Pre- and postcapillary pulmonary hypertension in dogs: Circulating biomarkers

Abstract

Background: Pulmonary hypertension (PH) in dogs is a syndrome that could be primary or secondary due to pulmonary disease, pulmonary thromboembolism, heartworm disease, and heart failure. Due to the inability of right heart catheterization in veterinary patients, there is a lack of differential criteria between PH forms. In some acute cases, it is impossible to provide a full EchoCG or catheterization study. In this situation, circulating markers may be useful to discover the possible mechanism of PH form and provide specific therapy.
Aim: Following all previous data in human and veterinary studies, we assumed that plasm concentration of serotonin, endothelin-1 (ET-1), and vascular endothelial growth factor D (VEGF-D) would show a predominance in affected part of pulmonary circulation.
Methods: We studied 59 small-breed dogs of different sexes and ages. Groups were formed according to a primary pathology: healthy dogs (n = 8); dogs with myxomatous mitral valve disease (MMVD) and postcapillary PH (PostPH, n = 23); dogs with MMVD and precapillary PH (PrePH, n = 28). Animals in the study were diagnosed with the primary disease by standard echocardiographic methods and algorithms. Blood samples were collected at the moment of presentation and frozen in a −80°C fridge. For biochemistry analysis, we used species-specific ELISA kits, provided by Cloud-Clone Corp. (USA). The tests were provided by the means of Almazov National Medical Research Center, IEM laboratory.
Results: Dogs with EchoCG-proved PostPH had a higher concentration of VEGF-D in comparison to control and PrePH (р <0.001, for both). There was no difference between the control and PrePH groups (р >0.05). ET-1 was higher in PrePH in comparison to PostPH and control dogs (р <0.001, for both). In addition, there was no difference between the control and PostPH groups (р >0.05). Serotonin concertation did not have a difference between controls and PostPH. However, it was higher in PrePH than in control (р <0.033) and PostPH group (р <0.006). Receiver operating curve analysis showed that plasma concentrations of ET-1 (0.99) and VEGF-D (0.92) had high effectiveness in the differentiation of PostPH and PrePH.
Conclusion: This study showed a correlation between circulating biomarkers (serotonin, ET-1, and VEGF-D). We found a connection between ET-1 and right-sided heart failure as well as VEGF-D and left heart failure in the PH context.