Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate 2005-2014

Study Overview

Title:

Acute resolution of pulmonary alveolar infiltrates in dogs with pulmonary hypertension treated with sildenafil citrate (2005-2014)

Authors:

Heidi B. Kellihan, Kenneth R. Waller, Alyssa Pinkos, Howard Steinberg, Melissa L. Bates

Institutions:

University of Wisconsin, School of Veterinary Medicine & Department of Pediatrics.

Publication Date:

April 2015

Purpose:

The study aims to evaluate the effects of sildenafil on pulmonary hypertension (PH) and pulmonary infiltrates in dogs, investigating its potential to alleviate clinical symptoms and improve radiographic findings.

Keywords

  • Pulmonary Edema: A condition characterized by fluid accumulation in the lungs, which can result in breathing difficulties.

  • Pulmonary Infiltrate Score: A scoring system used to assess the severity of lung infiltrates as observed on radiographs.

  • Interstitial Pulmonary Fibrosis: A chronic lung condition involving progressive scarring and thickening of lung tissue, leading to decreased lung function.

  • Tricuspid Regurgitation: A valvular heart disease in which the tricuspid valve fails to close properly, resulting in backward flow of blood into the right atrium.

  • Quality of Life Score: A method of assessing the overall well-being and health status of animals, often involving owner-reported metrics.

Objective

The primary objective of this study was to describe clinical cases of dogs diagnosed with pulmonary hypertension and pulmonary infiltrates that were treated with sildenafil. The authors aimed to present measurable improvements in clinical parameters post-treatment.

Materials and Methods

Inclusion Criteria:

  • Recent heartworm testing to exclude heartworm disease as a contributing factor.

  • Required 3-view thoracic radiographs, both prior to (PRE) and after (POST) treatment.

  • Echocardiograms completed both PRE and POST.

  • A total of 10 dogs meeting these criteria were included in this retrospective analysis.

Clinical Score System:

The scoring system was based on clinical presentation, quantitatively rated from 0 (normal) to 2 (severe disease), combined with a quality of life assessment provided by the owners, also scaled from 0 to 2.

Thoracic Radiographs:

Radiographs were evaluated by a certified veterinary radiologist, scoring was based on a modified Murray Lung Injury Score standard to assess lung injury severity.

Echocardiographic Examination:

This was performed by board-certified veterinary cardiologists, focusing on measuring peak tricuspid regurgitation velocity, a reflection of right heart pressures.

Statistical Analysis:

Non-parametric methods were used due to the small sample size; the Wilcoxon signed rank test was applied to compare clinical parameters before and after the administration of sildenafil.

Results

  • Descriptive Characteristics: The median age of the dogs was 13 years, with a median weight of 5 kg, indicating older, smaller breeds were subjects of study. The most common presenting complaint was respiratory distress, identified in 9 out of 10 dogs.

  • Oxygen Therapy: Required in 7 out of 10 dogs prior to sildenafil treatment; however, there was no documented improvement with this intervention alone.

  • Clinical Scores Post Discharge: The median follow-up time was 9 days, providing a window to assess clinical outcomes.

Clinical Scores:

  • Median PRE score: 4 (range: 3-4) indicating significant clinical impairment.

  • Median POST score: 0 (range: 0-2), showing a statistically significant improvement (p = 0.005).

Pulmonary Infiltrate Score:

  • Median PRE score: 10 (range: 5-12), indicating severe infiltrates.

  • Median POST score: 4 (range: 0-6), showing a significant reduction in severity (p = 0.006).

Tricuspid Regurgitation Gradient:

  • Median PRE: 83 mmHg (range: 57-196) reflecting elevated pressures in the right heart.

  • Median POST: 55 mmHg (range: 33-151), with a significant decrease noted (p = 0.002).

Discussion

The findings demonstrated that dogs with pulmonary hypertension share common clinical signs, including exercise intolerance and respiratory distress. A unique observation from this study was the presence of patchy, rather than diffuse, pulmonary alveolar infiltrates, which may not be typically associated with pulmonary hypertension in veterinary medicine. The presence of patchy edema may result from factors like non-uniform pulmonary capillary perfusion, drawing parallels with High Altitude Pulmonary Edema (HAPE) observed in humans. Overall, treatment with sildenafil was shown to yield positive outcomes in both pulmonary hypertension and associated pulmonary infiltrates.

Limitations

  • Retrospective Nature: The absence of a control group of dogs not receiving sildenafil limits the study's ability to draw definitive conclusions about treatment efficacy.

  • Histopathological Data: Limited availability of definitive biopsy confirmation to ascertain underlying conditions; only a single dog underwent confirmed pathology workup.

  • Uncertainty in Diagnosis: The true prevalence of pulmonary infiltrates associated with pulmonary hypertension remains unclear.

Conclusions

The study concludes that pulmonary alveolar infiltrates can develop in dogs with pulmonary hypertension, often misdiagnosed as conditions such as pneumonia or congestive heart failure. Sildenafil citrate is effective in treating both pulmonary hypertension and associated clinical signs, highlighting the importance of recognizing and addressing pulmonary infiltrates in canine patients with pulmonary hypertension as they can respond favorably to sildenafil therapy.