Retrospective evaluation of sildenafil citrate as a therapy for pulmonary hypertension in dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.     

Diagnosis and treatment of congestive heart failure secondary to dilated cardiomyopathy in a hedgehog

A one‐year‐old African pygmy hedgehog (Atelerix albiventris) was evaluated for severe respiratory distress. Physical examination findings included marked dyspnoea, cyanosis and tachypnoea. Radiographic findings included an enlarged heart and pulmonary oedema, and dilated cardiomyopathy was confirmed via echocardiogram. The patient was treated for congestive heart failure because of dilated cardiomyopathy with furosemide, enalapril, pimobendan and l‐carnitine. Within 24 hours of treatment, the pulmonary oedema and cyanosis had resolved. Following discharge, clinical improvement was noted by the owner and echocardiogram confirmed improved fractional shortening. Cardiomyopathy has been reported at post‐mortem examination in hedgehogs, but there are no reports of ante‐mortem diagnosis and treatment. Performing baseline cardiac assessment in hedgehogs is recommended, and treatment with l‐carnitine and pimobendan may improve outcome, as carnitine deficiency is a possible cause of cardiomyopathy in hedgehogs. Successful emergency treatment of congestive heart failure in the hedgehog of this report may be effective for other hedgehogs presented with similar clinical signs .     

A case of long-term sildenafil therapy in a young dog with pulmonary hypertension

A 7-month-old male Papillon was presented to us with mild dyspnea, cyanosis and a diastolic murmur detected by cardiac auscultation. Echocardiography revealed severe pulmonary arterial hypertension (PH), and administration of 1 mg/kg of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, twice daily was initiated. Exercise capacity, cyanosis, dyspnea and cardiac murmur were improved after therapy for 4 weeks. PCV was remarkably high (74%) after therapy for 3 years, however, increasing the dose of sildenafil decreased this value (60%). Follow-up after therapy for 4 years revealed that treatment with oral sildenafil only continued to provide the dog with an excellent quality of life, without any side effects.     

Multimodality imaging of an azygous continuation of the caudal vena cava in a dog with pulmonary thromboembolic disease

A 5‐year‐old spayed female English Bulldog was evaluated for acute anorexia, lethargy, respiratory distress, and syncope. Contrast‐enhanced computed tomography revealed the vascular malformation of azygous continuation of the caudal vena cava with extensive thrombus formation and pulmonary arterial thromboembolic disease. The patient was hospitalized for supportive treatment and was prescribed long‐term clopidogrel therapy. The patient survived to discharge and at last follow‐up remained clinically stable. While this vascular malformation has been reported in canines, to the authors’ knowledge, this is the first reported case of pulmonary thromboembolic disease in a canine concurrent with this condition.     

Pulmonary manifestations of heartworm disease

The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.     

Pathophysiologic studies of calves given 3-methylindole intraruminally

Intraruminal administration of 0.25 g of 3-methylindole (3MI; skatole/kg of body weight) to seven young calves generally caused mild respiratory signs and lesions, accompanied by only slight changes in cardiopulmonary function. Moderate depression, trembling, and irregular respiratory rate were observed between postadministration hours (PAH) 6 and 12. By PAH 24 at this dosage, abnormal clinical signs were not present. Statistically significant (P less than or equal to 0.05) changes observed in blood gas data from the seven calves were a decrease in aortic oxygen tension at PAH 12, increases in free-flowing venous oxygen tension in the intervals between PAH 6 and 12 and between PAH 6 and 24, and an increase in occluded venous oxygen tension at PAH 24. All calves had increases (although generally not statistically significant) in heart rate, cardiac output, cardiac index, stroke volume, and stroke index after 3MI administration. Mean aortic and pulmonary arterial pressure changes were generally small and variable. At necropsy, the lungs of the calves did not collapse when the thorax was opened. Patchy areas of consolidation (0.5 cm in diameter) were scattered throughout the parenchyma. Pulmonary edema or emphysema was not observed grossly. Microscopically, the alveolar septae were irregularly thickened because of edema, infiltration by polymorphonuclear and mononuclear cells, and vascular congestion. Interstitial lesions were patchy in distribution and severity and corresponded to the areas of consolidation observed grossly. Alveolar epithelial hypertrophy and hyperplasia were present, and an occasional focus of alevoli contained fluid of edema. Degeneration of individual hepatocytes was observed in scattered areas of the liver, especially in the periportal areas. It was concluded that differences in 3MI dosage response may exist between young calves and adult cattle in which calves are more resistant to the pulmonary cytotoxicity of 3MI.     

Cardiac effects of pulmonary disease.

Pulmonary hypertension (PHT) is the primary cardiac consequence of pulmonary disease. It develops as alveolar hypoxia of pulmonary disease, coupled with vasoactive and mitogenic substances released from pulmonary endothelial and vascular smooth muscle cells damaged by the primary disease process, mediates arterial vasoconstriction and vascular remodeling to raise pulmonary vascular resistance. Independent of the underlying pulmonary disease, PHT produces clinical signs of respiratory distress, exercise intolerance, syncope, and right heart failure. Diagnosis of PHT is made by estimation of pulmonary artery pressures by means of continuous-wave Doppler echocardiographic assessment of tricuspid or pulmonic regurgitant flow velocity. Treatment of PHT is directed at the underlying pulmonary disease but may also aim to attenuate pulmonary artery pressure and limit the clinical sequelae of PHT. No treatments are of proven benefit in veterinary patients; irrespective of the nature of the inciting pulmonary disease, the prognosis is often grave.     

Endotoxic shock in the awake young pig: absence of beneficial effect of prednisolone sodium succinate treatment

In nonanesthetized young pigs, the influence of prednisolone sodium succinate therapy on a 65% lethal dose of Escherichia coli endotoxin was studied by evaluating clinical signs, several hemodynamic variables, survival rate, and changes seen at necropsy. Endotoxin infusion induced reproducible clinical signs characterized by nausea, vomiting, dyspnea, cyanosis, and moderate excitement followed by severe CNS depression. Among the hemodynamic variables, there were decreases in arterial blood pressure and cardiac output and increases in pulmonary arterial pressure, heart rate, and total peripheral and pulmonary vascular resistances. Core temperature and arterial pH did not change significantly. Survival rate at 30 hours after the start of the endotoxin infusion was 35%. According to the necropsy, marked edema and hemorrhages were in several organs. Treating the experimental animals with prednisolone sodium succinate (3 injections of 10 mg/kg of body weight after the start of the endotoxin infusion) did not influence any of the monitored hemodynamic variables, except for arterial blood pressure, which was higher at the end of the hemodynamic recording period (270 minutes after the start of the endotoxin infusion). Clinical signs, survival rate, and changes at necropsy were similar in both treated and nontreated pigs. This lack of effect can be due to an inappropriate dosage of the steroid or failure of steroid treatment to alleviate endotoxin-mediated effects.     

Laryngoscopy

The larynx normally functions in vocalization, deglutition, and respiration. There is no substitute for direct laryngoscopy in animals suspected of having laryngeal disease. Clinical signs that should alert the veterinarian include cough, choking while eating or drinking, exertional cyanosis and syncope, noisy breathing, inspiratory dyspnea, stridor, and significant change in sound production. Controlled anesthesia is mandatory for animals with suspected laryngeal disease because many of these patients have compromised respiratory function. Laryngoscopy is used to note abnormalities in the shape, color, and motility of the larynx with special attention to correlating the movement of the arytenoid cartilages and vocal folds with the respiratory cycle.     

Arterial thromboembolism: risks, realities and a rational first-line approach

PRACTICAL RELEVANCE: Feline arterial thromboembolism (ATE) is a common but devastating complication of myocardial disease, often necessitating euthanasia. A combination of endothelial dysfunction and blood stasis in the left atrium leads to local platelet activation and thrombus formation. Embolisation of the thrombus results in severe ischaemia of the affected vascular bed. With the classic 'saddle thrombus' presentation of thrombus in the terminal aorta, the diagnosis can usually be made by physical examination. The prognosis is poor for cats with multiple limbs affected by severe ischaemia, but much better where only one limb is affected or motor function is present. PATIENT GROUP: Cats with left atrial enlargement secondary to cardiomyopathy are typically predisposed, although cats with hyperthyroidism, pulmonary neoplasia and supravalvular mitral stenosis may also be at risk. MANAGEMENT: Analgesia is the main priority, and severe pain should be managed with methadone or a fentanyl constant rate infusion. Congestive heart failure (CHF) requires treatment with furosemide, but tachypnoea due to pain can mimic signs of CHF. Thrombolytic therapy is not recommended, but antithrombotic treatment should be started as soon as possible. Aspirin and clopidogrel are well tolerated. EVIDENCE BASE: Several observational studies of ATE have been reported. No randomised, blinded, controlled studies have been reported in cats at risk, for either treatment or prevention of ATE, although such a study comparing aspirin and clopidogrel in cats is currently under way.     

Diagnosis of pulmonary hypertension

Pulmonary hypertension may complicate a variety of congenital or acquired cardiac and pulmonary conditions. This vascular disorder results from conditions that lead to a chronic increase in left atrial pressure, increased pulmonary blood flow, or increased pulmonary vascular resistance. Definitive diagnosis requires cardiac catheterization and detection of systolic and mean pulmonary artery pressures exceeding 30 and 20 mm Hg, respectively. Clinical signs and historical complaints reflect underlying cardiac or pulmonary conditions, although syncope may be a predominant finding. Radiographic changes are nonspecific; however, right ventricular enlargement and enlarged pulmonary arteries should increase suspicion for the disorder. Estimates of pulmonary arterial pressure may be obtained through Doppler echocardiography. This requires detection of a high-velocity regurgitant jet across the tricuspid or pulmonic valve. Further investigation is required to determine how pulmonary hypertension impacts therapy and prognosis for dogs and cats with cardiac and pulmonary diseases.     

Diagnosis of pulmonary thromboembolism in a cat using echocardiography and pulmonary scintigraphy

A 10-year-old male cat was presented with sudden onset of respiratory difficulties. Clinical examinatlon revealed an acute dyspnoea with cyanosis associated with a left systolic heart murmur. Standard thoracic radiographs excluded pulmonary oedema and showed very few pulmonary changes given the intensity of the respiratory compromlse. Echocardiographic examination revealed hypertrophic cardiomyopathy and a thrombus In the right pulmonary artery. Pulmonary sclntlgraphy confirmed a pulmonary thromboembolism with hypovascularisatlon of the left cranial lobe and of the ventral segment of the right lobe. Conservative treatment was instituted using an antibiotic (doxycycllne), anticoagulants (heparin, coumadine) and a calcium lnhlbitor (diltiazem). The cat was given absolute rest. The general condition of the animal improved.     

Adjunct ambrisentan therapy had clinical benefits in 5 dogs with sildenafil-refractory pulmonary hypertension

Although sildenafil is used in dogs with severe pulmonary hypertension, they sometimes become resistant and clinical signs deteriorate over time. The objective of this study was to determine the benefits of adjunct ambrisentan therapy in dogs with sildenafil-refractory pulmonary hypertension. In 5 dogs with severe pulmonary hypertension with deteriorating clinical signs despite ongoing sildenafil treatment, adding ambrisentan improved appetite, activity, and respiratory functions. Although peak tricuspid valve regurgitation velocity, as measured by Doppler echocardiography, did not necessarily decrease after ambrisentan administration, there was improved partial pressure of arterial oxygen and the alveolar-arterial oxygen gradient, with no apparent side effects. We concluded that ambrisentan has potential as an adjunct treatment in dogs with pulmonary hypertension that are refractory to sildenafil therapy.Key clinical message:Ambrisentan improved clinical signs in dogs with sildenafil-refractory pulmonary hypertension.     

Tetralogy of Fallot and atrial septal defect in a white Bengal Tiger cub (Panthera tigris tigris)

A 3-week-old female white Bengal Tiger cub (Panthera tigris tigris) presented with acute onset tachypnoea, cyanosis and hypothermia. The cub was severely hypoxaemic with a mixed acid–base disturbance. Echocardiography revealed severe pulmonic stenosis, right ventricular hypertrophy, high membranous ventricular septal defect and an overriding aorta. Additionally, an atrial septal defect was found on necropsy, resulting in the final diagnosis of Tetralogy of Fallot with an atrial septal defect (a subclass of Pentalogy of Fallot). This report is the first to encompass arterial blood gas analysis, thoracic radiographs, echocardiography and necropsy findings in a white Bengal Tiger cub diagnosed with Tetralogy of Fallot with an atrial septal defect.     

Chronic pulmonary disease in West Highland white terriers.

This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to years. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased Interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.     

Clinical Efficacy of Sildenafil in Treatment of Pulmonary Arterial Hypertension in Dogs

Background: Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. Hypothesis/Objectives: Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. Animals: Thirteen dogs with echocardiographic evidence of PAH. Methods: Prospective short‐term, randomized, placebo controlled, double‐blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. Results: Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34–83 mmHg) than at baseline (median, 72 mmHg; range, 61–86 mmHg; P= .018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49–197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101 ± 47 versus 74 ± 32; P= .05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. Conclusions and Clinical Importance: Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.     

Lung Injury Leading to Respiratory Distress Syndrome in Young Dalmatian Dogs

A progressive pulmonary disease resulting in severe respiratory failure and death in an average of 3 weeks was diagnosed in 11 young Dalmatian dogs. The dogs were from 4 litters, all genetically related by a common ancestor. The initial clinical signs were tachypnea and noisy respiration. Respiratory distress developed shortly before death and was characterized by strenuous and rapid respirations, along with cyanosis and vomiting. On blood gas analysis, there were severe arterial hypoxemia, hypercapma, and marked alveolar-arterial oxygen difference. Radiographically, a diffuse pattern of alveolar, interstitial, and peribronchial densities was observed in the lungs. Most dogs developed pneumomediastinum and gastroesophageal intussusception in the terminal phase of the disease. There was no response to treatment with antibiotics, corticosteroids, diuretics, or oxygen. At necropsy, the lungs were wet, heavy, and relatively airless. Absence of 1 kidney in 2 dogs and severe internal hydrocephalus in 2 dogs were additional necropsy findings. Pulmonary histopathology included metaplasia and atypia of the alveolar and bronchiolar epithelium, a nonpurulent inflammatory reaction characterized mainly by mononuclear cells and macrophages, eosinophilic hyaline membrane formation, and focal pulmonary fibrosis. The histological manifestations were typical of acute lung injury. Clinically, the findings were consistent with adult respiratory distress syndrome (ARDS), except for the relatively long course. No known risk factors for ARDS, such as trauma, toxin exposure, infection, or endotoxemia could be identified. The relationship of the other abnormalities (ie, renal aplasia, hydrocephalus) to the pulmonary disease also remains obscure. An inherited defect is suspected, because segregation analysis of the 4 litters suggests autosomal recessive inheritance.     

Acute lung injury/acute respiratory distress syndrome in 15 foals

REASONS FOR PERFORMING STUDY: Few reports exist in the veterinary medical literature describing clinical and pathological findings resembling conditions described as (ALI) and acute respiratory distress syndrome (ARDS) in man. OBJECTIVES: To document history, clinical, laboratory and diagnostic findings, treatment and outcome of foals age 1-12 months diagnosed with ALI/ARDS at a referral hospital. METHODS: Medical records, including radiographic, cytological, microbiological, serological and post mortem findings, were reviewed in a retrospective manner to identify foals with acute onset of respiratory distress, a partial pressure of arterial oxygen (PaO2) to fraction of oxygen in inspired gases (FiO2) ratio of < or = 300 mmHg, pulmonary infiltrates on thoracic radiographs or post mortem findings consistent with ALI/ARDS. RESULTS: Fifteen foals age 1.5-8 months were included in the study. Seven foals had previously been treated for respiratory disease, and all foals developed acute respiratory distress <48 h prior to presentation. Findings on presentation included tachycardia and tachypnoea in all foals, with fever recorded in 8 cases. Eight cases met the criteria for ALI and 7 for ARDS. Radiographic findings demonstrated diffuse bronchointerstitial pattern with focal to coalescing alveolar radiopacities. An aetiological agent was identified in foals ante mortem (n = 6) and post mortem (n = 4). All foals were treated with intranasal oxygen and antimicrobial drugs; 13 received corticosteroids. Nine patients survived, 4 died due to respiratory failure and 2 were subjected to euthanasia in a moribund state. Follow-up was available for 7 foals; all performed as well as age mates or siblings, and one was racing successfully. CONCLUSIONS: A condition closely meeting the human criteria for ALI/ARDS exists in foals age 1-12 months and may be identical to previously described acute bronchointerstitial pneumonia in young horses. POTENTIAL RELEVANCE: ALI/ARDS should be suspected in foals with acute severe respiratory distress and hypoxaemia that is minimally responsive to intranasal oxygen therapy. Treatment with systemic corticosteroids, intranasal oxygen and antimicrobials may be beneficial in foals with clinical signs compatible with ALI/ARDS.     

Successful treatment of cryptococcal pneumonia in a pony mare

A 20-year-old Welsh Mountain Pony (212 kg) mare was initially presented for a chronic cough, fever, weight loss and low grade abdominal pain. She later developed dyspnoea, tachypnoea and exercise intolerance. The presence of multiple masses (up to 17 cm diameter) in the pulmonary parenchyma was established using lateral thoracic radiography and transthoracic ultrasonography. Encapsulated, budding yeasts were observed in smears made from transtracheal washings and needle aspirates of the pulmonary lesions. Cryptococcus gattii (synonym: Cryptococcus neoformans variety gattii; Cryptococcus bacillisporus) was cultured from the transtracheal washings and aspirates of the lung masses. The pony was successfully treated using daily intravenous infusions of amphotericin B (typically 0.5 mg/kg in 1 L 5% dextrose in water over 1 h, following premedication with 50 mg flunixin intravenously) over a 1 month period, until a cumulative dose of 3 g had been administered. Treatment was considered to be successful on the basis of progressive improvement in clinical signs, reduction in the size of pulmonary cryptococcomas, 48 kg weight gain and a reduction in the cryptococcal antigen titre from 4096 to 256, 1 year after cessation of treatment.