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.

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.

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.

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.