Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

K Williams,A Cartoceti,D Goldsmith,S French,S L Priestnall,K Andrie,A Jutkowitz,D Wilson,S Jennings

doi:10.1177/0300985815626572

Abstract

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

Highlights

Pulmonary hypertension is a clinical diagnosis established through the documentation of pulmonary arterial (PA) pressures above established normal values
Pulmonary veno-occlusive disease was first reported in human medicine in after a 48-year-old baker in Germany died from a progressive respiratory disease characterized by dyspnea, pulmonary edema, and cyanosis
As in human pulmonary veno-occlusive disease (PVOD), pulmonary arterial medial hypertrophy and intimal thickening were relatively common in smallto medium-sized PA in canine PVOD

Summary

Introduction

Pulmonary hypertension is a clinical diagnosis established through the documentation of pulmonary arterial (PA) pressures above established normal values. In part because of the frequency of PA lesions in PVOD, both PVOD and PCH have been classified together as a subgroup of PAH in the most recent clinical classification of PH in humans.[38] In veterinary medicine, there remains a poor understanding of the breadth of causes of pulmonary hypertension and the spectrum of vascular remodeling associated with the disease.[16] Unlike in human medicine, pulmonary arterial catheterization is rarely performed to measure PA pressures in dogs; instead, such pressures are estimated using Doppler echocardiography to measure tricuspid valve regurgitation velocity as a proxy for direct measurement of PA pressures.[13,29,35,36] PAH is most often recognized in dogs as a sequela to congestive heart failure and PVH in small breed dogs with chronic mitral valve disease, secondary to heartworm infection, or associated with chronic interstitial lung disease.[15,34,39,41] Idiopathic PAH (iPAH) is recognized clinically in dogs. We describe the gross and histologic findings in 11 dogs that died from primary pulmonary disease, with similar lesions as PVOD in humans

Methods

Results

Conclusion