Pulmonary Veno-occlusive Disease and Pulmonary Hypertension in Dogs: Striking Similarities to the Human Condition.

Abstract

Pulmonary hypertension (PH) in both humans and animals remains an enigmatic problem. PH in all species can occur idiopathically or can be associated with a wide variety of disease conditions. As such, PH has been grouped into various classes and most recently into 5 distinct categories at the 2013 World Congress on Pulmonary Hypertension in Nice. All forms of chronic PH involve pulmonary vascular remodeling that can be characterized by a predominance of pulmonary arterial remodeling, vein remodeling, or a variable contribution of both. In idiopathic pulmonary arterial hypertension (iPAH), the pulmonary vascular remodeling affects largely the precapillary arteries; on the other hand, in venous PH, including pulmonary veno-occlusive disease (PVOD) and PH due to left heart dysfunction, venous remodeling predominates but is often accompanied by pulmonary arterial changes. In fact, these can be pronounced, to an extent exceeding that seen in precapillary PH. Importantly, it is increasingly appreciated that most forms of PH, including those caused by hypoxia, interstitial lung disease, thromboembolism, and connective tissue diseases, may involve both arterial and venous remodeling. Unfortunately, in humans and animals, precise descriptions and documentation of pulmonary vein remodeling are still lacking in most of these conditions, and in animals, there have been no reports of PVOD causing severe PH and death. In this issue of the journal, Williams et al provide what appears to be the first description of a condition in adult dogs that shares many of the pathologic and clinical features of PVOD that are observed in humans. There were significant consistencies in these dogs with the human condition with regard to clinical presentation, radiologic findings, and lung pathology. Similar to humans with PVOD, almost all of the affected dogs presented with dyspnea, exercise limitation, fatigue, and syncope. The dogs reported in these studies all exhibited respiratory distress in the context of what was ultimately shown to be severe pulmonary arterial hypertension (PAH). Also, similar to humans, progressive worsening of clinical signs was observed. PVOD can manifest acutely, and presentation with sudden death has been described as is the case with dogs. Again, similar to humans, it is difficult to distinguish PVOD from PAH on clinical grounds alone since the clinical signs, as in humans, can be similar if not identical. Therefore, other studies need to be done to confirm the diagnosis. Echocardiography, which is always performed in human patients presenting with these findings, demonstrated evidence for increased pulmonary artery pressure as estimated by the velocity of the resurgent jet of flow through the tricuspid valve. It should of course be mentioned that in humans, false positives using this approach are common, and a formal diagnosis of PH requires confirmation by right heart catheterization, although this is probably not possible to perform routinely in animals. Radiologic studies are also helpful in establishing the diagnosis of PVOD. In humans, PVOD is suspected based on radiologic findings showing a combination of pulmonary artery enlargement, features of postcapillary congestion, and a normal-size left atrium. Septal Kerley B-lines in a subplural distribution, interstitial edema, and plural effusions are the principal plain chest radiographic clues to a postcapillary location of vascular obstruction. A diffuse alveolar pulmonary edema pattern is an additional important finding. These findings again seem to be largely recapitulated in dogs presenting with PVOD and PH. PVOD is a fibrotic disease process that predominately involves venules, small veins, and the veins in interlobular septa (ie, invaginations of pleural connective tissue demarcating up to 20 primary lobules of alveolar tissue), usually with relative sparing of the large veins of the hilum. The walls of affected small pulmonary veins show variable occlusive intima lesions and media thickening as a result of a disorganized smooth muscle hypertrophy and collagen matrix