BackgroundPulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated. Hypothesis/objectivesThe presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH. AnimalsTwo hundred and twelve client-owned dogs. MethodsCase review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long-term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3m/s. ResultsTwo hundred and twelve were identified. Eighty-three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P1.7 (P=.0002), normalized left-ventricular end-diastolic diameter (LVEDn) >1.73 (P=.048), and tricuspid regurgitation pressure gradient (TRPG) >55mmHg (P=.009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55mmHg (HR 1.8 95% CI 1-2.9; P=.05) and LA/Ao>1.7 (HR 2 95% CI 1.2-3.4; P=.01) remained significant predictors of worse outcome in the multivariate analysis. Conclusions and Clinical ImportanceIn dogs with MMVD, moderate to severe PH worsens outcome.
Background: Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Methods: Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. Results: A higher frequency of virus positive cases was found in IPF patients than in controls (p=0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p=0.01), poorer performance in the six minute walking test (6MWT; p=0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p=0.002 and p=0.004) and higher TGF-beta expression (p=0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p=0.03), poorer performance in the 6MWT (p=0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Conclusion: Herpesviral infections may contribute to the development of PH in IPF patients.
Canine pulmonary hypertension is a clinical condition that needs to be adequately investigated and recognised because of the lack of specific clinical signs, the potential for rapid and irreversible deterioration of pulmonary vascular function and the development of right-sided heart failure. In recent years, many studies have been published on pulmonary hypertension, improving the understanding of its pathophysiology, the accuracy of diagnostic tests and the management of affected patients. This article provides updated information on pulmonary hypertension and serves as a resource for veterinarians regarding the interpretation of diagnostic tests and the clinical management of affected dogs.
BackgroundHypothesis/ObjectivesRight ventricular (RV) enlargement and dysfunction are associated with prognosis in humans with pulmonary hypertension (PH). To assess RV size and systolic function in dogs with PH and to determine if they are associated with disease severity and right-sided congestive heart failure (R-CHF). AnimalsMethods89 dogs with PH and 74 healthy dogs. Prospective observational study. PH was classified according to the tricuspid regurgitation pressure gradient. RV end-diastolic area (RVEDA) index was calculated as RVEDA divided by body surface area. RV systolic function was assessed with the tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (FAC) normalized for body weight (TAPSEn and FACn, respectively). ResultsConclusions and Clinical ImportanceRVEDA index was higher in dogs with moderate PH (10.8 cm(2)/m(2); range, 6.2-14.4 cm(2)/m(2)) and severe PH (12.4 cm(2)/m(2); range, 7.7-21.4 cm(2)/m(2)) than in those with mild PH (8.4 cm(2)/m(2); range, 4.8-11.6 cm(2)/m(2)) and control dogs (8.5 cm(2)/m(2); range, 2.8-11.6 cm(2)/m(2); P < .001). RVEDA index was significantly higher in dogs with R-CHF (13.7 cm(2)/m(2); range, 11.0-21.4 cm(2)/m(2)) than in dogs without R-CHF (9.4 cm(2)/m(2); range, 4.8-17.1 cm(2)/m(2); P < .001). The severity of tricuspid regurgitation (TR) was the only independent predictor of the RVEDA index (P < .001). TAPSEn and FACn were not significantly different among varying degrees of PH severity and between dogs with and without R-CHF. The RVEDA index can be used to evaluate RV size in dogs. It can provide additional information in dogs with PH and predict R-CHF. Severity of TR is the main determinant of RV enlargement in dogs with PH.
Right atrial area (RAA) is a prognostic factor in human patients with pulmonary arterial hypertension (PAH). Reference intervals for RAA have been described in healthy dogs. To evaluate RAA indexed to the body surface area in dogs with PAH as an indicator of right atrial size, PAH severity and right-sided congestive heart failure (R-CHF). A total of 119 client-owned dogs, 48 dogs with PAH and 71 control dogs. Prospective observational study. Pulmonary arterial hypertension was classified according to the tricuspid regurgitation pressure gradient (TRPG) as mild (36-50 mmHg), moderate (51-75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the RAA divided by body surface area. The RAA index was higher in dogs with moderate PAH (13.3 cm /m ; range, 3.4-24.7 cm /m ) and severe PAH (12.1 cm /m ; range, 5.4-21.8 cm /m ) than in those with mild PAH (6.7 cm /m ; range, 4.8-10.7 cm /m ) or in controls (7.3 cm /m ; range, 4.2-10.2 cm /m ; P 12.3 cm /m (sensitivity, 100%; specificity, 89.5%). In dogs with PAH, severity of tricuspid regurgitation (TR) was the only independent predictor of RAA index based on multivariate analysis (P < 0.02). The RAA index can be used to evaluate right atrial size in dogs and may be more effective than TRPG in predicting R-CHF in dogs with PAH. The severity of TR is the main determinant of the RAA index in dogs with PAH.
A 4-year-old, 5.9-kg female Japanese Spitz presented with syncope and exercise intolerance. Echocardiography revealed an ostium primum atrial septal defect (ASD), a cleft mitral valve, mitral valve regurgitation (MR), and tricuspid regurgitation (TR) (velocity: 3.6 m/sec, pressure gradient: 52 mmHg), leading to a diagnosis of partial atrioventricular septal defect (AVSD) with moderate pulmonary hypertension (PH). Open-heart surgery using cardiopulmonary bypass was performed through right atriotomy. The cleft of the mitral valve was sutured with polypropylene and the AVSD was closed using an autologous pericardial patch fixed with glutaraldehyde. No postoperative pulmonary hypertensive crisis occurred. Shunting flow through the ASD, TR and PH had completely disappeared 2 months postoperatively; however, moderate MR persisted. The dog is still alive 5 years postoperatively without clinical signs.
Pulmonary hypertension (PH) is a major disease in the broiler breeding industry. During PH, the pulmonary artery undergoes remodelling, which is caused by pulmonary vascular smooth muscle cell proliferation. CyclinD1 regulates cell proliferation. This study investigated the role of cyclinD1 in the development of PH in broilers, and which bioactivators and signalling pathway are involved in the pathological process. The PH group contained 3-4-week-old broilers with clinical PH, and the healthy group broilers from the same flock without PH. Histopathology indicated pulmonary arterial walls were thicker in the PH group compared with the healthy group. Target gene expressions of macrophage migration inhibitory factor (MIF), extracellular signal-regulated kinase (ERK), and cyclinD1 detected by quantitative real-time PCR were upregulated in the PH group compared with the healthy group. Immunohistochemistry showed MIF, phosphorylated ERK (p-ERK) and cyclinD1 were present on pulmonary vascular walls; MIF was present in the cytoplasm of arterial endothelial cells and smooth muscle cells; p-ERK and cyclinD1 were present in smooth muscle cell cytoplasm. Western blotting demonstrated that MIF, p-ERKand cyclinD1 levels were significantly higher (P < 0.01) in the PH group compared with the healthy group. In summary, increased MIF in PH broiler pulmonary arteries upregulated cyclinD1 via the ERK signalling pathway to induce pulmonary vascular smooth muscle cell proliferation, causing pulmonary artery remodelling and hypertension.
Background Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension (PAH) in humans and can be classified in idiopathic, heritable, drug and radiation-induced, and associated with connective tissue disease or human immunodeficiency virus infection. Recently, biallelic mutations of the EIF2AK4 gene have been discovered as a cause for an autosomal recessive form of PVOD in humans. In dogs, PAH is poorly characterized and is generally considered to be idiopathic or secondary to (for example)congenital left-to right cardiovascular shunts or heartworm disease. However, recently, the pathologic features resembling human PVOD were retrospectively described in post-mortem lung samples of dogs presenting with respiratory distress and idiopathic pulmonary hypertension (PH), which suggests that PVOD contributes to an unknown percentage of cases with unexplained PH. In dogs, information on the clinical presentation of PVOD is scarce and the cause and pathogenesis of this disease is still unknown. Case presentationAn 11-year-old, intact male German Shepherd dog (GSD) was presented with a 2-day history of acute-onset dyspnea and generalized weakness. Physical examination, laboratory analysis, thoracic radiography, echocardiography, a computed tomography scan and an ante mortem lung biopsy demonstrated severe arterial hypoxemia and severe PH but were not diagnostic for a known disease syndrome. Based on the poor reaction to therapy with oxygen, sildenafil, pimobendan and dexamethasone the dog was euthanized. Histopathology of the lungs showed venous and arterial remodelling, segmental congestion of alveolar capillaries and foci of vascular changes similar to human pulmonary capillary hemangiomatosis, indicating that the dog suffered from PVOD. Whole genome sequencing analysis was performed on the case and a healthy GSD. Validation was performed by Sanger sequencing of five additional GSD's unknown for any form of respiratory stress and aged >= 10 years. No causal variants were found in the genes that are known to be involved in human PVOD and PAH. ConclusionsThis case report confirms that PVOD should be a diagnostic consideration in dogs presenting with dyspnea and unexplained PH. In the present case, no casual genetic mutations known to be involved in humans with PVOD and PAH were found.
A four month-old kitten was referred at the Veterinary Teaching Hospital of Teramo, Italy. Physical examination, echocardiography, thoracic radiography, copromicroscopy and biomolecular assays led to a diagnosis of severe parasitic bronchopneumonia by complicated by pulmonary hypertension. A single administration of a spot on solution containing imidacloprid 10%/moxidectin 1% was effective in stopping larval shedding but clinical, radiographic and echocardiographic signs of bronchopneumonia and pulmonary hypertension still persisted after further follow-ups. While cases of pulmonary hypertension are known in infections by , this is the first report of irreversible pulmonary hypertension in a kitten with troglostrongylosis.