Sildenafil-induced priapism in a dog : an unusual case report.

BACKGROUND: Priapism is defined as erection that lasts for more than 4 h without sexual stimulation. There are various causes of priapism, but there are no reports of sildenafil-induced priapism in dogs. In human medicine, there were no pre-marketing reports of priapism caused by sildenafil, but post-marketing surveillance has shown that it is rare. In cases of pulmonary hypertension in dogs, sildenafil is the first-line drug of choice for symptomatic relief. CASE PRESENTATION: An 11-year-old neutered male Maltese dog that presented with tachypnea and cough was diagnosed with myxomatous mitral valve disease, American College of Veterinary Internal Medicine (ACVIM) stage C, and was treated medically. Eighteen months after the diagnosis, severe pulmonary hypertension occurred due to left heart disease. At 20 months postdiagnosis, pleural effusion occurred, and sildenafil (2 mg/kg twice daily) was added to the existing treatment. Two weeks later, the dyspnea recurred, confirming pleural fluid recurrence, and sildenafil was increased to 2 mg/kg thrice daily. One day later, the patient developed persistent erections and penile pain. Penile amputation and urethrostomy were recommended but were refused; therefore, analgesia and palliative care were provided. The patient died of acute dyspnea 22 months after the first presentation, with no specific priapism recurrence at the time of death. CONCLUSION: To the best of our knowledge, this is the first report of sildenafil-induced priapism in a dog with pulmonary hypertension.

Retrospective analysis of dogs and cats with a mixed form of pulmonary hypertension and suspected pulmonary capillary hemangiomatosis in comparison to animals with predomination of precapillary pulmonary hypertension.

Background: Pulmonary capillary hemangiomatosis (PCH) is an idiopathic disease with the anomalous proliferation of a small capillary-like vessel in the pulmonary tissue, which can lead to a severe form of PH. There are only several cases of PCH described in veterinary literature: 27 cases in dogs and 2 cases in cats. In veterinary medicine, PH is mostly recognized as a consequence of left heart failure as a progression of the postcapillary PH to the precapillary form. PCH is mostly described as a primary disease, but resistant postcapillary PH with the high possibility of pulmonary edema raises speculation that PCH could be a secondary malformation to the left heart disease. Aim: Discover the features associated with the shift between left- and right-sided heart disease in the context of PH development. Methods: Retrospective analysis of materials from cats and dogs with histological markers of PCH (sPCH) versus those with right heart failure (RHF). Results: Animals with histological and immunohistochemistry markers of PCH had a previous history of disease with left heart volume overload. There were no differences between the groups in radiography and gross pathology. Histologically, pulmonary fibrosis and arteriopathy could be found in RHF; in sPCH-a duplication of capillaries in alveolar septa and bizarre proliferation in surrounding structures. Conclusion: PCH could be a secondary pattern of vascular remodeling due to volume overload.

Platelet hyperresponsiveness and increased platelet-neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. HYPOTHESIS: Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation. ANIMALS: Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. METHODS: Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. RESULTS: Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. CONCLUSION AND CLINICAL IMPORTANCE: Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.

Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

OBJECTIVE: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. DESIGN: Multicenter, retrospective, case-control study from 2017 to 2021. SETTING: Private referral center and veterinary teaching hospital. ANIMALS: One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI] = 0.90 [0.84-0.95], P < 0.0001) and PHS10 (AUC [95% CI] = 0.89 [0.81-0.97], P < 0.0001). PHS8 ≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10 ≥ 3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC] = 0.74 [95% CI: 0.66-0.80], n = 135). CONCLUSIONS: Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Perivascular inflammatory cells and their association with pulmonary arterial remodelling in dogs with pulmonary hypertension due to myxomatous mitral valve disease.

Pulmonary hypertension (PH), an increase in pulmonary arterial pressure (PAP), may occur in dogs affected with myxomatous mitral valve disease (MMVD). Recent studies suggest that an accumulation of perivascular inflammatory cells may be involved with medial thickening which is a sign of the pulmonary artery remodelling in PH. The aim of this study was to characterise perivascular inflammatory cells in the surrounding pulmonary arteries of dogs with PH due to MMVD compared to MMVD dogs and healthy control dogs. Nineteen lung samples were collected from cadavers of small-breed dogs (control n = 5; MMVD n = 7; MMVD + PH n = 7). Toluidine blue stain and multiple IHC targeting α-SMA, vWF, CD20, CD68 and CD3 was performed to examine intimal and medial thickening, assess muscularisation of the small pulmonary arteries and characterise perivascular leucocytes. Medial thickening without intimal thickening of pulmonary arteries and muscularisation of normally non-muscularised small pulmonary arteries was observed in the MMVD and MMVD + PH groups compared with the control group. The perivascular numbers of B lymphocytes, T lymphocytes and macrophages was significantly increased in the MMVD + PH group compared with the MMVD and control groups. In contrast, the perivascular number of mast cells was significantly higher in the MMVD group compared with the MMVD + PH and control groups. This study suggested that pulmonary artery remodelling as medial thickening and muscularisation of the normally non-muscular small pulmonary arteries is accompanied by the accumulation of perivascular inflammatory cells.

Prognostic value of pulmonary vascular resistance estimated by echocardiography in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Progression to combined post- and pre-capillary pulmonary hypertension (PH) provides prognostic information in human patients with post-capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. OBJECTIVES: To evaluate the prognostic value of PVRecho in dogs with MMVD. ANIMALS: Fifty-four dogs with MMVD and detectable tricuspid regurgitation. METHODS: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity-time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac-related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan-Meier curves classified by PVRecho tertiles were made and compared using log-rank tests to evaluate the influence of PVRecho on all-cause mortality and cardiac-related death. RESULTS: The median follow-up time was 579 days. Forty-one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1-1.3] and 2.1 [1.6-3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. CONCLUSIONS AND CLINICAL IMPORTANCE: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation.

Effect of sage (Salvia officinalis L.) extract in antioxidant status and intestinal morphology of pulmonary hypertensive chickens.

OBJECTIVES: The effects of dietary sage on the growth performance, antioxidant status, intestinal mucosa morphology, and pulmonary hypertensive response were investigated in broiler chickens with pulmonary hypertension. METHODS: Chicks (Ross 308) were reared under cold stress for 35 days and treated with 0.05% vitamin C (positive control) and 0 (control), 0.1 or 0.2% sage extracts, then performance, oxidant and antioxidant status, and intestinal morphology were evaluated. RESULTS: The index of pulmonary hypertension (RV:TV) was decreased, and weight gain (days 22-35) was increased in all treatments (except for sage 0.1%) compared with control (P < 0.05). Lipid peroxidation was decreased, whereas the activity of antioxidant enzymes (GPX, CAT, and SOD) was increased in the sage 0.2% group compared with control (P < 0.05). In the lung, SOD, CAT, and GPX transcripts were decreased in the sage 0.2% group compared with control (P < 0.05). In the right ventricle of the heart, SOD and CAT transcripts were increased in the sage 0.2% group compared with other groups of chickens, whereas GPX transcript was decreased (P < 0.05). The jejunal villus length in the chickens fed sage was significantly lower than in control (P < 0.05). The ileal villus width, villus surface area, and lamina proporia thickness in the chickens fed sage (0.2%) were increased compared with control (P < 0.05). CONCLUSIONS: Dietary supplementation of sage (0.2%) could modulate pulmonary hypertensive response, improve antioxidant status (enzymatic activity), intestinal morphometry, and absorptive surface in the broiler chickens.

Caudal pulmonary artery to vein ratio on radiography can predict pulmonary hypertension in dogs with mitral regurgitation.

Pulmonary hypertension (PH) is an important predictor of poor outcomes in dogs with mitral regurgitation (MR). The feasibility of radiography to predict PH in dogs with MR is unknown. This retrospective, observational, and analytic study aimed to identify a radiographic parameter to predict PH in dogs with MR. A total of 302 dogs diagnosed with MR on echocardiography were enrolled. Medical record and radiographic findings such as the size of the main pulmonary artery, left atrium, left ventricle, and right chamber, and cranial and caudal pulmonary arteries and veins were evaluated according to the presence of PH. The diameters of the cranial and caudal pulmonary vessels were compared to the fourth rib and the ninth rib, respectively, and the ratio of the pulmonary artery to the corresponding vein (CdPA/CdPV) was calculated. Pulmonary hypertension was diagnosed in 77 dogs (25.5%) and the prevalence of PH increased with MR grade. The CdPA/CdPV was significantly higher (P < 0.001) in the presence of PH. Multivariate analysis showed that the CdPA/CdPV was the only independent radiographic parameter that had a significant association with PH in dogs with MR (P = 0.028). The cut-off value of the CdPA/CdPV = 1.10 showed 90.6% specificity and 31.1% sensitivity for detecting PH in dogs with MR. In dogs with MR, PH can be predicted with high specificity when the caudal pulmonary artery is 1.1 times larger than the corresponding vein on radiographs.

No evidence of pulmonary hypertension revealed in an echographic evaluation of right-sided hemodynamics in hyperthyroid cats.

OBJECTIVES: Hyperthyroidism is a common endocrinopathy affecting middle-aged to elderly cats, with multisystemic repercussions. Hyperthyroid humans show decreased lung compliance and increased cardiac output with subsequent left heart failure leading to pulmonary capillary congestion. Prognosis worsens with the development of increased pulmonary vascular pressures (ie, pulmonary hypertension [PH]) in hyperthyroid humans. The effect of excess thyroid hormone concentration on pulmonary arterial hemodynamics is unknown in cats. Assessing pulmonary vascular pressures in veterinary medicine relies heavily on echocardiographic measurements performed at the level of the heart and pulmonary trunk. This study investigated right-sided cardiac and pulmonary arterial hemodynamics in hyperthyroid cats using echocardiography. METHODS: Echocardiographic examinations of hyperthyroid cats identified through a bi-institutional database search were reviewed for the determination of systolic pulmonary arterial pressure (PAP) and 20 other metrics. Values were compared with those of a healthy cat group using non-parametric statistical analyses. RESULTS: Systolic PAP could not be determined in 23/26 hyperthyroid and 13/14 healthy cats owing to unmeasurable tricuspid regurgitation flow velocity. Hyperthyroid cats were roughly twice as old (P <0.001) and had 2-4-fold higher respiratory rates (P <0.001) than healthy cats. Hyperthyroid cats showed an increase in acceleration time-to-ejection time ratio of pulmonary flow (1.4-fold, P = 0.001), pulmonary artery velocity time integral (1.2-1.6-fold, P = 0.001), maximal pulmonary velocity (1.3-1.7-fold, P = 0.002), stroke volume (1.5-fold, P = 0.001) and cardiac output (1.6-fold, P <0.001) vs healthy cats. None of the other echocardiographic metrics reached statistical significance. CONCLUSIONS AND RELEVANCE: Systolic PAP estimation proved unsuitable as a sole measurement for the assessment of PH in hyperthyroid cats owing to the frequent inability to interrogate tricuspid regurgitant flow velocity. Hyperthyroid cats have altered echocardiographic measures of pulmonary hemodynamics dissimilar to those reported in hyperthyroid humans. Differential effects of thyrotoxic cardiomyopathy on ventricular systolic function may underlie species differences.

Feline pulmonary hypertension: are we overlooking an important comorbidity?

Pulmonary hypertension (PH) is a potential complication in many disease states, yet it has been largely overlooked in feline medicine. Recently, increased awareness of potential underlying causes has led to a wider understanding of the disease process in humans, with a focus on tailoring therapy to include specific treatment of the underlying etiology. Most of these treatments are not yet available in veterinary medicine, but as they move from the human to the veterinary field, it would be beneficial to better understand the forms of PH encountered in different species. Recently, diagnosis and classification of PH in dogs has been the focus of an American College of Veterinary Internal Medicine consensus statement, yet this condition has received little attention in cats. It is therefore our intention to raise awareness of this condition in cats and to propose a classification system for the types of PH seen in feline patients. As new medications are developed for the treatment of PH, it is important to recognize which forms of PH are seen in feline patients and understand the etiology of the disease. There are many reports of PH (or suspected PH based on echocardiographic assessment) in cats. In this review, we highlight the large number of conditions, and different etiologies, that are associated with PH. Improving understanding of this condition will bring us closer to being able to investigate the benefits of potential new diagnostics and therapies as they become available.

Pre- and postcapillary pulmonary hypertension in dogs: Circulating biomarkers.

Background: Pulmonary hypertension (PH) in dogs is a syndrome that could be primary or secondary due to pulmonary disease, pulmonary thromboembolism, heartworm disease, and heart failure. Due to the inability of right heart catheterization in veterinary patients, there is a lack of differential criteria between PH forms. In some acute cases, it is impossible to provide a full EchoCG or catheterization study. In this situation, circulating markers may be useful to discover the possible mechanism of PH form and provide specific therapy. Aim: Following all previous data in human and veterinary studies, we assumed that plasm concentration of serotonin, endothelin-1 (ET-1), and vascular endothelial growth factor D (VEGF-D) would show a predominance in affected part of pulmonary circulation. Methods: We studied 59 small-breed dogs of different sexes and ages. Groups were formed according to a primary pathology: healthy dogs (n = 8); dogs with myxomatous mitral valve disease (MMVD) and postcapillary PH (PostPH, n = 23); dogs with MMVD and precapillary PH (PrePH, n = 28). Animals in the study were diagnosed with the primary disease by standard echocardiographic methods and algorithms. Blood samples were collected at the moment of presentation and frozen in a -80°C fridge. For biochemistry analysis, we used species-specific ELISA kits, provided by Cloud-Clone Corp. (USA). The tests were provided by the means of Almazov National Medical Research Center, IEM laboratory. Results: Dogs with EchoCG-proved PostPH had a higher concentration of VEGF-D in comparison to control and PrePH (р <0.001, for both). There was no difference between the control and PrePH groups (р >0.05). ET-1 was higher in PrePH in comparison to PostPH and control dogs (р <0.001, for both). In addition, there was no difference between the control and PostPH groups (р >0.05). Serotonin concertation did not have a difference between controls and PostPH. However, it was higher in PrePH than in control (р <0.033) and PostPH group (р <0.006). Receiver operating curve analysis showed that plasma concentrations of ET-1 (0.99) and VEGF-D (0.92) had high effectiveness in the differentiation of PostPH and PrePH. Conclusion: This study showed a correlation between circulating biomarkers (serotonin, ET-1, and VEGF-D). We found a connection between ET-1 and right-sided heart failure as well as VEGF-D and left heart failure in the PH context.

Preparation of polyclonal antibody against phosphatidylethanolamine binding protein 1 recombinant protein and its functional verification in pulmonary hypertension syndrome in broilers.

Pulmonary hypertension syndrome (PHS) is a disease that is difficult to overcome for fast-growing broilers. It causes pulmonary vascular remodeling and ascites in broilers. As a classical inhibitor of cancer metastasis, phosphatidylethanolamine binding protein 1 (PEBP1) regulates angiogenesis in the process of tumor metastasis through multiple signal pathways. However, whether PEBP1 can regulate pulmonary artery remodeling in broilers with PHS has not been reported. This study constructed the prokaryotic expression vector of [PEBP1]-pET32a by genetic engineering technology, the recombinant PEBP1 protein was expressed in large quantities, and the PEBP1 polyclonal antibody was prepared by immunizing rabbits with the recombinant PEBP1 protein. Western blot and immunofluorescence results showed that PEBP1 was expressed in many kinds of animal tissues. However, due to the species specificity of polyclonal antibodies, the expression level of PEBP1 protein in broilers and ducks with high homology was significantly higher than that in other species of animals. More interestingly, we found that the expression of PEBP1 protein decreased significantly in broilers with PHS. These studies laid a foundation for further exploration of the mechanism of pulmonary artery remodeling. In addition, the PEBP1 polyclonal antibody provided convenience for further study of the role of PEBP1 in PHS.

Clinicopathologic features, comorbid diseases, and prevalence of pulmonary hypertension in dogs with bronchomalacia.

BACKGROUND: Reports of clinicopathologic features of bronchomalacia (BM) differ because of inconsistent definitions and frequent prevalence of comorbid cardiopulmonary disease. Pulmonary hypertension (PH) secondary to BM is poorly described. OBJECTIVES: Dogs with BM will be older but of any somatotype, and increased expiratory effort, ≥1 comorbid disease, and PH will be more common than in dogs without BM. ANIMALS: Client-owned dogs (n = 210) evaluated for respiratory signs. METHODS: Medical records of dogs with paired inspiratory: expiratory-breath-hold computed tomography, tracheobronchoscopy, or both between January 2016 and December 2019 were retrospectively reviewed. Comparisons between dogs with and without BM using Mann-Whitney rank sum or χ2 tests (P < .05 significant were made). Because of high numbers of variables, criteria with high prevalence (>25%) were identified (n = 10) for univariate analysis (P < .005 significant). Significant variables were submitted for multivariate analysis. RESULTS: Bronchomalacia was identified in 41% of dogs of all sizes/somatotypes; 38% were >10 kg. All dogs with BM had ≥1 comorbid cardiopulmonary disorder. Dogs with BM were significantly older (P < .001), smaller (P < .001), and were more likely diagnosed with tracheal or mainstem bronchial collapse (P < .001) or bronchiectasis (P < .001). Multivariate analysis confirmed associations with age, tracheal or mainstem bronchial collapse, and bronchiectasis. In dogs with BM, PH was more prevalent. CONCLUSIONS AND CLINICAL IMPORTANCE: Although significantly more common in older, smaller dogs, BM occurs in dogs of all sizes and in all instances with comorbidities. Echocardiography should be considered in dogs with BM to identify PH.

Impacts of caffeine on resistant chicken's performance and cardiovascular gene expression.

We previously reported a study on 288 broiler (Gallus gallus) chicks who received caffeine in water between days 3 and 42, at levels of 0, 6.25, 12.5, 25, 50 and 100 mg/kg body weight (BW)/day. In the previous report, we found that caffeine caused pulmonary hypertension (PH)-associated mortality in a significant minority (20%-30%) of birds, including right ventricular hypertrophy and ascites. We have also shown a significant upregulation of the serotonin transporter (SERT), troponin T2, adenosine A1 receptor (ADORA1) and phosphodiesterase 5A (PDE5) in chicken suffering from PH. Here, we examine the resistant (survived) chicks from the first study that had not died due to acute heart failure and did not have clinical signs of pulmonary hypertension. Our goal was to determine whether birds who lacked overt signs of disease had subclinical manifestations, including similar changes in gene expression, growth rates and altered systemic haemodynamics. We found that growth was significantly increased by caffeine consumption (p < 0.01) at low doses; however, dosage over 50 mg/BW/d had remarkable adverse effects on growth (p < 0.01). Blood pressure, troponin T2 and PDE5 gene expression were not significantly altered by caffeine administration (p > 0.05). However, SERT gene expression linearly increased with increasing caffeine dosage (p < 0.01). The impact of caffeine on ADORA1 gene expression was dose dependent and nonlinear. In conclusion, despite the significant effects of caffeine on birds' growth, no significant negative effects of caffeine were observed on the cardiovascular function of resistant chickens. This work provides valuable information for further study on different dosage of caffeine in an animal model.

Unmasking of left heart dilation following treatment for precapillary pulmonary hypertension.

A 13-year-old spayed female dog was referred for a history of tachypnea and dyspnea. Severe pulmonary hypertension was diagnosed based on tricuspid regurgitation velocities and 2-dimensional echocardiography. Left atrial size was normal at the time of this diagnosis. However, following treatment with a selective phosphodiesterase inhibitor, echocardiography revealed unmasking of left heart dilation. Key clinical message: If phosphodiesterase inhibition therapy is deemed appropriate in patients with hemodynamically important myxomatous mitral valvular disease, using the lowest effective dosage and careful monitoring with echocardiography ± thoracic radiographs should be considered.

Découverte de dilatation cardiaque gauche après traitement d'hypertension pulmonaire précapillaire. Une chienne stérilisée de 13 ans a été référée pour une histoire de tachypnée et de dyspnée. Une hypertension pulmonaire sévère a été diagnostiquée sur la base des vitesses de régurgitation tricuspidienne et de l'échocardiographie bidimensionnelle. La taille de l'oreillette gauche était normale au moment de ce diagnostic. Cependant, après un traitement avec un inhibiteur sélectif de la phosphodiestérase, l'échocardiographie a révélé une dilatation du coeur gauche.Message clinique clé :Si un traitement par inhibition de la phosphodiestérase est jugé approprié chez les patients présentant une pathologie valvulaire mitrale myxomateuse évidente et hémodynamiquement significative, l'utilisation de la dose efficace la plus faible et une surveillance attentive par échocardiographie avec ou sans radiographies thoraciques doivent être envisagées.(Traduit par Dr Serge Messier).

The prevalence of pulmonary hypertension assessed using the pulmonary vein-to-right pulmonary artery ratio and its association with survival in West Highland white terriers with canine idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) is a known co-morbidity in West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) has recently been described for the detection of pre-capillary PH in dogs. The objective of the present study was to estimate the prevalence of PH at diagnostic, in WHWTs affected with CIPF, by using PV/PA, in comparison with a group of healthy breed-matched controls (CTRLs). Additional study objective was to explore whether the presence of PH at initial diagnosis of CIPF impacted survival time in dogs treated with sildenafil. RESULTS: Twenty-five client-owned WHWTs presented with CIPF and 19 CTRLs were included in the study. PV/PA in either two-dimensional mode (2D) or time-motion mode or both were measured from cineloops in each dog. Dogs were classified according to PV/PA value into non/mild PH (PV/PA measured in 2D ≥ 0.7) or moderate/severe PH (PV/PA < 0.7). Survival data of WHWTs affected with CIPF were extracted from medical record to assess association between presence of PH at diagnosis and outcome. 60 % overall prevalence for moderate/severe PH was estimated in this cohort of WHWTs presented with CIPF vs. 5 % in CTRLS (P = 0.0002). The presence of moderate/severe PH at initial presentation was not associated with survival. CONCLUSIONS: Results of the present study confirm a high prevalence of PH at diagnosis in WHWTs affected with CIPF and highlight the utility of PV/PA as a non-invasive surrogate for assessment of PH in this population.

Accuracy of echocardiographically estimated pulmonary artery pressure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Echocardiographically identified pulmonary hypertension is an independent predictor of poor outcome in dogs affected by myxomatous valvular degeneration (MMVD). Systolic pulmonary arterial pressure is routinely estimated based on its relationship with the Doppler-determined velocity of tricuspid regurgitation as defined by the simplified Bernoulli equation (sPAP_D). Experimental studies suggest that the method is imperfect, but its accuracy in dogs with MMVD is not known. ANIMALS: Twenty dogs affected by MMVD that had cardiac remodeling and measurable tricuspid regurgitation. METHODS: A flow-directed thermodilution monitoring catheter was percutaneously placed in the right external jugular vein and advanced to the main pulmonary artery. Pulmonary arterial systolic pressure was recorded (systolic pulmonary arterial pressure obtained by right heart catheterization [sPAP_C]). A second operator contemporaneously acquired tricuspid regurgitant velocity spectra to calculate sPAP_D. Each operator was blinded to the result of the other techniques. RESULTS: Technical difficulties prevented the analysis of catheterization data in two dogs. Eighteen measurement pairs were therefore used for comparison of sPAP_C and sPAP_D through correlation and Bland-Altman analysis. A statistically significant bias between sPAP_C and sPAP_D (mean difference = 0.5 mmHg; confidence interval = -6.5 mmHg, +7.5 mmHg) was not detected. The interval of agreement between the techniques was wide (-27.3 mmHg, +28.2 mmHg). A significant linear association between the two techniques was not identified (r = 0.11, p=0.17). CONCLUSION: Echocardiographically estimated pulmonary artery pressure poorly agrees with sPAP_C measurement in dogs affected by MMVD and cardiac remodeling with or without previously diagnosed congestive heart failure. In these dogs, sPAP_D could under- or over-estimate sPAP_C by more than 20 mmHg, and therefore caution should be used when interpreting sPAP_D.

Utility of tricuspid annular plane systolic excursion normalized by right ventricular size indices in dogs with postcapillary pulmonary hypertension.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is a common right ventricular (RV) function indicator. However, TAPSE was not decreased in dogs with myxomatous mitral valve disease (MMVD) and postcapillary pulmonary hypertension (PH) because of its load, angle, and body weight dependency, and TAPSE was considered a preload-dependent index. OBJECTIVES: To evaluate the utility of TAPSE normalized by RV size in dogs with postcapillary PH. ANIMALS: Twenty healthy dogs and 71 MMVD dogs with or without PH. METHODS: In this prospective observational study, end-diastolic RV internal dimension (RVIDd), end-diastolic and end-systolic RV area, and end-diastolic RV wall thickness were measured as RV size indices. The TAPSE was measured using B-mode and M-mode methods. Normalized TAPSE was calculated by dividing TAPSE by each RV size index. The RV strain was obtained as the detailed RV function using 2-dimensional speckle tracking echocardiography. All indices were compared among the PH severity groups and in the presence of right-sided congestive heart failure (R-CHF). RESULTS: Although nonnormalized TAPSE was higher with PH severity progression, each normalized TAPSE showed a significant decrease in the severe PH group (P < .05). The TAPSEB-mode /RVIDd ratio had high area under the curve to predict R-CHF and had moderate correlation with RV strain (P < .05). The TAPSEB-mode /RVIDd and left atrial-to-aortic diameter ratios were independent predictors for R-CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Normalized TAPSE could reflect RV systolic dysfunction in dogs with severe PH, which could not be detected by nonnormalized TAPSE. The TAPSEB-mode /RVIDd ratio might predict R-CHF with high sensitivity and reproducibility.

Noninvasive assessment of fluid responsiveness for emergency abdominal surgery in dogs with pulmonary hypertension: Insights into high-risk companion animal anesthesia.

OBJECTIVE: Optimizing cardiac stroke volume during high-risk surgical anesthesia is of particular interest with regard to a therapeutic target to reduce the incidence of postoperative complications. However, intensive fluid management in critically ill small animals with pulmonary hypertension (PH) has been empirically performed, and thus it can be challenging. Stroke volume variation (SVV) has been used as a dynamic preload predictor of fluid responsiveness. We hypothesized that if SVV exhibited robust reliability in the setting of hemodynamically unstable condition, it would provide more precise information on fluid resuscitation to translate it into veterinary anesthesia. Thus the aim of this study was to investigate the utility of SVV measured by the electrical velocimetry (EV) method for predicting fluid responsiveness in dogs with PH. METHODS: Sixteen dogs undergoing emergency abdominal surgery and diagnosed with PH secondary to myxomatous mitral valve disease (MMVD) on preoperative transthoracic echocardiogram were included. Dogs were randomly assigned to 2 groups with and without inotropic cardiac support with dobutamine. Hemodynamic measurements including stroke volume and SVV derived from the EV device were performed under general anesthesia before (baseline) and after surgery (fluid challenge with a colloid solution defined by a SV increase of ≥ 10%). RESULTS: In both groups, SVV elevated significantly after abdominal surgery compared with baseline. In dobutamine infused group, the SVV values decreased significantly after fluid challenge (P < 0.05) with a greater number of responders than saline infused control group (P < 0.01). Receiver operating curve analysis of SVV confirmed high positive predictive value for dogs during dobutamine infusion (P < 0.05; cut-off value of 15%; specificity 90%, sensitivity 82%). CONCLUSIONS: Noninvasive EV monitoring may be useful for the prediction of fluid responsiveness in critically ill dogs with left-sided heart failure-related PH. This normalization of dynamic preload indices, which could be achieved more precisely under inotropic support, may prevent further detrimental consequence of fluid loading.