Investigation of red blood cell and platelet indices in adult dogs suffered from myxomatous mitral valve disease with and without pulmonary hypertension.

Background: Pulmonary hypertension (PH) is a common complication of cardiopulmonary disease. In dogs, PH commonly occurs secondary to myxomatous mitral valve disease (MMVD). Red blood cell and platelet indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), mean platelet volume (MPV) and platelet distribution width (PDW), have previously been found to be indicators for predicting and prognosing PH in humans. Therefore, this study aimed to investigate whether these indices are associated with MMVD and/or PH in dogs. Methods: Two hundred and forty-six dogs were retrospectively recruited for the study and classified into 4 groups: normal (n = 49), MMVD (n =102), PH (n =17), MMVD+PH (n =78). A sub-analysis was performed in dogs with MMVD without evidence of PH according to stage B1 (n =20), stage B2 (n =15), stage C (n =67). The data are expressed as median (interquartile range). Results and discussion: No significant differences (p < 0.05) were found in MCV, RDW and MPV among all groups (normal, MMVD, PH and MMVD+PH). However, decreases in MCH and MCHC were found in MMVD [22.40 (20.90-23.50) pg and 35.25 (33.08-36.90) g/dL], MMVD+PH [22.25 (20.85-23.98) pg and 35.65 (33.30-37.33) g/dL] and PH groups [21.20 (20.60-22.20) pg and 33.80 (32.75-35.70) g/dL] compared to the normal dogs [24.29 (23.55-24.90) pg and 38.20 (37.50-39.05) g/dL] (p < 0.001). Decreases in PDW were found in dogs in the MMVD+PH [15.10 (14.98-15.30) %] groups compared to dogs in the normal group [15.30 (15.10-15.50) %] (p = 0.004). Sub-analysis of MMVD dogs without PH showed a decrease in MCH in dogs with stage B2 MMVD [21.00 (20.50-22.90) pg] and stage C MMVD [22.40 (20.90-23.20) pg] compared to normal dogs [24.29 (23.55-24.90) pg] (p < 0.001). MCHC of dogs with stage B1 [36.55 (33.53-37.78) g/dL] (p = 0.004), B2 [32.90 (32.00-35.00) g/dL] (p < 0.001) and C MMVD [35.30 (33.30-36.80) g/dL] (p < 0.001) were lower than those of normal dogs [38.20 (37.50-39.05) g/dL]. PDW in the stage C MMVD group [15.10 (15.00-15.30) %] was reduced compared to the normal group [15.30 (15.10-15.50) %] (p = 0.042) and the stage B1 MMVD group [15.35 (15.23-15.68) %] (p = 0.002). MCH, MCHC and PDW were negatively correlated with the left atrial and left ventricular size. Conclusion: Decreases in MCH and MCHC are related to MMVD, precapillary PH and postcapillary PH while PDW are associated with MMVD severity but not with the presence of PH.

Investigation of Genes and Proteins Expression Associating Serotonin Signaling Pathway in Lung and Pulmonary Artery Tissues of Dogs with Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease: The Preliminary Study.

Pulmonary hypertension (PH) is defined as an increase in pulmonary vascular pressure. It is one of the most common complications that occur as a result of degenerative mitral valve disease (DMVD) in dogs. Serotonin (5-HT) can trigger the development of PH. Accordingly, this study investigated the changes in the expression of genes and proteins associated with local 5-HT signaling in the lungs and pulmonary arteries (PA) of dogs with PH secondary to DMVD. Lung and PA tissue samples were collected from the cadavers of fourteen small-breed dogs and divided into normal (n = 4), DMVD (n = 5) and DMVD with PH (n = 5) groups. Gene expression (tph1, slc6a4 and htr2a) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of proteins (TPH-1, SERT, 5-HTR2A, ERK1/2 and pERK1/2) was examined by Western blot analysis and immunohistochemical staining. The results showed that the expression of genes and proteins evaluated by qRT-PCR and Western blot analysis in lung and PA tissues did not differ among groups. However, the expression of proteins related to 5-HT signaling tended to be upregulated in PA tissues from DMVD dogs with and without PH. Immunohistochemical examination revealed the overexpression of these proteins in the DMVD and DMVD with PH groups in lung tissue. These findings suggest a local effect of 5-HT signaling in DMVD dogs with and without PH.

Assessment of Platelet and Plasma Serotonin in Canine Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease.

Background: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD), the most common cardiovascular disease in dogs. Serotonin has been suspected to play a role in the pathogenesis of PH, so this study aimed to investigate the differences in platelet and plasma serotonin between normal, DMVD and DMVD with PH (DMVD+PH) dogs. Materials and Methods: Sixty-two small-breed dogs were enrolled to the study and divided into the normal (n = 22), DMVD (n = 20), and DMVD+PH (n = 20) groups. The platelet and plasma serotonin concentrations were measured by the competitive ELISA. Results: The Kruskal-Wallis revealed the difference among the four groups of normal (179.73 [102.37-352.24] ng/109 platelets), DMVD (325.99 [96.84-407.66] ng/109 platelets), DMVD with intermediate probability of PH (291.11 [106.69-400.84] ng/109 platelets) and DMVD with high probability of PH (35.82 [2.69-126.35] ng/109 platelets) (p = 0.014). The Dunn's post-hoc test showed a decrease in the platelet serotonin concentration of the DMVD dogs with high probability of PH compared to the DMVD group (p = 0.008). The plasma serotonin concentration was not different between normal, DMVD, and DMVD+PH dogs. Conclusion: In conclusion, a decrease in platelet serotonin concentration, which is associated with a degree of PH probability was found in DMVD dogs with PH. Further studies investigating roles of platelet serotonin in PH secondary to DMVD should be performed.