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.     

Sildenafil citrate therapy in 22 dogs with pulmonary hypertension

BACKGROUND: Pulmonary hypertension (PH) is a disease condition characterized by abnormally increased pulmonary artery pressures and often is associated with a poor prognosis. Sildenafil is a phosphodiesterase inhibitor that causes pulmonary arterial vasodilation and reduction in pulmonary artery pressures. HYPOTHESIS: Treatment with sildenafil will improve echocardiographic determinants of PH in dogs, while also improving quality of life and survival. ANIMALS: Twenty-two dogs with clinical and echocardiographic evidence of pulmonary hypertension. METHODS: A retrospective study evaluating the effects of sildenafil on physical examination, ECG and radiographic findings, blood pressure and echocardiographic findings of PH, clinical score, and outcome was completed. PH was defined as a peak tricuspid regurgitation flow velocity > or = 2.8 m/s or a peak pulmonic insufficiency flow velocity > or = 2.2 m/s. RESULTS: Sixteen of 22 dogs with PH were elderly females of small body size. Their clinical score was significantly improved (P = .0003) with sildenafil treatment, but physical examination findings remained unchanged. Heart rate, respiratory rate, vertebral heart size, ECG heart rate, and systolic blood pressure did not change significantly with sildenafil treatment (P > .05). Peak tricuspid regurgitation flow velocities did not change significantly with the treatment of sildenafil, but selected systolic time intervals were significantly improved. Survival times for all dogs ranged from 8 to > 734 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Sildenafil did not significantly lower the degree of measurable PH in dogs. Clinical improvement and increased quality of life was seen with sildenafil treatment, despite lack of significant change in other variables.     

Effects of sildenafil citrate on five dogs with Eisenmenger's syndrome

Objectives : To determine the effect of sildenafil for dogs with Eisenmeger's syndrome and secondary erythrocytosis. Methods : This is a prospective, single arm, open‐label study. Five clinical dogs with Eisenmeger's syndrome and secondary erythrocytosis were included. New York Heart Association functional class, packed cell volume, pulmonary artery acceleration time to ejection time ratio and serum erythropoietin concentration were evaluated before and after sildenafil therapy (0·5 mg/kg, twice a day). Results : New York Heart Association functional class was significantly improved after one (median 2; range 1 to 2, P=0·031) and three months (median 2; range 1 to 2, P=0·031) of sildenafil therapy, compared with the baseline (median 3, range 2 to 3). Packed cell volume was significantly decreased after three months (median 59%; range 56 to 63, P=0·031) of therapy, compared with the baseline (median 71%; range 58 to 74). Acceleration time to ejection time ratio had increased and serum erythropoietin concentration had decreased particularly after 1 month of therapy, but there was no statistical significance. Clinical Significance : Sildenafil improved the clinical signs and secondary erythrocytosis in dogs with Eisenmeger's syndrome. Sildenafil therapy could be a useful treatment for dogs with Eisenmeger's syndrome.     

Pneumonitis associated with occult heartworm disease in dogs

Nine of 69 dogs with occult heartworm disease (13%) had allergic pneumonitis characterized by consistent clinical and radiographic signs. Although the clinical signs were severe, the degree of radiographic pulmonary arterial abnormalities was mild. Corticosteroid therapy resulted in rapid resolution of clinical and radiographic signs; thiacetarsamide therapy was then given without complications. This syndrome may not be recognized as heartworm-associated and may be confused with other disorders, some being associated with a poor prognosis and requiring different therapy.     

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.     

The Safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month follow-up, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse.     

Patent ductus arteriosus in an adult cat with pulmonary hypertension and right-sided congestive heart failure: hemodynamic evaluation and clinical outcome following ductal closure

Right-sided congestive heart failure (CHF) developed secondary to severe pulmonary hypertension (PH) in an 8-year-old cat with a left-to-right shunting patent ductus arteriosus (PDA). Vascular reactivity was tested prior to shunt ligation by treatment with oxygen and sildenafil. This treatment was associated with a significant decrease in pulmonary artery pressure as assessed by echocardiography. Subsequently surgical shunt ligation was planned. During thoracotomy, digital occlusion of the PDA was performed for 10 min with simultaneous catheter measurement of right ventricular pressure, which did not increase. Permanent shunt ligation resulted in a complete and sustained clinical recovery. A lung biopsy sample obtained during thoracotomy demonstrated histopathological arterial changes typical of PH. Cats can develop clinically severe PH and right-sided CHF secondary to a left-to-right PDA even at an advanced age. Assuming there is evidence of pulmonary reactivity, PDA occlusion might be tolerated and can potentially produce long-term clinical benefits.     

Acute pulmonary edema in a dog with severe pulmonary valve stenosis: A rare complication after balloon valvuloplasty

Pulmonic stenosis is a frequent congenital heart disease in dogs, and the treatment of choice is balloon valvuloplasty which is usually safe and successful. The authors describe for the first time a severe complication after balloon valvuloplasty in a five-month-old dog. After effective treatment, with a considerable drop in right ventricular pressures, the dog developed hypoxemia and dyspnea due to pulmonary edema. The dog underwent intensive care and symptoms improved after a few hours of oxygen therapy, continuous positive airway pressure, and furosemide. Although this event is rare, it could have a large impact on patient survival and should be considered in the treatment of severe pulmonary valve stenosis in the future.     

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.     

Complications following thiacetarsamide sodium therapy in Louisiana dogs with naturally-occurring heartworm disease

Four hundred and sixteen dogs with naturally-occurring heartworm disease were evaluated for complications following thiacetarsamide sodium therapy. Of these, 109 dogs (26.2%) experienced complications. Increased lung sounds was the most commonly seen complication, followed by fever and coughing. In dogs with complications, 83.5% of them presented without clinical evidence of pulmonary thromboembolism or heart failure. There were no statistically significant differences between the age, sex, breed and body size of dogs that experienced complications following thiacetarsamide therapy and dogs that did not. Complications were most frequently seen 5 to 9 days following thiacetarsamide therapy although some dogs experienced initial complications as late as 28 days. Thirty-three of 109 dogs (33.0%) with complications responded to exercise restriction. The remaining 76 dogs with complications prior to or following thiacetarsamide required adjunct drug therapy. Of these, 35 dogs responded favorably to anti-inflammatory doses of prednisolone or prednisone. Five dogs died or were euthanatized because of the complications experienced. Eighteen of 416 dogs (4.3%) presented with clinical evidence of pulmonary thromboembolism or heart failure prior to the thiacetarsamide therapy. All 18 dogs experienced complications in spite of adjunct drug therapy and exercise restriction prior to, during, and following thiacetarsamide therapy. Survival rate following resolution of the thiacetarsamide-induced complications was greater than 98%.     

Pulmonary vascular response of dogs with heartworm disease.

Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals.     

Non-cardiogenic pulmonary oedema complicating balloon valvuloplasty and stent angioplasty of severe pulmonary valve stenosis in four dogs

In dogs, balloon valvuloplasty is considered the treatment of choice for severe pulmonary valve stenosis, and this technique is currently performed routinely in specialist referral practices with low morbidity and mortality. Stent angioplasty has also been recently proposed as a viable treatment option. The present case series describes the clinical course of four dogs with severe pulmonary valve stenosis, treated with balloon valvuloplasty or stent angioplasty at four different institutions, which developed non-cardiogenic pulmonary oedema perioperatively after apparently successful dilation of the pulmonary valve. In three cases, there was evidence of some degree of pulmonary hypertension before ballooning. Despite intensive care, the complication proved fatal in three cases. Clinicians should therefore be aware of this life-threatening complication, previously undescribed in dogs.     

Rectal strictures in 19 dogs: 1997-2005

The etiologies for nonneoplastic rectal strictures in dogs included foreign bodies, postoperative formation, inflammatory disease, and congenital malformation. Sixteen of 19 dogs underwent balloon dilatation therapy, and 14 of these 16 dogs received intralesional triamcinolone injections. Following dilatation, clinical signs persisted in one dog, improved with continued medical therapy in five dogs, and resolved in nine dogs for the duration of their follow-up period (mean 18 months; median 12 months); one dog was lost to follow-up. Balloon dilatation and triamcinolone were parts of a treatment regimen that improved clinical signs in the majority of dogs diagnosed with nonneoplastic rectal strictures.     

Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines

Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

RADIOGRAPHIC FINDINGS DURING RECOVERY FROM DISCOSPONDYLITIS

The diagnosis of discospondylitis is based on radiographic changes in the vertebrae. The limitations of this method are the time gap between the onset of clinical signs and the first appearance of the radiographic findings, as well as the disassociation between the clinical and radiographic signs during recovery. It is known that the radiographic changes appear only two to four weeks after the onset of clinical signs, but the characteristics of radiographic changes during recovery has yet to be documented, thus making follow-up radiographs difficult to interpret. A prospective and retrospective study was designed to document typical radiographic changes during recovery from discospondylitis. We reviewed 12 dogs that had complete and uneventful recovery with antibiotic therapy alone. Periodic follow-up radiographs and clinical examinations were conducted up to five months after the onset of clinical signs to correlate between the clinical status and radiographic changes during recovery. Although the clinical signs improved within the first 10 days of antibiotic therapy, the radiographic deterioration continued before regression and signs of radiographic recovery were noticed. This radiographic deterioration, despite successful antibiotic therapy, appeared shorter in young dogs (less than one year old) and lasted three to nine weeks in older dogs.     

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.     

Radioiodide (131I) therapy for the treatment of canine thyroid carcinoma

OBJECTIVE: To assess the efficacy of radioactive iodine treatment (131I) for canine thyroid carcinoma, as both the sole therapeutic modality and as an adjunct to surgery. DESIGN: Retrospective analysis of case records from the Gladesville Veterinary Hospital Nuclear Medicine Service, Sydney, between August 1988 and December 2001. CASE DETAILS: The records of 65 dogs with thyroid carcinoma were analysed according to therapy and outcome. Forty-three dogs received radioiodide therapy, either as the sole therapeutic modality (32) or as an adjunct to surgery (11). Radioisotope therapy consisted of one to three doses of 131I with a dose range of 555 to 1850 MBq. For analysis, dogs were divided into groups according to therapy: no treatment, surgery alone, surgery with radioiodide therapy or radioiodide therapy alone. Mode of therapy, dosage of 131I, clinical staging and age were all independently analysed according to survival to compare efficacy or predictive value respectively. RESULTS: When radioiodide therapy was used as an adjunct to surgery, median survival was 34 months. Censored median survival time for dogs that received radioiodide alone was 30 months. Dogs that did not receive treatment had a median survival of only 3 months. Log rank statistical analysis indicated that mode of therapy was significantly correlated with survival but that clinical stage of disease was not. CONCLUSION: The authors conclude that 131I therapy is effective at extending survival time, both as a sole therapeutic modality and as an adjunct to surgery, in dogs with invasive canine thyroid carcinoma. Incomplete surgical resection may not prolong survival in dogs also receiving 131I therapy, however surgical resection with curative intent should be recommended as the first line of therapy for mobile thyroid carcinomas. Radioisotope therapy can be recommended for cases where surgery alone is considered unlikely to be curative because of metastatic disease or local invasion, or for cases where surgery has been attempted but complete surgical removal has not been achieved.     

Suspected air embolism associated with post-anesthetic pulmonary edema and neurologic sequelae in a horse

A 523 kg Quarter Horse was anesthetized for unilateral eye enucleation. The anesthetic period was unremarkable. During anesthetic recovery the cap on the jugular venous catheter became dislodged. Clinical signs of pulmonary edema associated with moderate arterial hypoxemia subsequently developed. Although pulmonary edema resolved with medical therapy, the day following anesthetic recovery, clinical signs of vestibular disease and blindness developed. Treatment included nasal oxygen insufflation, flunixin meglumine, furosemide, dexamethasone, thiamine, dimethylsulfoxide, antimicrobials, and phenylbutazone. The horse recovered and was discharged from the hospital after 7 days of treatment and was neurologically normal at 6 weeks. While venous air embolism was not confirmed in this case, the catheter cap complication followed by signs of pulmonary edema and neurologic sequelae support the presumptive pathogenesis of this horse's complications. Diagnostic confirmation of air embolism in horses with compatible acute clinical signs should be documented with echocardiography.