Podcasts

Join Now

Treating pulmonary hypertension with Viagra | VETgirl Veterinary CE Podcasts

Need Help?

In today’s VETgirl online veterinary continuing education podcast, we review pulmonary hypertension (often called cor pulmonale) and the use of sildenafil (more famously known as Viagra). Pulmonary hypertension is classified is as an increase in either pre-capillary (pulmonary arterial ) or post-capillary (pulmonary venous) pulmonary resistance. In dogs, the disease occurs most commonly in older, small breed dogs as a result of chronic lung disease, chronic left-sided heart disease, heartworm infection, pulmonary thromboembolism, or left-to-right cardiac shunts (which is one of the reasons why it’s so important that you treat underlying lung disease before it progresses to pulmonary hypertension!). The clinical signs of pulmonary hypertension may be indistinguishable from primary respiratory disease or congestive heart failure and includ tachypnea, cyanosis, dyspnea, increased respiratory effort, syncope, etc. Definitive diagnosis of pulmonary hypertension is made via echocardiogram by estimation of pulmonary artery pressures (typically, a dog needs to have tricuspid regurgitation to have this measured on echo). Thoracic radiographs remain an important component to the medical workup in these patients (usually performed prior to echocardiography).

Pulmonary alveolar infiltrates can occur in humans with pulmonary hypertension but are not well described in canines. Such infiltrates in dogs are traditionally more readily recognized with congestive heart failure, pneumonia, hemorrhage, or non-cardiogenic pulmonary edema. In humans, these infiltrates associated with pulmonary hypertension can resolve with sildenafil therapy. So, Kellihan et al out of University of Wisconsin-Madison wanted to evaluate if similar resolution has been observed in treatment of canine patients with pulmonary hypertension and alveolar pulmonary infiltrates. They performed a retrospective study “Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014” and found 10 dogs that fit the inclusion criteria. All dogs were heartworm negative, and had evidence of pulmonary hypertension confirmed via echocardiogram.

In this study, they had three classifications of pulmonary hypertension:

Mild: estimated sPAP: 30-50 mm Hg
Moderate: estimated sPAP: 50-75 mm Hg
Severe: estimated sPAP: >75 mm Hg

Dogs also received a clinical score between 0 and 4 (with 0 representing no clinical signs and 4 representing significant overt clinical signs in combined opinion of the clinician and pet owner) and pulmonary infiltrate score. This pulmonary infiltrate score is based on a human score called the Murray Lung Injury Score. In simplest terms, the lung fields are divided into four quadrants, with a score of 0-4 given per quadrant and then combined for total score. With this lung injury score, 0 represents no alveolar infiltrate, while 4 represents severe alveolar infiltrates. The maximum lung score (indicating the most severe) score is 16.

Overall, the median age of dog was 13 years of age with a median weight of 5 kg. 70% (7/10) of the dogs were treated with furosemide prior to referral with no clinical improvement, and 40% (4/10) were treated with antibiotics prior to referral (with no clinical improvement). 70% (7/10) of the dogs required oxygen on presentation with minimal improvement with oxygen alone. In this study, the most common clinical signs in the dogs included respiratory distress, syncope, and cough; on physical exam, many of the dogs had systolic heart murmurs, pulmonary crackles, or cyanosis on presentation. None of the dogs had significant left-sided heart enlargement echocardiographically. Following the diagnosis of pulmonary hypertension, all of the dogs were treated with sildenafil (with a median dose of 1 mg/kg PO q 8h). No other medications were administered thereafter.

So, what’d they find in this study? Overall, there were significant reductions in pre versus post-sildenafil results for respiratory rate (median PRE: 100, median POST: 40), clinical score (median PRE: 4, median POST: 0), pulmonary infiltrate score (median PRE: 10, median POST: 4) and systolic pulmonary artery pressure (median PRE: 83, median POST: 55).

None of the patients in the study had radiographic findings to support the presence of congestive heart failure, pneumonia or hemorrhage, or a clinical history supportive of a cause for noncardiogenic pulmonary edema (such as seizures, strangulation, airway obstruction, etc.). One hypothesis for the development of patchy pulmonary alveolar infiltrates in these patients is a mechanism similar to that which occurs in humans/animals with high-altitude pulmonary edema (HAPE), which occurs at altitudes at > 2500 meters. The mechanism for high-altitude pulmonary edema is complex but the key pathophysiologic component involves heterogenous pulmonary capillary bed perfusion due to variable degree of pulmonary capillary vasoconstriction in response to hypoxemia. Capillary beds experiencing significant vasoconstriction divert blood towards those experiencing less constriction, increasing blood flow and hydrostatic pressure in those regions and potentially alveolar flooding thereafter.

So, how does Viagra help here? The potential mechanism for sildenafil’s beneficial properties in resolving this infiltrate/edema would therefore be a more even distribution of blood flow across the capillary bed by reducing pulmonary vasoconstriction. Note: sildenafil causes pulmonary artery vasodilation via phosphodiesterase inhibition and resultant increased cGMP production. The above described mechanism is also the proposed reason for the patchy nature of the infiltrates noted, as opposed to more diffuse infiltrates/edema typically noted with cardiogenic (CHF) or noncardiogenic pulmonary edema. Dogs in this study not only displayed improved respiratory and echocardiographic parameters, but also experienced improvement or resolution of pulmonary infiltrate.

The study is interesting and proposes a specific mechanism for pulmonary infiltrate in canine pulmonary hypertension patients, as well as a mechanism by which sildenafil monotherapy may resolve these infiltrates. The study is very small, however, and although the authors report that none of the patients showed improvement with furosemide or antibiotics given by referring veterinarians prior to arrival at the tertiary facility, we were not provided with a time scale of the average number of days prior to referral. Thus, although their clinical conclusions is almost certainly correct (i.e., none of these patients had pneumonia or CHF), we cannot ignore a confounding factor of these prior treatments. Furthermore, given the mechanism for the infiltrates proposed (similar to high altitude pulmonary edema), furosemide could potentially have a positive impact on infiltrates caused by regional increases in pulmonary hydrostatic pressure and alveolar flooding. I think their conclusions may truly prove to be valid, but a prospective study using exclusive sildenafil monotherapy is the only appropriate way to draw such a conclusion definitively going forward. Also, if the conclusion ultimately reached is that no therapy other than sildenafil is necessary in these cases, the clinical application of this conclusion may be more difficult in practice as radiographic “patchy pulmonary alveolar infiltrates” may not be so readily distinguishable from bronchointerstitial pulmonary changes in patients with pulmonary hypertension secondary to inflammatory lung disease (who may prove to require corticosteroid therapy in addition to sildenafil).

So, what do we take from this VETgirl podcast? Patchy alveolar pulmonary infiltrates in dogs with pulmonary hypertension (not associated with CHF) may occur secondary to heterogenous pulmonary capillary bed perfusion associated with hypoxic pulmonary vasoconstriction. Resolution of these infiltrates has been documented in association with sildenafil therapy, potentially due to reduced pulmonary vasoconstriction and more homogenous pulmonary blood flow. So, when in doubt, don’t be hesistant to reach for Viagra in those patients that you suspect have pulmonary hypertension!

References:
Kellihan HB, Waller KR, Pinkos A, et al. Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014. J Vet Cardiol 2015;17:182-191.

Abbreviations:
sPAP: systolic pulmonary artery pressure
CHF: congestive heart failure
HAPE: high altitude pulmonary edema
cGMP: cyclic guanosine monophosphate

Only VETgirl members can leave comments. Sign In or Join VETgirl now!