Echocardiographic predictors of first onset of atrial fibrillation in dogs with myxomatous mitral valve disease

Background: Atrial fibrillation (AF) occurs in dogs with myxomatous mitral valve disease (MMVD) as a consequence of left atrial (LA) dilatation, and it affects survival and quality of life. Objectives: To evaluate the usefulness of echocardiography in predicting the first occurrence of AF in dogs with MMVD. Animals: Forty-four client-owned dogs with MMVD, 22 dogs that developed AF, and 22 dogs that maintained sinus rhythm. Methods: Retrospective observational study. Medical databases were reviewed for dogs that developed AF during the year after diagnosis of MMVD (AF group). The last echocardiographic examination obtained while still in sinus rhythm was used to derive selected variables. For each dog with AF, a control dog matched for body weight, class of heart failure, and LA dimension was selected. Echocardiographic results including LA volumes and LA speckle tracking echocardiography (STE)-derived variables were measured. Results: Among the tested echocardiographic variables, only LA diameter (P =.03) and left ventricular internal diameter in diastole (P =.03) differed significantly between groups, whereas body weight-indexed variables of cardiac dimension as well as LA volumes and volume-derived functional variables were not different. Among the STE-derived variables, peak atrial longitudinal strain (PALS) results differed significantly between the AF group (23.8% \ub1 8.6%) and the control group (30.5% \ub1 9.6%; P =.03). A value of PALS 6428% predicted AF occurrence with sensitivity and specificity of 0.80 and 0.65, respectively. Conclusions and Clinical Importance: Absolute cardiac diameters and LA STE (in particular, PALS) are useful echocardiographic predictors for the development of AF in dogs with MMVD

Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study

Background: Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives: To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals: Forty client-owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods: Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results: Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P =.04, P =.002, and P =.003, respectively) and E-point-to-septal separation normalized to body weight (EPSSn) and trans-mitral E wave velocity (E max; P <.001 and P =.025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P <.001, P =.004, P =.002, and P =.009, respectively) and significantly decreased left ventricular end-diastolic volume index, and normalized systolic diameter and EPSSn (P =.03, P =.03, and P =.001, respectively) were found. Conclusions and Clinical Importance: Hypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs

Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study.

Background: Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives: To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals: Forty client-owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods: Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results: Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P =.04, P =.002, and P =.003, respectively) and E-point-to-septal separation normalized to body weight (EPSSn) and trans-mitral E wave velocity (E max; P <.001 and P =.025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P <.001, P =.004, P =.002, and P =.009, respectively) and significantly decreased left ventricular end-diastolic volume index, and normalized systolic diameter and EPSSn (P =.03, P =.03, and P =.001, respectively) were found. Conclusions and Clinical Importance: Hypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs

Transient myocardial thickening: a retrospective analysis on etiological, clinical, laboratory, therapeutic, and outcome findings in 27 cats

Introduction/objective: Transient myocardial thickening (TMT) in cats is a poorly characterized clinical entity. Therefore, this study aimed to provide descriptions of additional cats diagnosed with this clinical phenomenon.Animals, materials, and methods: For this multicenter observational retrospective study, cats diagnosed with TMT were searched in three medical databases. TMT was defined for cats with at least two echocardiograms showing an increased end diastolic left ventricular wall thickness (LVWTd; i.e.>= 6 mm) at presentation and subsequent echocardiographic normalization (i.e. LVWTd <5.5 mm). Signalment, history, clinical, laboratory, therapeutic, and outcome data were retrieved. Results: 27 cats were included. The median age was 3 years. In 9/27 cats, an antecedent event was documented. At admission, 27/27 cats had evidence of myocardial injury (median value of cardiac troponin I 5.5 ng/mL), 25/27 cats had congestive heart failure, 13/27 cats had hypothermia, 8/27 cats had systemic hypotension, 7/27 cats had bradycardia, and 7/27 cats had electrocardiographic evidence of an arrhythmia. The median LVWTd was 6.4 mm. A potential cause of myocardial injury was identified in 14/27 cats. The median time from diagnosi

Whole-body glucose oxidation rate during prolonged exercise in type 1 diabetic patients under usual life conditions

Objective Fuel oxidation during exercise was studied in type 1 insulin-dependent (T1DM) patients mainly under quite constant insulin and glycemia; these protocols, however, likely do not reflect patients' usual metabolic conditions. The glucose oxidation rate (GLUox) in T1DM patients under usual life conditions was thus investigated during prolonged exercise (3-h) and its behavior was described mathematically. Materials/Methods Whole-body GLUox was determined in eight T1DM patients (4/8 M; aged 35-59 years) and eight well-matched healthy subjects. Venous blood was drawn prior to and every 30 min until the end of exercise; glycemia, insulin, cortisol, and growth hormone concentrations were determined. Oxygen consumption, carbon dioxide production, and ventilation were measured at rest and thereafter every 30 min of the exercise. To prevent hypoglycemia, patients were given fruit fudge (93% sucrose) prior to / during exercise. Results Insulin concentration and glycemia were significantly higher in patients across the entire exercise period (group effect, p < 0.001 for both). GLUox decreased significantly with increasing exercise duration (time effect, p < 0.001), but no significant difference was detected between the two groups (group effect, p = NS). GLUox, expressed as the percentage of the starting value, was described by an exponential function showing a time constant of 90 min (n = 96; mean corrected R2 = 0.666). Conclusions GLUox in T1DM patients was not significantly different from the rate observed in the control subjects. The function describing the time course of GLUox may be useful to correct an estimated GLUox for the duration of exercise and help T1DM patients avoiding exercise-induced glycemic imbalances

Plasmatic Dimethylarginines in Dogs With Myxomatous Mitral Valve Disease

Plasmatic dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are considered biomarkers of endothelial and renal dysfunction, respectively, in humans. We hypothesize that plasmatic concentration of dimethylarginines in dogs with myxomatous mitral valve disease (MMVD) is influenced by heart disease stage. Eighty-five client-owned dogs with MMVD, including 39, 19, and 27 dogs in ACVIM stages B1, B2, and C+D, respectively, and a control group of 11 clinically healthy dogs were enrolled. A prospective, multicentric, case-control study was performed. Each dog underwent a complete clinical examination, arterial blood pressure measurement, thoracic radiography, six-lead standard electrocardiogram, transthoracic echocardiography, CBC, biochemical profile, and urinalysis. Plasmatic concentration of dimethylarginines was determined through high-performance liquid chromatography coupled with tandem mass spectrometry. Median ADMA was significantly increased in dogs of group C+D (2.5 μmol/L [2.1–3.0]) compared to those of group B1 (1.8 μmol/L [1.6–2.3]; p &lt; 0.001) and healthy dogs (1.9 μmol/L [1.7–2.3]; p = 0.02). Median SDMA was significantly increased in dogs of group C+D (0.7 μmol/L [0.5–0.9]) compared to those of groups B1 (0.4 μmol/L [0.3–0.5]; p &lt; 0.001), B2 (0.4 μmol/L [0.3–0.6]; p &lt; 0.01), and the control group (0.4 μmol/L [0.35–0.45]; p = 0.001). In the final multivariable analysis, ADMA and SDMA were significantly associated with left atrium to aorta ratio (p &lt; 0.001), and creatinine (p &lt; 0.001), respectively. Increased plasmatic concentrations of dimethylarginines suggest a possible role as biomarkers of disease severity in dogs with decompensated MMVD

Red Blood Cell Distribution Width, Hematology, and Serum Biochemistry in Dogs with Echocardiographically Estimated Precapillary and Postcapillary Pulmonary Arterial Hypertension

Background: Red blood cell distribution width (RDW) is a quantitative measurement of anisocytosis. RDW has prognostic value in humans with different cardiovascular and systemic disorders, but few studies have investigated this biomarker in dogs. Objectives: To compare the RDW in dogs with precapillary and postcapillary pulmonary hypertension (PH) and a control population of dogs and to correlate RDW with demographic, echocardiographic, and laboratory variables. Animals: One hundred and twenty-seven client-owned dogs including 19 healthy dogs, 82 dogs with myxomatous mitral valve disease (50 dogs without PH and 32 dogs with postcapillary PH), and 26 dogs with precapillary PH. Methods: Prospective study. Dogs were allocated to groups according to clinical and echocardiographic evaluation. RDW and selected laboratory and echocardiographic variables were compared among dog groups. Associations between RDW and demographic, laboratory, and echocardiographic variables were analyzed using correlation and multiple regression analysis. Results: Median RDW in dogs with precapillary PH (13.8%, interquartile range 13.2\ue2\u80\u9314.9%) and postcapillary PH (13.7, 13.2\ue2\u80\u9314.7%) was significantly increased compared to healthy dogs (13.3, 12.3\ue2\u80\u9313.7%; P &lt;.05 for both comparisons), but only dogs with severe PH had significantly increased RDW compared to dogs without PH (P &lt;.05). Peak tricuspid regurgitation pressure gradient was significantly associated with increased RDW (rho = 0.263, P =.007). Serum urea concentration, hematocrit, age, and white blood cell number were significantly associated with RDW in the multivariate analysis. Conclusions and Clinical Importance: Underlying pathophysiologic processes associated with PH instead of severity of PH are likely responsible for increased RDW in dogs with PH

Loss of full length CtBP1 expression enhances the invasive potential of human melanoma

BACKGROUND: The C-terminal binding protein 1 (CtBP1) is a known co-repressor of gene transcription. We recently revealed that CtBP1 expression is lost in melanoma cells and melanoma inhibitory activity (MIA) expression is subsequently increased. The present study was performed to evaluate a more general role of CtBP1 in human melanoma and identify further CtBP1-regulated target genes. METHODS: Sequence analysis and expression profile of CtBP1 in melanoma cell lines were done by PCR. Boyden Chamber assays and co-immunoprecipitation were performed to investigate the functional role of CtBP1. Gene expression analysis and micro array data were used to define target genes. RESULTS: Interestingly, we detected an alternative splice product of CtBP1 with unknown function whose expression is induced at reduction of full length CtBP1. Overexpression of full length CtBP1 in melanoma cells had no effect on cell proliferation but did influence cell migration and invasiveness. To understand the effect of CtBP1 we identified putative LEF/TCF target genes found to be strongly expressed in melanoma using DNA microarray analysis. We focused on fourteen genes not previously associated with melanoma. Detailed analysis revealed that most of these were known to be involved in tumor metastasis. Eleven genes had expression profiles associated with melanoma cell invasiveness. CONCLUSION: In summary, this study revealed that reduction of CtBP1 expression is correlated with migratory, invasive potential of melanoma cells

Re-examination of siRNA specificity questions role of PICH and Tao1 in the spindle checkpoint and identifies Mad2 as a sensitive target for small RNAs

The DNA-dependent adenosine triphosphatase (ATPase) Plk1-interacting checkpoint helicase (PICH) has recently been implicated in spindle checkpoint (SAC) signaling (Baumann et al., Cell 128(1):101–114, 2007). Depletion of PICH by siRNA abolished the SAC and resulted in an apparently selective loss of Mad2 from kinetochores, suggesting a role for PICH in the regulation of the Mad1–Mad2 interaction. An apparent rescue of SAC functionality by overexpression of PICH in PICH-depleted cells initially seemed to confirm a role for PICH in the SAC. However, we have subsequently discovered that all PICH-directed siRNA oligonucleotides that abolish the SAC also reduce Mad2 mRNA and protein expression. This reduction is functionally significant, as PICH siRNA does not abolish SAC activity in a cell line that harbors a bacterial artificial chromosome driving the expression of murine Mad2. Moreover, we identified several siRNA duplexes that effectively deplete PICH but do not significantly affect SAC functionality or Mad2 abundance or localization. Finally, we discovered that the ability of overexpressed PICH to restore SAC activity in PICH-depleted cells depends on sequestration of the mitotic kinase Plk1 rather than ATPase activity of PICH, pointing to an underlying mechanism of “bypass suppression.” In support of this view, depletion or inhibition of Plk1 also rescued SAC activity in cells harboring low levels of Mad2. This observation suggests that a reduction of Plk1 activity partially compensates for reduced Mad2 levels and argues that Plk1 normally reduces the strength of SAC signaling. Collectively, our results question the role of PICH in the SAC and instead identify Mad2 as a sensitive off target for small RNA duplexes. In support of the latter conclusion, our evidence suggests that an off-target effect on Mad2 may also contribute to explain the apparent role of the Tao1 kinase in SAC signaling (Draviam et al., Nat Cell Biol 9(5):556–564, 2007)