Evaluation of the right ventricular function in dogs with brachycephalic syndrome before and after rhinoplasty

Daniel Carvalho Hainfellner1*, Mário dos Santos Filho1, Bruno Alberigi2, Alexandre José Rodrigues Bendas2, Carolina do Valle Aben Athar1, Nathalia Marques de Oliveira Lemos3, Karen Denise da Silva Macambira Barbosa3, Juliana Silva Do Carmo3, Ana Maria de Barros Soares4, Aguinaldo Francisco Mendes Junior5, Cristiano Chaves Pessoa da Veiga2, Daniel de Almeida Balthazar2 & Jonimar Pereira Paiva2 1Veterinarian, MSc, Programa de Pós-Graduação em Medicina Veterinária (PPGMV), Departamento de Medicina e Cirurgia Veterinária (DMCV), Instituto de Veterinária (IV), Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, RJ, Brazil 2Veterinarian DSc, DMCV, IV, UFRRJ, Seropédica, RJ, Brazil 3Veterinarian, Resident, Programa de Residência em Medicina Veterinária Cardiologia e Doenças Respiratórias de Animais de Companhia, DMCV, IV, UFRRJ, Seropédica, RJ, Brazil 4Veterinarian DSc, Centro de Ciências Médicas, Faculdade de Veterinária, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil 5Veterinarian MSc, Programa de Pós-Graduação em Medicina Veterinária – Clínica e Reprodução Animal, UFF, Niterói, RJ, Brazil


Introduction
Brachycephalic dogs commonly present with anatomical changes that lead to upper airway obstruction, causing a clinical syndrome known as brachycephalic syndrome (Dupré & Heidenreich, 2016;Meola, 2013;Oechtering, 2010). The increase in negative pressure and swirling of the airflow inside the airways occurs as a result of the chronic obstructive process, leading to a decrease in the patient's quality of life (Oechtering, 2010).
Arteriolar vasoconstriction and consequent pulmonary hypertension occur as a result of upper airway obstruction (Park & Troxler, 2002;Abd El-Moneim et al., 2009). This leads to an overload of the right heart chambers, and consequently the development of Cor pulmonale (Boon, 2011;Carvalho et al., 2002;Tilley, 2002). These changes can be identified by echodopplercardiography when the right ventricular function is assessed (Boon, 2011;Madron, 2016).
This study aimed to evaluate the repercussion of airway obstructions in the right heart chamber, from a morphofunctional point of view, by comparing the results of echocardiography evaluation before and after corrective surgery by laser rhinoplasty.

Material and methods
The project was submitted to the Ethics Committee on Animal Use of the Instituto de Veterinária da Universidade Federal Rural do Rio de Janeiro and was evaluated and approved under number 5490040118. Animals were included in the study after obtaining consent from their owners.
Animals with nostril stenosis from the clinical care of the veterinary hospital of Universidade Federal Rural do Rio de Janeiro were included, after pre-anesthetic evaluation consisting of physical examination, electrocardiography, chest radiography, complete blood count, and measurement of serum levels of alkaline phosphatase, alanine aminotransferase, BUN, and creatinine. Heartworm screening was performed using the modified Knott method (Newton & Wright, 1956) and circulating antigens of Dirofilaria immitis using the ELISA technique (Snap 4DX Plus®, IDEXX Laboratories, Inc., USA). Patients with cardiorespiratory or systemic diseases detected on clinical or complementary examinations were excluded from the study.
Echocardiography evaluation was performed using the Esaote MyLab Gamma® device (Genoa, Italy) with two sectoral transducers (1-4 MHz and 3-11 MHz). Echocardiography was performed according to the standards recommended by the Echocardiography Committee of the Specialty of Cardiology, American College of Veterinary Internal Medicine, with modifications suggested by Chetboul (2016).
The morphology and function of the left atrioventricular and aortic valves of the left cardiac chambers were also evaluated. In addition, the diastolic function was evaluated. Systolic function was evaluated in the M-mode using the Teicholz method. If any changes that could affect right ventricular function were detected, the animal was excluded from the study.
For the assessment of pulmonary flow, the viewing window was the left cranial parasternal view of the right ventricular outflow tract long axis, placing the recording zone within the pulmonary valve area. The maximum transpulmonary flow velocity (VmP) and the pressure gradient between the pulmonary artery and the right ventricle (GrP) were evaluated.
To evaluate the diastolic function of the RV, transtricuspid flow and the E/A ratio waves were evaluated, in addition to the E '/A' ratio waves using tissue Doppler of the free wall of the right ventricle close to the tricuspid ring. The E/A ratio waves in the transtricuspid flow and E '/ A' waves were considered normal when the values were between 1.12 and 1.80 (Madron, 2016).
On the day of the surgical correction of nostril stenosis, patients were directed to an airconditioned room at 20ºC and free from stressful stimuli. Morphine (1 mg/kg IV), propofol induction (3 mg/kg IV), and 1.5% isoflurane were used as pre-anesthetic medications.
Rhinoplasty was performed using the nostril wing correction technique and the removal of excess tissue from the nasal vestibular region. A carbon infrared diode laser (Vetlaser®, Brazil) with a wavelength of 808 nm ± 10 nm and useful power of 9 W ± 20%, with 400 µm or 600 µm diameter fiber was used. After completion of the procedure, dexamethasone (1 mg/animal/ IV) was administered, and the animals were released after complete recovery from anesthesia.
The Kolmogorov-Smirnov test was used to analyze the normal distribution of the data. The student's t-test was used to analyze the normal data with repeated measures. The data that did not present a normal distribution were analyzed using the Friedman test in order to verify possible significant statistical differences between the rankings (values) at different moments of the treatment. A significance level of 5% was considered. SPSS®IBM program version 26.0 was used.

Results
Sixteen dogs were included in the study. Of the 16 dogs, 25% (n = 4) were of the Pug breed and 75% (n = 12) were French Bulldogs. Of these, 56.3% (n = 9) were male and 43.7% (n = 7) were female. The average age of the animals included in the study was 1.7 ± 1.3 years old.
The assessment of the ability of the right ventricle to pump blood for systemic circulation adequately (systolic function), showed that the mean values of TAPSE on days 0 ( ̅ = 9.8 mm), 30 ( ̅ = 10.7 mm), and 60 ( ̅ 11, 9 mm) were similar (Fr = 2,774; p = 0.250). A difference was observed in the values of FAC between days 0 ( ̅ = 59.6%) and day 60 (   When the capacity of the right ventricle to relax, allowing ventricular filling (diastolic function), was assessed, the mean values of the E/A ratio were similar, being 1.30 on day 0; 1.20 on day 30; and 1.28 on day 60 (Table 1). A similarity was observed in the evaluation of the E' / A' ratio, which was 1.3 on day 0; 1.2 on day 30, and 1.8 on day 60 (Table 1).
In the assessment of blood pumped from the right ventricle through the pulmonary artery (pulmonary flow), when the VmP was compared, a difference was observed between day 0 and day 30 (t = 1.8971; p = 0.0386) and between day 0 and day 60 (t = 1.9855; p = 0.0328), with no difference between days 30 and 60 (t = 0.1742; p = 0.432). When assessing the GrP, a difference was observed between day 0 and day 30 (t = 2.267; p = 0.0193) and day 0 and day 60 (t = 2.2406; p= 0.0203), and as observed with VmP, there was no difference between day 30 and day 60 (t = 0.083; p = 0.4672).

Discussion
Among the animals included in the study, no difference was observed in the systolic function of the right ventricle when assessed using TAPSE and by the S-wave velocity. It was inferred from these results that right ventricular overload was not detected by these methods before surgery. It is noteworthy that the mean age of the animals included in the study (1.7 ± 1.3 years) may also represent the fact that the sensitivity of these evaluations increases with chronicity and progression of cor pulmonale (Lira-Filho et al., 2009). Nonetheless, the FAC proved to be sensitive when detecting differences between day 0 and day 60. It was observed that on day 0, the myocardium presented values above expectations, which normalized 60 days later. This phenomenon could be due to the correction of the upper airway obstructions, which tend to reduce pulmonary vasoconstriction and, consequently, pulmonary vascular resistance. These events ultimately reduce the effort that the right ventricle needs to exert (Abd El-Moneim et al., 2009).
A study correlating the right ventricular end-diastolic area (RVEDA) suggested that it is a more accurate assessment of the right ventricular overload (Vezzosi et al., 2018) since TAPSE and FAC results are controversial in the literature (Pariaut et al., 2012;Tidholm et al., 2015;Visser et al., 2016;Poser et al., 2017). Although this assessment was not performed in the present study, it is possible that it will not demonstrate significant results. This is because Vezzosi et al. (2018) showed that the statistical correlation of this measure was only positive in animals with moderate-to-severe pulmonary hypertension. However, the animals evaluated in the present study did not show signs of moderate or severe pulmonary hypertension.
Although the occurrence of diastolic dysfunction of the right ventricle in dogs with upper airway obstruction disease is not yet well defined, in the present study, the animals were normal before and after surgery. This indicates that the respiratory changes in the studied dogs had no significant impact. However, as discussed in the results of the right ventricular systolic function, the sample of young animals may have influenced this result, since the chronicity of obstructive processes can culminate in chronic pulmonary changes and consequent cor pulmonale and diastolic dysfunction (Abd El-Moneim et al., 2009;Kim, 2018;Koc et al., 2012;Park & Troxler, 2002) The evaluation of VmP and GrP in the present study showed that there was an increase in these parameters after surgical correction of respiratory changes. This finding reinforces the results of the evaluation of the FAC, where an increase in pulmonary vascular resistance secondary to upper airway obstruction, even without the development of pulmonary hypertension, caused an increase in pulmonary resistance, leading to greater resistance to blood pumping through the right ventricle (Pyle et al., 2004). Thus, after the improvement of pulmonary hypoxia, and consequently a decrease in afterload, there is less pulmonary resistance, improving the speed and pressure gradient of the pulmonary flow (Abd El-Moneim et al., 2009).
Knowing that the development of pulmonary vascular lesions related to cor pulmonale and mainly to brachycephalic syndrome is slow and chronic (Canola et al., 2018), the age of the animals and the short study period may have been crucial for the non-observation of other changes in the assessment indexes of the right ventricle. Therefore, further studies in this area are recommended.

Conclusion
The present study suggests that in the dogs evaluated, nostril stenosis contributed to right heart overload since after correction of this alteration, the values of the presented right ventricular fractional area and the velocity and pressure gradient of pulmonary arterial flow improved.