Comparison of two echocardiographic views for evaluating the right pulmonary artery distensibility index in dogs.

Echocardiographic evaluation of the right pulmonary artery distensibility index (RPAD index) was recently described as a valuable method for early detection and severity evaluation of pulmonary arterial hypertension in dogs. RPAD index is calculated as the percentage change in diameter of the right pulmonary artery (RPA) between systole and diastole, obtained by M-mode echocardiography from the right parasternal long axis view. The aim of this study was to compare the RPAD index obtained by 2 different echocardiographic views in dogs. The study design was a prospective, multicenter, observational study. Forty-five clientowned dogs from different breeds were included: 31 dogs with heart disease and 14 healthy dogs. Two different right parasternal views, long axis (RPLA) and short axis (RPSA), were used to measure the RPAD index. From the RPLA view (method 1) and RPSA view (method 2) a short axis and a long axis image were respectively optimized for the right pulmonary artery. The RPAD index was calculated by M-mode as the percentage change in diameter of the right pulmonary artery: [(systolic diameter - diastolic diameter)/ systolic diameter]*100. Measurements were done off-line as an average of 5 consecutive cardiac cycles by a single investigator blinded to the dogs’ diagnosis. A Pearson and a Bland-Altman test were used to assess correlation and agreement between the 2 methods, respectively. Intra- and inter-observer measurement variability was quantified by average coefficient of variation (CV). Level of significance was set at P < 0.05. M-mode evaluation of the RPAD index was satisfactorily obtained by both methods in all dogs. Pearson test showed a strong positive linear correlation between the values of RPAD index obtained from both methods (r2 = 0.9346, P < 0.0001). Bland-Altman test showed a good agreement between the 2 methods in estimating RPAD index (bias = 0.51%, SD = 2.96%, 95% limits of agreement = 5.30, 6.33%). The mean difference between the 2 methods was 0.51% (95% confidence interval = 0.35; 1.35). Intra- and inter-observer measurement variability was clinically acceptable (CV<10%).The study showed a good agreement between short axis and long axis M-mode evaluation of RPA. Both methods can be used interchangeably to evaluate RPAD index. Further studies are needed to evaluate the RPAD index in a larger population of healthy dogs and the diagnostic and prognostic role of this echocardiographic parameter in dogs with different types of pulmonary hypertension

Statins, fibrates, and venous thromboembolism: a meta-analysis.

Aims The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. Methods and results MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Three randomized controlled trials (RCTs), three cohort, and eight case\u2013control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66\u20130.99, random-effect model)]. There was a very high heterogeneity among the studies (I2 > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23\u20132.02), without heterogeneity (I2 = 0%). Data on other lipid-lowering drugs were lacking. Conclusion This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted

Differential ABC transporter gene expression in adult Dirofilaria immitis males and females following in vitro treatment with ivermectin, doxycycline or a combination of both

BACKGROUND: Combination doxycycline/macrocyclic lactone (ML) protocols have been shown to provide a more rapid adulticidal and microfilaricidal effect than either MLs or doxycycline alone, although female worms were reported to have a higher tolerance to treatments compared to male worms. The present study aimed to evaluate how ABC transporters may be involved in the synergic effect of the combination treatment. Adult worms of D. immitis were treated in vitro for 24 hours with doxycycline (DOXY), ivermectin (IVM) and a combination of both, and changes in the modulation of ABC transporter genes were measured. Levels of doxycycline inside different treatment media, post-treatment, were determined through HPLC analysis. RESULTS: Quantitative RT-PCR analysis showed the presence of changes in the modulation of ABC transporter genes evaluated in this study. In particular, in female worms, the combination treatment induced a substantial increase in gene expressions, especially of Dim-pgp-10 and Dim-haf-4; whereas in male worms, the greatest increase in gene expression was observed for Dim-pgp-10 and Dim-pgp-11 when treated with DMSO\u2009+\u2009IVM and DMSO\u2009+\u2009DOXY/IVM. HPLC analysis of the DOXY concentrations in the media after in vitro treatments of male worms showed a slight difference between the DMSO\u2009+\u2009DOXY samples and the combination (DMSO\u2009+\u2009DOXY\u2009+\u2009IVM), while no difference was observed among females. CONCLUSIONS: Further studies are required to explain whether the modulation of cellular efflux plays a role, even partially, in the adulticide effect of doxycycline/macrocyclic lactone combinations in heartworm-infected dogs. To the authors' knowledge, this is the first study to evaluate P-gp expression in adult D. immitis

Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH