiopulmonary function in sedated and anesthetized dogs administered intravenous (IV) dexmedetomidine and subsequently administered IV lidocaine to treat dexmedetomidine-induced bradycardia. STUDY DESIGN: Prospective, randomized, crossover experimental trial. ANIMALS: A total of six purpose-bred female Beagle dogs, weighing 9.1 ± 0.6 kg (mean ± standard deviation). METHODS: Dogs were randomly assigned to one of three treatments: dexmedetomidine (10 µg kg-1 IV) administered to conscious (treatments SED1 and SED2) or isoflurane-anesthetized dogs (end-tidal isoflurane concentration 1.19 ± 0.04%; treatment ISO). After 30 minutes, a lidocaine bolus (2 mg kg-1) IV was administered in treatments SED1 and ISO, followed 20 minutes later by a second bolus (2 mg kg-1) and a 30 minute lidocaine constant rate infusion (L-CRI) at 50 (SED1) or 100 µg kg-1 minute-1 (ISO). In SED2, lidocaine bolus and L-CRI (50 µg kg-1 minute-1) were administered 5 minutes after dexmedetomidine. Cardiopulmonary measurements were obtained after dexmedetomidine, after lidocaine bolus, during L-CRI and 30 minutes after discontinuing L-CRI. A mixed linear model was used for comparisons within treatments (p < 0.05). RESULTS: When administered after a bolus of dexmedetomidine, lidocaine bolus and L-CRI significantly increased heart rate and cardiac index, decreased mean blood pressure, systemic vascular resistance index and oxygen extraction ratio, and did not affect stroke volume index in all treatments. CONCLUSION AND CLINICAL RELEVANCE: Lidocaine was an effective treatment for dexmedetomidine-induced bradycardia in healthy research dogs.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Development of a technique for determination of pulmonary artery pulse wave velocity in horses.

Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the main PA of 10 sedated horses. The pressure waves were used to determine PWV along the PA, using the statistical phase offset method. Histological analysis of the PA was performed to investigate the presence of fibro-calcified lesions. The mean (±SD) PWV was 2.3 ± 0.7 m/s in the proximal PA trunk and 1.1 ± 0.1 m/s further distal (15 cm) in a main PA branch. The mean (±SD) of mean arterial pressures in the proximal PA trunk was 30.1 ± 5.2 mmHg, and 22.0 ± 6.0 mmHg further distal (15 cm) within the main PA branch. The mean (±SD) pulse pressure in the proximal PA trunk was 15.0 ± 4.7 mmHg, and 13.5 ± 3.3 mmHg further distal (15 cm) within the main PA branch. Moderate to severe lesions of the tunica media of the PAs were observed in seven horses, but a correlation with PWV could not be established yet. Pulmonary artery PWV may be determined in standing horses. The technique described may allow further investigation of the effect of calcification of large PAs in the pathogenesis of equine pulmonary circulatory disorders.NEW & NOTEWORTHY Pulmonary artery pulse wave velocity was determined safely in standing sedated horses. The technique described may allow further investigation of the effect of calcification of large pulmonary arteries in the pathogenesis of pulmonary circulatory disorders in horses.

Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism. Platelet Function Analyzer 100 and Plateletworks may be useful for confirming clopidogrel treatment in these cats.

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM.

Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests.

The objectives of this study were to establish feline references intervals for 3 commercial whole blood platelet function test analyzer systems: Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario, Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX). Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95% confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89) sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using flow cytometry hematology analyzer platelet counts. There were low correlations between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; ρ = 0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist using impedance platelet counts; ρ = 0.14). The PW assay percent aggregations using impedance and flow cytometric platelet counts were correlated for both ADP (ρ = 0.64) and COL (ρ = 0.64) agonists. Platelet function testing using these tests are feasible in cats, but 95% CIs are wide, so single results may be difficult to interpret. Platelet counting by impedance or flow cytometry may be used for the PW assay but are not interchangeable.

Short-term disruption of diurnal rhythms after murine myocardial infarction adversely affects long-term myocardial structure and function.

RATIONALE: Patients in intensive care units are disconnected from their natural environment. Synchrony between environmental diurnal rhythms and intracellular circadian rhythms is essential for normal organ biology; disruption causes pathology. Whether disturbing rhythms after myocardial infarction (MI) exacerbates long-term myocardial dysfunction is not known. OBJECTIVE: Short-term diurnal rhythm disruption immediately after MI impairs remodeling and adversely affects long-term cardiac structure and function in a murine model. METHODS AND RESULTS: Mice were infarcted by left anterior descending coronary artery ligation (MI model) within a 3-hour time window, randomized to either a normal diurnal or disrupted environment for 5 days, and then maintained under normal diurnal conditions. Initial infarct size was identical. Short-term diurnal disruption adversely affected body metabolism and altered early innate immune responses. In the first 5 days, crucial for scar formation, there were significant differences in cardiac myeloperoxidase, cytokines, neutrophil, and macrophage infiltration. Homozygous clock mutant mice exhibited altered infiltration after MI, consistent with circadian mechanisms underlying innate immune responses crucial for scar formation. In the proliferative phase, 1 week after MI, this led to significantly less blood vessel formation in the infarct region of disrupted mice; by day 14, echocardiography showed increased left ventricular dilation and infarct expansion. These differences continued to evolve with worse cardiac structure and function by 8 weeks after MI. CONCLUSIONS: Diurnal rhythm disruption immediately after MI impaired healing and exacerbated maladaptive cardiac remodeling. These preclinical findings suggest that disrupted diurnal rhythms such as found in modern intensive care unit environments may adversely affect long-term patient outcome.

Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats.

Novel anesthetic agents or combinations may provide superior general anesthesia for echocardiography in rodents with the potential for reduced adverse effects. This study sought to characterize the effects of 3 injectable anesthetics on left ventricular (LV) systolic function and cardiac morphology in healthy male and female rats. Rats underwent echocardiographic assessment after general anesthesia via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine and midazolam (KMI) according to a crossover Latin-square design. Blood samples for serum estradiol measurements were obtained from all females after echocardiography with each anesthetic. Rats given KMI showed superior LV systolic function with the highest values for fractional shortening (FS), ejection fraction (EF) and stroke volume, whereas heart rate was greatest with pentobarbital, followed by KMI and then KME. KME produced the greatest effects on cardiac morphology, most notably during systole, including reduced septal and posterior wall thickness and increased LV chamber dimensions and volumes. In addition, KME had the greatest cardiac-depressing effects on LV systolic function, including reduced FS, EF, and heart rate values. Compared with male rats, female rats had superior LV function with greater EF and FS values, whereas male rats showed higher heart rate. Significant negative correlations were noted between serum estradiol levels and FS and EF values in female rats receiving KME. We conclude that the combination of KMI may be a superior anesthetic for use in male and female rats undergoing echocardiography.

Transtumoral plating as a novel method for palliative limb spare and thromboembolism in a dog with a distal radial primary bone tumor.

A 7-year-old, spayed, female great Pyrenees with a primary tumor of the distal radius was treated with placement of a bone plate that spanned the tumor. The goals were palliation and prevention of pathologic fracture. This is an option for select patients with osteosarcoma.

Feasibility of percutaneous catheterization and embolization of the thoracic duct in dogs.

OBJECTIVE: To develop and determine the feasibility of a novel minimally invasive technique for percutaneous catheterization and embolization of the thoracic duct (PCETD) in dogs and to determine thoricic duct TD pressure at rest and during short-term balloon occlusion of the cranial vena cava (CrVC). ANIMALS: Fifteen 7- to 11-month-old healthy mixed-breed dogs. PROCEDURES: Efferent intestinal lymphangiography was performed, and the cisterna chyli was punctured with a trochar needle percutaneously under fluoroscopic guidance. When access was successful, a guide wire was directed into the TD through the needle and a vascular access sheath was advanced over the guide wire. Thoracic duct pressure was measured at rest and during acute balloon occlusion of the CrVC. The TD was then embolized cranial to the diaphragm with a combination of microcoils and cyanoacrylate or ethylene vinyl alcohol. RESULTS: Successful puncture of the cisterna chyli with advancement of a wire into the TD was possible in 9 of 15 dogs, but successful catheterization was possible in only 5 of 9 dogs. Acute balloon occlusion of the CrVC led to a substantial TD pressure increase in 4 of 4 dogs, and embolization of the TD was successful in 4 of 4 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: PCETD can successfully be performed in healthy dogs; however, this minimally invasive technique cannot currently be recommended for routine treatment of chylothorax, in part because of the technically demanding nature of the procedure. An increase in jugular venous pressure led to an increase in TD pressure, potentially predisposing some dogs to developing chylothorax.

Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy.

OBJECTIVE: To identify a causative mutation for dilated cardiomyopathy (DCM) in Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to be associated with familial DCM in humans. ANIMALS: 5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died. PROCEDURES: RNA was extracted from frozen ventricular myocardial samples from each dog, and first-strand cDNA was synthesized via reverse transcription, followed by PCR amplification with gene-specific primers. Ten cardiac genes were analyzed: cardiac actin, α-actinin, α-tropomyosin, ß-myosin heavy chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin-cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and the published canine genome were compared. RESULTS: None of the coding sequences yielded a common causative mutation among all Doberman Pinscher samples. However, 3 variants were identified in the α-actinin gene in the DCM-affected Doberman Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers, resulted in an amino acid change in the rod-forming triple coiled-coil domain. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations in the coding regions of several genes associated with DCM in humans did not appear to consistently account for DCM in Doberman Pinschers. However, an α-actinin variant was detected in some Doberman Pinschers that may contribute to the development of DCM given its potential effect on the structure of this protein. Investigation of additional candidate gene coding and noncoding regions and further evaluation of the role of α-actinin in development of DCM in Doberman Pinschers are warranted.

Comparison of computed tomographic and radiographic popliteal lymphangiography in normal dogs.

OBJECTIVE: To (1) describe computed tomographic (CT) popliteal lymphangiography; (2) compare the number of thoracic duct (TD) branches detected by CT and by radiography after popliteal lymphangiography; and (3) to compare the number of branches detected after left and right popliteal lymphangiography. STUDY DESIGN: Experimental study. ANIMALS: Adult dogs (n=6). METHODS: A randomly selected popliteal lymph node was percutaneously injected with 12 L iodinated contrast medium through a 25-g butterfly catheter over 4-5 minutes. Lateral and ventrodorsal (VD) thoracic radiograph projections and thoracic CT were performed. The procedure was repeated using the contralateral lymph node after a 48-72 hours washout period. RESULTS: One dog had TD branches visible on CT but not on radiographs. A significantly greater number of TD branches were observed with CT popliteal lymphangiography compared with lateral and VD radiographic popliteal lymphangiography (P=.003 and P<.001, respectively). The number of visible TD branches observed between the 6th thoracic and 1st lumbar vertebrae were not significantly different in these dogs (P=.146). A significant difference in number of TD branches observed was not found after left or right popliteal lymph node injection (P=.097). CONCLUSIONS: CT popliteal lymphangiography consistently identified a greater number of TD branches when compared with radiographic popliteal lymphangiography. Injection of either popliteal lymph node resulted in the same number of TD branches being observed.

Cranial vena caval thrombosis associated with endocardial pacing leads in three dogs.

Three dogs were examined several years following implantation of transvenous, single-lead, endocardial, right-ventricular permanent pacing systems for signs consistent with cranial vena caval syndrome. Angiograms performed in all dogs revealed filling defects within the cranial vena cava and, in some instances, intracardiac filling defects. Medical therapy was instituted in two dogs, with one surviving several weeks. One dog underwent surgery to address intra-cardiac thrombosis but did not survive the immediate postoperative period. Postmortem examinations were performed in two dogs and confirmed cranial vena caval and intracardiac thrombosis. Cranial vena caval thrombosis associated with transvenous pacing leads appears to carry significant morbidity and mortality.

Perceptions and priorities of owners of dogs with heart disease regarding quality versus quantity of life for their pets.

OBJECTIVE: To describe the relative importance of pets' quality versus quantity of life among owners of dogs with heart disease. DESIGN: Prospective questionnaire-based clinical study. SAMPLE POPULATION: Owners of 201 dogs with heart disease. PROCEDURES: Owners each completed a questionnaire that was designed to ascertain the relative importance of quality versus quantity of life for their pet and to assess the owners' willingness to trade survival time for quality of life, if that were possible. Analyses were performed to evaluate factors associated with owner willingness to trade time for quality of life. RESULTS: Most owners (170/197 [86%]) were willing to trade survival time for quality of life for their heart disease-affected dogs; of those owners, 88 (52%) were willing to trade 6 months. Owners were highly concerned with detection of perceived pet suffering and their pet's ability to interact with them. Owners whose pets had respiratory difficulty or fainting episodes and were treated on an outpatient basis had a greater willingness to trade survival time than owners of dogs that were treated on an emergency basis. Among owners willing to trade time for quality of life, younger owners and those whose pets had fainting episodes were willing to trade the most amount of time. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that quality of life is highly important to owners of dogs with heart disease. Owners' priorities partly depend on owner age and the pet's clinical circumstances; ongoing client-veterinarian communication is important to optimize treatment success as perceived by owners.

Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs.

OBJECTIVE: To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS: After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.

Plasma big endothelin-1, atrial natriuretic peptide, aldosterone, and norepinephrine concentrations in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. HYPOTHESIS: We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. ANIMALS: Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. METHODS: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. RESULTS: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis.