Plasma nitric oxide in dogs with pulmonary hypertension secondary or not to left-sided heart disease

Braz, J.B.; Beluque, T.; Ampuero, R.A.N.; Canola, R.A.M.; Batalhão, M..E.; Cárnio, E.C.; Camacho, A.A.

doi:10.1590/1678-4162-12528

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Veterinary Medicine and Technology and Inspection of Animal Products • Arq. Bras. Med. Vet. Zootec. 75 (2) • Mar-Apr 2023 • https://doi.org/10.1590/1678-4162-12528 copy

Plasma nitric oxide in dogs with pulmonary hypertension secondary or not to left-sided heart disease

[Óxido nítrico plasmático em cães com hipertensão pulmonar secundária ou não à doença cardíaca esquerda]

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Nitric oxide (NO) is an important mediator responsible for vasodilation in pulmonary hypertension (PH) in humans. Based on human literature, it is suggested that in dogs there is also NO production decrease in lung tissue in the presence of PH with hypoxia. Therefore, the aim of this research was to determine the indirect plasmatic NO concentration in dogs with PH secondary or not to the left-side heart disease (LHD) and also with low, intermediate and high probability of PH to characterize the NO involvement on PH in dogs. Blood samples were collected from 35 dogs with probability of PH to NO measurement. NO concentration was estimated by the nitrite/nitrate concentration, and it was significantly different (p=0.002) in dogs with PH secondary to LHD (median=14 µM, range 11.19-16.59) and not secondary to LHD (median=25.88µM, range 15.08-36.71). However, this was not significant for the probability of low, intermediate, and high PH, although there was a tendency for NO concentration to be higher in dogs with high PH. The results of this study demonstrate that there is release of NO in dogs with PH, as well as that its dosage could differentiate dogs with PH secondary to LHD from dogs with non-secondary PH.

Keywords:
hypoxia; nitrate; nitrite; pulmonary arterial pressure; pulmonary vasculature

Clinical variables	PH not secondary to LHD	PH secondary to LHD	P value*
N cases	17	18
Sex (male/female)	6/12	9/8	0.400
Age (years)	11 (10-13)	12 (11-13)	0.200
BW (kg)	7.4 (4.6-9.8)	8.6 (4.5-14)	0.488
NO (µM)	14 (11.19-16.59)	25.88 (15.08-36.71)	0.002
*P< 0.05. BW, body weight; NO, nitric oxide.

Clinical variables	Low probability	Intermediate probability	High probability	P value
N cases	12	9	14
Sex (male/female)	5/7	4/5	6/8	1
Age (years)	13 (8.75-12) ^b	13 (12.75-15.25) ^a	12 (10.25-13) ^ab	0.011
BW (kg)	8.75 (5.10-10.55)	7.40 (4-10.8)	7 (4.78-14.33)	0.835
NO (µM)	13.51 (12.35-25.85)	15.91 (15.22-19.02)	18.94 (14.25-29.08)	0.380

	PH not secondary to LHD	PH secondary to LHD	P value*
Echocardiographic left heart variables
LVIDDN	1.6(1.33-1.53)	1.82(1.6-2.17)	0.003
LVIDSN	0.77(0.68-0.85)	0.9(0.73-1.14)	0.033
EF (%)	78.62±7.42	78.99±7.36	0.886
FS (%)	46.24±8.02	47.17±6.93	0.717
LA/Ao ratio	1.51(1.29-1.66)	2.16(1.75-2.42)	0.000
E (m/s)	0.7±0.19	1.23±0.3	0.000
A (m/s)	0.77±0.28	1.09±0.24	0.002
E/A	0.755(0.755-1.105)	1.08(0.805-1.505)	0.171
Aortic flow velocity (m/s)	1.08±0.26	1.31±0.26	0.021
S' mitral (m/s)	0.94±0.32	1.1±0.32	0.171
E' mitral (m/s)	0.62±0.17	0.95±0.27	0.000
E/E' mitral	1.09(1.07-1.22)	1.41(1.15-1.72)	0.050
Echocardiographic right ventricle and pulmonary artery variables
TR (m/s)	2.99(0.46)	2.89(0.68)	0.642
PA/Ao ratio	0.92(0.82-0.99)	1.04(0.94-1.17)	0.027
AT/ET (pulm flow)	0.45(0.12)	0.36(0.11)	0.031
RPAD Index	34.14(9.93)	30.46(12.36)	0.344
TAPSE (mm/kg^0.284)	6.93(2.13)	6.74(1.74)	0.782
RVILD/kg^0.33	11.31(2.63)	13.03(2.45)	0.054
RVILS/kg^0.33	8.58(2.02)	11.19(2.38)	0.001
RVIDD_apical/kg^0.33	8.07(2.2)	8.62(2.67)	0.504
RVIDD_long/kg^0.33	5.01(4.28-5.97)	4.78(3.68-6.93)	0.895
RVAD (cm²/kg^0.62)	0.72(0.63-1.02)	0.93(0.65-1.03)	0.448
RA high/kg^0.33	9.5(1.81)	10.57(2.6)	0.165
RAA (cm²/kg^0.71)	0.66(0.57-0.81)	0.95(0.57-1.10)	0.269
RVFWD/LVFWD	0.77(0.18)	0.85(0.16)	0.155
RVIDD/LVIDD_long	0.44(0.34-0.52)	0.3(0.24-0.38)	0.009

Echocardiographic left heart variables
	Low probability	Intermediate probability	High probability	P value
LVIDDN	1.57(0.29)	1.7(0.48)	1.7(0.41)	0.647
LVIDSN	0.84(0.77-0.9)	0.85(0.69-1.12)	0.74(0.65-1.03)	0.930
EF (%)	78.6(76.38-80.21)	77.14(72.50-83.17)	80.27(71.85-86.96)	0.876
FS (%)	45.78(4.53)	45.42(7.3)	48.3(9.43)	0.588
LA/Ao ratio	1.66(0.43)	1.86(0.46)	1.98(0.53)	0.293
E (m/s)	0.82(0.35)	1.06(0.31)	1.11(0.53)	0.255
A (m/s)	0.86(0.35)	1.05(0.31)	0.92(0.26)	0.401
E/A	0.92(0.8-0.9)	0.77(0.72-0.9)	0.93(0.79-1.45)	0.269
Aortic flow velocity (m/s)	1.13(0.36)	1.26(0.14)	1.22(0.25)	0.641
S' mitral (m/s)	0.9(0.34)	1.08(0.27)	1.15(0.23)	0.132
E' mitral (m/s)	0.6(0.18)	0.79(0.13)	0.74(0.18)	0.063
E/E' mitral	1.22(1.07-1.54)	1.14(1.09-1.38)	1.26(1.1-1.68)	0.719
Echocardiographic right ventricle and pulmonary artery variables
TR (m/s)	2.51(0.33)^b	2.93(0.48)^ab	3.27(0.58)^a	0.004
PA/Ao ratio	0.95(0.83-1)	0.93(0.87-1)	1.07(0.93-1.22)	0.145
AT/ET (pulm flow)	0.43(0.1)^a	0.47(0.12)^ab	0.34(0.11)^b	0.023
RPAD Index	36.95(9.08)	33.02(11.38)	28.16(11.64)	0.130
TAPSE (mm/kg^0.284)	6.28(1.9)	7.02(1.89)	7.2(2)	0.465
RVILD/kg^0.33	12.62(2.49)	11.12(2.56)	12.72(2.75)	0.263
RVILS/kg^0.33	10.05(1.96)	8.77(2.32)	10.63(2.87)	0.172
RVIDD_apical/kg^0.33	6.68(1.84)^b	8.39(2.41)^ab	9.36(2.29)^a	0.029
RVIDD_long/kg^0.33	4.42(1.33)^b	4.28(1.14)^b	6.35(1.74)^a	0.002
RVAD (cm²/kg^0.62)	0.72(0.63-0.94)	0.7(0.64-1.00)	1.03(0.67-1.47)	0.168
RA high/kg^0.33	9.41(1.73)^ab	8.8(1.67)^b	11.45(2.3)^a	0.005
RAA (cm²/kg^0.71)	0.62(0.52-0.69)^b	0.58(0.51-1.10)^ab	0.97(0.74-1.27)^a	0.025
RVFWD/LVFWD	0.7(0.16)^b	0.86(0.17)^ab	0.87(0.15)^a	0.025
RVIDD/LVIDD_long	0.35(0.15)^ab	0.24(0.11)^b	0.5(0.12)^a	0.024

Universidade Federal de Minas Gerais, Escola de Veterinária Caixa Postal 567, 30123-970 Belo Horizonte MG - Brazil, Tel.: (55 31) 3409-2041, Tel.: (55 31) 3409-2042 - Belo Horizonte - MG - Brazil
E-mail: abmvz.artigo@gmail.com

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[1] Corresponding author: jaislanemedvet@gmail.com