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Acute phase proteins and markers of oxidative stress to assess the severity of the pulmonary hypertension in heartworminfected dogs

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From 15th American Heartworm Society Triennial Symposium. New Orleans, LA, USA. September 11-13, 2016

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Acute phase proteins and markers of oxidative stress to assess the severity of the pulmonary hypertension in heartworminfected dogs

Author: Carretón Gomez, Elena,Cerón Madrigal, José Joaquín,Martínez-Subiela, Silvia,Tvarijonaviciute, Asta,Caro Vadillo, Alicia,Montoya Alonso, José Alberto
Year: 2017
DOI: 10.1186/s13071-017-2426-8
Source: https://accedacris.ulpgc.es/jspui/bitstream/10553/45338/1/Acute_phase_proteins.pdf
RESEARCH Open Access
Acu e phase p o eins and ma ke s o
oxida i e s ess o assess he se e i y o he
pulmona y hype ension in hea wo m-
in ec ed dogs
Elena Ca e ón
1*
, José Joaquín Ce ón
2
, Sil ia Ma ínez-Subiela
2
, As a T a ijona iciu e
2
, Alicia Ca o-Vadillo
3
and José Albe o Mon oya-Alonso
1
F om 15 h Ame ican Hea wo m Socie y T iennial Symposium
New O leans, LA, USA. Sep embe 11-13, 2016
Abs ac
Backg ound: Canine hea wo m in ec ion is cha ac e ized by pulmona y enda e i is and pulmona y hype ension
(PH). The aim o he p esen s udy was o e alua e he ela ionship be ween PH wi h he concen a ions o di e en
posi i e (C- eac i e p o ein [CRP] and hap oglobin [Hp]) and nega i e (albumin and pa aoxonase-1 [PON-1]) acu e
phase p o eins (APP), as well as he oxida i e s ess, by measu ing glu a hione pe oxidase (GPx) and o al an ioxidan
capaci y (TAC) in 27 hea wo m-in ec ed dogs on Day 0 (diagnosis) and Day 120 (1 mon h a e he las adul icide
injec ion). P esence/absence o PH was de e mined by he Righ Pulmona y A e y Dis ensibili y (RPAD) Index.
Resul s: On Day 0, 62.9% o he dogs showed PH. Concen a ions o CRP and Hp we e highe in dogs wi h PH,
especially in dogs wi h mode a e-se e e PH (P<0.005andP< 0.05, espec i ely). Albumin and PON-1 concen a ions
we e highe in dogs wi hou PH (P< 0.05 o albumin). On Day 120, 59.2% o he dogs p esen ed wi h PH; CRP
dec eased while Hp inc eased (P<0.005andP< 0.05, espec i ely). Also, albumin and PON-1 ose, especially in
absence o PH. The e we e no signi ican changes in he se um alues o GPx and TAC.
Conclusions: CRP and Hp ha e a po en ial p ognos ic ole in dogs wi h di o ila iasis because inc eases in posi i e APP
co ela ed wi h p esence and se e i y o PH. CRP dec eased, bu Hp pe sis ed a an ele a ed le el in dogs wi h PH
1 mon h a e he end o he adul icide ea men . CRP and Hp could wo k as ea ly bioma ke s o PH and be use ul o
s age he disease and o moni o he e olu ion o he pa ien and indi ec ly e alua e he pe sis ence o a e ial
damage a e he pa asi es ha e been elimina ed. Albumin and PON-1 also showed po en ial alue as ma ke s o PH,
al hough u he esea ch is necessa y o de e mine i s u ili y.
Keywo ds: Hea wo m, Di o ila ia immi is, Pulmona y hype ension, Pulmona y a e y, Enda e i is, Acu e phase
p o eins, In lamma ion, Oxida i e s ess, Canine
* Co espondence: [email p o ec ed]
1
Facul y o Ve e ina y Medicine, Resea ch Ins i u e o Biomedical and Heal h
Sciences (IUIBS), Uni e si y o Las Palmas de G an Cana ia, T asmon aña s/n,
35413-A ucas, Las Palmas, G an Cana ia, Spain
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The Au ho (s) Pa asi es & Vec o s 2017, 10(Suppl 2):477
DOI 10.1186/s13071-017-2426-8
Backg ound
Canine hea wo m disease is a ch onic disease caused by
Di o ila ia immi is and is cha ac e ized by he p esence o
he adul pa asi es in he pulmona y a e ies. The wo ms
cause p oli e a i e enda e i is om he i s days a e
hey each he caudal pulmona y a e ies. This damage
causes ch onic ascula emodeling ha leads o he de-
elopmen o pulmona y hype ension (PH), which can in-
duce igh -sided conges i e hea ailu e [1, 2]. This
pa hogenic eac ion is caused by he hos ’s esponse o he
wo m as well as he bac e ial endosymbion Wolbachia
pipien is, which igge s he elease o p oin lamma o y
and chemo ac ic cy okines, inducing cellula in il a ion
and ampli ica ion o he in lamma o y esponse [3, 4].
T ans ho acic Dopple echoca diog aphy is he
me hod o choice o diagnose na u ally occu ing PH in
e e ina y pa ien s [5]. Bu when icuspid egu gi a ion
and/o pulmona y insu iciency a e no p esen , he
diagnosis o PH is based on indi ec and subjec i e pa-
ame e s, which only help pa ially o quan i y he dis-
ease se e i y. Recen ly, he Righ Pulmona y A e y
Dis ensibili y Index (RPAD Index), which is calcula ed as
he di e ence in diame e o he igh pulmona y a e y
in sys ole and dias ole as measu ed by M-mode, was al-
ida ed as a aluable me hod o es ima e he p esence
and se e i y o PH in hea wo m-in ec ed dogs [6].
Acu e phase p o eins (APP) a e p o eins p esen in he
plasma whose concen a ions modi y in esponse o
auma, in ec ion o in lamma ion. APP a e conside ed
pa o he inna e hos de ense sys em, and i s quan i ica-
ion p o ides aluable clinical in o ma ion in he diagno-
sis, moni o ing and p ognosis o a ious diseases [7, 8].
The APP a e classi ied in o wo g oups based on hei e-
sponse o he igge ing e en : nega i e APP (eg, albumin
and pa aoxonase-1 [PON-1]) a e hose whose le els a e
diminished and posi i e APP (eg, C- eac i e p o ein
[CRP] and hap oglobin [Hp]) a e hose whose le els a e
inc eased when he e is an acu e phase esponse [9–11].
P e ious s udies ha e epo ed an acu e phase e-
sponse in dogs wi h D. immi is, cha ac e ized by a ia-
ions o APP wi h inc eases in CRP, dec eases in
albumin and PON-1 and a di e gence in he beha io
be ween CRP and Hp [12]. Fu he mo e, a s udy moni-
o ed he p og ession o he disease h ough he de e -
mina ion o he APP a e p e ea men wi h doxycycline
and i e mec in and a e he adul icide ea men wi h
mela somine by showing an imp o emen in he con-
cen a ions o APP as he pa hology disappea ed [13].
Ac i i y o an ioxidan enzymes, such as glu a hione
pe oxidase (GPx), has been quan i ied in plasma as mea-
su es o an ioxidan capabili ies. S udies ound ha GPx
de iciency was associa ed wi h endo helial dys unc ion
and ascula s uc u al abno mali ies, including inc eased
ma ix deposi ion and in imal hickening [14, 15]. Some
esul s sugges ha GPx plays a c i ical ole in egula ing
p oin lamma o y pa hways; ailing o egula e hese p oin-
lamma o y pa hways acili a es an in lamma o y and ac i-
a ed endo helium leading o endo helial dys unc ion [16].
To al an ioxidan capaci y (TAC) is he measu e o he
amoun o ee adicals sca enged by a es solu ion. I is
an analy e equen ly used o assess he an ioxidan s a us
o biological samples and can e alua e he an ioxidan
esponse agains he ee adicals p oduced in a gi en
disease [17].
A no el s udy ound a co ela ion be ween CRP con-
cen a ions wi h se e i y o pulmona y a e ial damage
and PH in dogs wi h D. immi is, inding signi ican ly in-
c eased CRP in animals wi h mild o se e e PH [18].
This ac has made i possible o belie e ha CRP could
be used o s aging and moni o ing he disease in dogs
and may wo k as an ea ly bioma ke o PH. Howe e ,
he e a e no s udies on o he APP o ma ke s o oxida-
i e s ess. The e o e, he aim o he p esen s udy was
o e alua e he ela ionship be ween PH wi h he
concen a ions o di e en posi i e (C- eac i e p o ein
[CRP] and hap oglobin [Hp]) and nega i e (albumin and
pa aoxonase-1 [PON-1]) APP, as well as he oxida i e
s ess by measu ing GPx and o al an ioxidan capaci y
(TAC) in hea wo m-in ec ed dogs a he beginning and
he end o he adul icide ea men o e alua e hei u il-
i y as diagnos ic ma ke s o PH.
Me hods
In he p esen s udy, 27 hea wo m-in ec ed dogs posi i e
o ci cula ing an igens we e included. The dogs li ed in
G an Cana ia (Spain), a hype endemic a ea o D. immi is
[19, 20]. None o he animals had ecei ed p e ious ea -
men o hea wo m in ec ion. A comple e eco d was
kep o each animal, including iden i ica ion (age, sex and
b eed), clinical his o y and demog aphic da a. The e we e
12 emales and 15 males; he mean age was 4.7 yea s
( om 3 o 9 yea s). The dogs we e di ided in o wo
g oups (<4 yea s, n=13,and>4yea s,n= 14) when he
age was e alua ed. By b eed, 13 we e mong el dogs and 14
we e pu eb eds (13 di e en b eeds). All we e posi i e o
ci cula ing D. immi is an igens using a comme cial immu-
noch oma og aphic es ki (U ano es Di o ila ia®, U ano
Ve SL, Ba celona, Spain). Dogs we e u he e alua ed o
he p esence o absence o mic o ila iae using a modi ied
Kno ’s es . In addi ion, a g oup o 10 heal hy dogs (6
males and 4 emales), wi h ages be ween 2 and 8 yea s, o
di e en b eeds we e used as con ol g oup. All hese dogs
showed no abno mali y on physical examina ion and on
ou ine hema ologic and biochemical analyses and we e
nega i e o ci cula ing D. immi is an igens.
On he day o he diagnosis (Day 0) and a he end o
he ea men (Day 120), dogs unde wen echoca dio-
g aphic examina ion using an ul asound machine wi h
The Au ho (s) Pa asi es & Vec o s 2017, 10(Suppl 2):477 Page 166 o 235
spec al and colo Dopple and mul i equency p obes
(5.5–10 MHz) (Logic P5, Gene al Elec ic, New Yo k,
USA). P esence o absence o PH was de e mined by he
Righ Pulmona y A e y Dis ensibili y Index (RPAD
Index) as p e iously desc ibed [6]. The pa asi e bu den
isible in he pulmona y a e ies and igh ca diac cham-
be s was also assessed by echoca diog aphy.
Blood was d awn om he cephalic ein o each animal
on Day 0 and Day 120 o measu e APP and ma ke s o oxi-
da i e s ess. Blood was collec ed in o ubes wi hou an i-
coagulan and se um was ob ained and ozen (−20 °C)
un il analysis. Concen a ions o CRP we e measu ed using
a human immuno u bidime ic es (CRP OSR 6147 Olym-
pus Li e and Ma e ial Science Eu ope GmbH, Lismeehan,
O’Callaghan’s Mills, Co. Cla e, I eland); Hp concen a ions
we e measu ed using a colo ime ic me hod (ki hap oglo-
bin T idel aPhase ange SAA ki , T idel a De elopmen
L d., Co. Kilda e, I eland); albumin was de e mined using a
B omoc esol g een eagen [Albumin OSR 6102 Olympus
Li e and Ma e ial Science Eu ope GmbH Lismeehan,
O’Callaghan’s Mills, Co. Cla e, I eland]; and se um PON-1
ac i i y was de e mined using p-ni ophenyl ace a e as sub-
s a e. All echniques had p e iously been alida ed o use
in dogs [21–24]. GPx and TAC we e analyzed as p e iously
desc ibed [25, 26]. All de e mina ions we e pe o med in
se um on an au oma ed biochemis y analyze (Olympus
AU600 Au oma ic Chemis y Analyze , Olympus Eu ope
GmbH, Hambu g, Ge many).
The in ec ed dogs unde wen adul icide ea men ol-
lowing he Ame ican Hea wo m Socie y ecommended
managemen p o ocol [27]. In sho , on Day 0 he dog
was diagnosed as hea wo m posi i e, s a ing wi h he
adminis a ion o doxycycline (10 mg/kg BID) o
4 weeks and he mon hly hea wo m p e en i e based
on i e mec in (6 μg/kg). On Day 60 he dog was ea ed
wi h he i s in amuscula injec ion o mela somine
(2.5 mg/kg), ollowed on Day 90 by a second injec ion
and a hi d injec ion on Day 91. On Day 120, he dog
was es ed o p esence o mic o ila iae and discha ged.
On Day 271, 6 mon hs a e comple ion, he adul icide
e icacy was con i med wi h an an igen es . Exe cise
es ic ion was ecommended un il a leas 1 mon h
a e he las mela somine injec ion.
The da a we e analyzed using he SPSS Base 22.0 so -
wa e o Windows. The nonpa ame ical Mann-Whi ney
U es was used o compa e esul s ob ained o dogs
nega i e and posi i e o hea wo m disease and also o
he compa ison be ween diseased dogs wi h PH and
wi hou PH. K uskal-Wallis wi h Dunn’s mul iple com-
pa ison es was used o he compa ison be ween dogs
g ouped by PH s a us. Wilcoxon signed ank es was
used o compa e he esul s ob ained o he di e en
analy es a wo di e en imes (Day 0 and Day 120). In
all cases, a P alue <0.05 was de e mined as signi ican .
All o he owne s ga e hei consen o pa icipa e in
his s udy. The s udy was app o ed by he e hical com-
mi ee o he Ve e ina y Medicine Se ice o he Uni e -
si y o Las Palmas de G an Cana ia and was ca ied ou
in acco dance wi h he cu en Eu opean legisla ion on
animal p o ec ion.
Resul s
Absence o p esence o PH, as well as PH se e i y, was
based on he de e mina ion o he RPAD Index. An
Index be ween 35 and 28% was co ela ed wi h mild PH
(30–55 mmHg), be ween 27 and 23% wi h mode a e PH
(56–79 mmHg), and 22% o less wi h se e e PH
(>79 mmHg). On Day 0, 62.9% (17/27) o he dogs
showed PH (25.9% mild, 37% mode a e-se e e PH). Al-
hough he RPAD Indexes we e lowe in dogs <4 yea s
compa ed wi h olde dogs (>4 yea s), he di e ences
we e no signi ican .
No wo ms we e isualized by echoca diog aphy in any
o he s udied dogs a he end o he ea men (Day
120) and 59.2% (16/27) p esen ed PH (37 mild, 22.2%
mode a e-se e e PH). PH was s ill p esen in 70.6% (12/
17) o he dogs wi h PH a he beginning o he
ea men , and 40% (4/10) o he dogs wi h no mal
pulmona y p essu e a he beginning o he ea men
showed PH on Day 120.
A he beginning o he s udy, he concen a ions o
CRP in he in ec ed dogs (mean: 23.4 mg/L) we e signi i-
can ly highe compa ed wi h hose ob ained in he
con ol g oup (mean: 6.45; SD: 2.36; P< 0.05). By age,
CRP was signi ican ly highe in olde dogs (mean:
32.1 mg/L e sus 13.9 mg/L; P< 0.005). CRP concen a-
ions we e highe in dogs wi h PH (mean: 30.2 mg/L)
when compa ing wi h dogs ha had no mal pulmona y
p essu e (mean: 12.03 mg/L; P< 0.005). CRP concen a-
ions we e highe in dogs wi h mode a e-se e e PH
(mean: 39.6 mg/L) when compa ed wi h dogs ha had
mild PH (mean: 16.8 mg/L; P< 0.005) (Fig. 1).
On Day 120, CRP concen a ions dec eased in all
animals (mean: 7.7 mg/L) as compa ed wi h Day 0
(P< 0.005). By age, means we e 8.6 mg/L (<4 yea s) and
7.2 mg/L (>4 yea s), wi h no signi ican di e ences. By PH
s a us, he esul s showed ha CRP alues we e lowe in
dogs wi hou PH ( eaching a mean concen a ion o
5.6 mg/L) han in dogs wi h PH (mean: 9 mg/L; P<0.05).
By se e i y, he dogs wi h mild PH (mean: 6.5 mg/L)
showed lowe CRP alues han hose wi h mode a e-
se e e PH (mean: 14 mg/L; P< 0.05) (see Fig. 1).
Concen a ions o Hp we e signi ican ly dec eased in
dogs wi h hea wo m on Day 0 (mean: 1.38 g/L) when
compa ed wi h alues ob ained in he con ol g oup
(mean: 2.16; SD: 0.86; P< 0.05). When age was e alu-
a ed, olde dogs showed highe le els (mean: 1.9 g/L e -
sus mean: 0.85 g/L), wi h no signi ican di e ences.
The Au ho (s) Pa asi es & Vec o s 2017, 10(Suppl 2):477 Page 167 o 235
When he RPAD Index was e alua ed, concen a ions we e
highe in dogs wi h PH (mean: 1.39 g/L) compa ed wi h
dogs wi h no mal pulmona y p essu e (mean: 1.05 g/L), al-
hough he di e ences we e no s a is ically signi ican . By
se e i y, Hp concen a ions we e highe in dogs wi h
mode a e-se e e PH (mean: 1.85 g/L) han in dogs wi h
mild PH (mean: 0.86 g/L; P<0.005)(seeFig.1).
On Day 120, Hp concen a ions inc eased in all animals
(mean: 3.26 g/L; P< 0.05). Hp concen a ion was highe
in olde dogs (mean: 3.4 g/L e sus mean: 2.9 g/L), wi h
no signi ican di e ences; and i was highe in dogs wi h
PH (mean: 3.68 g/L; P< 0.005). In addi ion, dogs wi h
mode a e-se e e PH showed highe alues a he end o
he ea men han hose wi h mild PH (mean: 5.03 g/L
e sus mean: 3.01 g/L; P<0.005)(seeFig.1).
When nega i e APP we e e alua ed, i was ound ha
concen a ions on Day 0 we e signi ican ly diminished in
dogs wi h hea wo m (means: 2.8 g/dL, P< 0.005 o al-
bumin and 2.24 IU/mL, P< 0.05 o PON-1) wi h ega d
o hose ob ained in dogs o he con ol g oup (mean
3.32, SD: 0.31 o albumin and mean: 2.79, SD: 0.55 o
PON-1). Concen a ions we e lowe in dogs wi h PH
(means: 2.6 g/dL o albumin and 2.13 IU/mL o PON-
1) when compa ed wi h dogs wi hou PH (means: 3.1 o
albumin g/dL and 2.45 IU/mL o PON-1) (P< 0.05 o
albumin). When he se e i y o he PH was assessed, i
was obse ed ha nega i e APP concen a ions we e
lowe in dogs wi h mode a e-se e e PH (means: 2.5 g/
dL o albumin and 1.98 IU/mL o PON-1) han in dogs
wi h mild PH (means: 2.7 g/dL o albumin and 2.25 IU/
mL o PON-1), he di e ences no being s a is ically
signi ican (Fig. 2). No signi ican di e ences we e ob-
se ed be ween g oups o age in nega i e APP.
On Day 120, albumin and PON-1 showed a signi ican
inc ease when compa ed wi h Day 0 (P< 0.05 o albu-
min and PON-1). Howe e , no signi ican di e ences
we e obse ed be ween g oups wi h ega d o he age o
he p esence o absence o PH.
Rega ding he bioma ke s o oxida i e s ess, GPx and
TAC, he e a e no s a is ically signi ican di e ences in
he se um alues be ween dogs wi h and wi hou hea -
wo m disease. In addi ion, no signi ican changes we e
ound be ween dogs be o e and a e ea men and wi h
and wi hou hype ension.
Discussion
The changes ound in he g oup o hea wo m-in ec ed
dogs o he posi i e (CRP and Hp) and nega i e APP
(albumin and PON-1) on Day 0 compa ed wi h he
heal hy dogs p obably e lec he in lamma o y p ocess
associa ed wi h he disease, as p e iously desc ibed [12].
Fu he mo e, mean alues o all analy es excep Hp a e
Fig. 1 Se um concen a ions o posi i e acu e phase p o eins CRP on Day 0 (a)andDay120(b), and Hp on Day 0 (c)andDay120(d), in dogs wi h
hea wo m wi hou pulmona y hype ension (no HP) (RPAD Index ≥36%), wi h mild pulmona y hype ension (mild HP) (RPAD Index 28–35%) and
mode a e o se e e pulmona y hype ension (Mod-se HP) (RPAD Index ≤27%). The box plo s ep esen median (solid ho izon al lines wi hin boxes),
25 h and 75 h pe cen iles (boxes) and minimum and maximum alues (whiske s). (*): signi ican di e ences be ween g oups. NS: no signi ican
The Au ho (s) Pa asi es & Vec o s 2017, 10(Suppl 2):477 Page 168 o 235
ea men we e below he uppe limi o he e e ence
ange o ou labo a o y, which is 12 mg/L in he case o
CRP, 3 g/L o Hp, 36 g/L o albumin and 4.3 IU/mL
o PON-1. The e o e he s udy demons a ed
no maliza ion in mos o he concen a ions o he s ud-
ied APP a e he elimina ion o he pa asi es, simila o
o he esea ch [12, 13], while he inc eases obse ed in
Hp on Day 120 a e simila o a p e ious s udy [13].
When he APP we e assessed acco ding o he PH s a-
us, i was obse ed ha dogs wi h PH a he beginning
o he ea men showed highe CRP concen a ions; u -
he mo e, hese CRP concen a ions inc eased wi h he
se e i y, he highes being ound in dogs wi h mode a e-
se e e PH. Venco e al. [18] desc ibed simila indings,
epo ing ha dogs wi h mild o se e e PH p esen ed
signi ican ly inc eased CRP. The beha io o he Hp was
simila ; Hp inc eased in dogs wi h PH, he g ea e in-
c ease being in hose wi h mode a e-se e e PH.
PH is a ch onic condi ion caused by he p esence o
hea wo ms, mainly h ough he de elopmen o p oli -
e a i e enda e i is and ib osis a he capilla y beds,
among o he ac o s [1, 2, 28]. I is possible ha CRP
play an impo an ole in he ch onic p ocess o emod-
eling o he ascula u e and i s concen a ions co ela e
wi h he se e i y and ch onici y o he disease [10, 18].
S udies ha e been published ha show ha CRP is able
o enhance smoo h muscle p oli e a ion and sec e ion o
endo helin-1, a po en asocons ic o in humans [29],
and mild CRP ele a ions ha e been epo ed om clinic-
ally ea ly s ages o hea wo m in ec ion [30]. Because
PH is a equen and se ious complica ion in hea wo m
disease, i s objec i e de e mina ion is impo an . The de-
ec ion o inc eased concen a ions o CRP and Hp may
be used o de e mine a high le el o suspicion o pul-
mona y hype ension in he animals a ec ed, so hese
APP may be use ul as ea ly bioma ke s o PH and o
s age he disease.
A e he adul icide ea men , CRP was lowe in he
absence o PH compa ed wi h dogs wi h pe sis en PH,
especially in hose wi h mode a e-se e e PH. Rega ding
Hp, concen a ions we e highe in dogs wi h mode a e-
se e e PH. A he end o he ea men , 70.6% o he
dogs wi h PH on Day 0 s ill p esen ed his pa hological
al e a ion, which indica es he pe sis ence o he ascula
damage 1 mon h a e he end o he adul icide ea -
men and when he pa asi es a e mos likely o be dead.
Fu he mo e, 40% o he dogs wi hou PH de eloped PH
du ing he ea men . This may be caused by ei he em-
bolism o dead hea wo ms, which can cause acu e clin-
ical signs o PH, o by p oli e a i e in imal changes,
which lead o s uc u al damage o he ascula u e and
sus ained PH [31, 32]. Howe e , less se e e a e ial
Fig. 2 Se um concen a ions o nega i e acu e phase p o eins albumin on Day 0 (a) and Day 120 (b), and PON-1 on Day 0 (c) and Day 120 (d) in dogs
wi h hea wo m wi hou pulmona y hype ension (no HP) (RPAD Index ≥36%), wi h mild pulmona y hype ension (mild HP) (RPAD Index 28–35%) and
mode a e o se e e pulmona y hype ension (Mod-se HP) (RPAD Index ≤27%). The box plo s ep esen median (solid e ical lines wi hin boxes), 25 h
and 75 h pe cen iles (boxes) and minimum and maximum alues (whiske s). (*): signi ican di e ences be ween g oups. NS: no signi ican
The Au ho (s) Pa asi es & Vec o s 2017, 10(Suppl 2):477 Page 169 o 235

lesions and i ual absence o emboli in he cu en ly ec-
ommended adul icide p o ocol a e obse ed [30], and u -
he esea ch should be done o assess he deg ee o
e e sibili y o ascula damage in dogs unde his p o ocol.
Al hough i is no possible o de e mine he du a ion
o he in ec ion –and, he e o e, he ch onici y –in he
na u ally in ec ed dogs om his s udy, conside a ion
mus be gi en o his ac . I could be said ha olde
dogs a e mo e commonly a ec ed by ch onic in ec ions.
The CRP was signi ican ly highe in olde dogs on Day
0, which could e lec he ch onici y o he in ec ion.
The he e ogenei y o animals makes i impossible o dis-
cuss he possible in luence o he b eed in he esul s.
These da a highligh he need o keep moni o ing he
dogs a e inishing he adul icide ea men and assess
he e olu ion o PH. Fo his, CRP and Hp could be use-
ul o moni o he e olu ion o he pa ien and indi ec ly
e alua e he pe sis ence o a e ial damage once he pa -
asi es ha e been elimina ed. Also, inc eases o CRP a e
he ea men migh spa k a suspicion o de elopmen o
PH o wo sening in hese pa ien s.
The nega i e APP (albumin and PON-1) beha ed simi-
la ly o p e ious s udies and dec eased in dogs wi h
hea wo m [12]. Also, hey showed an associa ion be-
ween p esence and absence o PH as well as se e i y o
PH, since he dogs wi h mode a e-se e e PH showed
lowe alues. Howe e , his associa ion was no s a is i-
cally signi ican , and u he esea ch mus be ca ied
ou o assess hei clinical u ili y.
No di e ences we e ound in he ma ke s o oxida i e
s ess be ween hea wo m-posi i e and con ol g oups,
which may indica e ha no impo an phenomena o
oxida i e damage we e occu ing in hea wo m-in ec ed
dogs o maybe ha he assays used o oxida i e damage
e alua ion we e no sensi i e enough o de ec changes
in his disease. P e ious s udies showed a ela ionship
be ween de iciency in ma ke s o oxida i e s ess and
endo helial dys unc ion [14–16]. Endo helial dys unc ion
is a pa hological condi ion mainly de ined by an imbal-
ance be ween subs ances and is cha ac e ized by p oin-
lamma o y, asocons ic ing, p o h ombo ic and
p oli e a i e s a es [33, 34]. As p oli e a i e enda e i is
is ep esen ed by hese al e a ions, a ela ionship be-
ween he ma ke s o oxida i e s ess GPx and TAC was
sough . As his is he i s esea ch o e alua e he
ma ke s o oxida i e s ess in hea wo m disease, u he
s udies i possible using o he bioma ke s o he assess-
men o s ess esponses a e ecommended.
Conclusions
The esul s showed ha posi i e APP, CRP and Hp in-
c ease in dogs wi h PH. Al hough u he esea ch is ne-
cessa y, CRP and Hp ha e a po en ial p ognos ic ole in
dogs wi h di o ila iasis as inc eases in posi i e APP
co ela ed wi h p esence and se e i y o PH. Mo eo e ,
high concen a ions o hese APP pe sis ed in dogs wi h
PH 1 mon h a e he end o he adul icide ea men ,
while in he case o CRP hey e u ned o no mal in
dogs in he absence o PH; he e o e, CRP could indi -
ec ly e alua e he pe sis ence o a e ial damage once
he pa asi es ha e been elimina ed.
The nega i e APP also showed a po en ial alue as
ma ke s o PH, al hough u he esea ch is necessa y o
de e mine he u ili y.
Abb e ia ions
APP: Acu e phase p o eins; CRP: C- eac i e p o ein; GPx: Glu a hione
pe oxidase; Hp: Hap oglobin; PH: Pulmona y hype ension; PON-
1: Pa aoxonase-1; RPAD Index: Righ pulmona y a e y dis ensibili y index;
TAC: To al an ioxidan capaci y
Funding
Financial suppo was p o ided by he p og amme “P og ama Pos doc o al
pa a la. Especialización de Pe sonal In es igado de la ULPGC,”Spain,
h ough a pos doc o al g an . The a icle publica ion ee was unded by he
Ame ican Hea wo m Socie y.
A ailabili y o da a and ma e ials
All da a gene a ed o analyzed du ing his s udy a e included in his
published a icle.
Abou his supplemen
This a icle has been published as pa o Pa asi es and Vec o s Volume 10
Supplemen 2, 2017: P oceedings o he 15 h Ame ican Hea wo m Socie y
T iennial Symposium 2016. The ull con en s o he supplemen a e a ailable
online a h ps://pa asi esand ec o s.biomedcen al.com/a icles/
supplemen s/ olume-10-supplemen -2.
Au ho s’con ibu ions
EC, JJC, ACV and JAMA designed he s udy, o ganized he ieldwo k,
analyzed he ssda a and w o e he manusc ip . SMS and AT p ocessed and
analyzed he samples. All au ho s ead and app o ed he inal manusc ip .
E hics app o al and consen o pa icipa e
All o he owne s ga e hei consen o pa icipa e in his s udy. The s udy
was app o ed by he e hical commi ee o he Ve e ina y Medicine Se ice
o he Uni e si y o Las Palmas de G an Cana ia and was ca ied ou in
acco dance wi h he cu en Eu opean legisla ion on animal p o ec ion.
Consen o publica ion
No applicable
Compe ing in e es s
The au ho s decla e ha hey ha e no compe ing in e es s.
Publishe ’sNo e
Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in
published maps and ins i u ional a ilia ions.
Au ho de ails
1
Facul y o Ve e ina y Medicine, Resea ch Ins i u e o Biomedical and Heal h
Sciences (IUIBS), Uni e si y o Las Palmas de G an Cana ia, T asmon aña s/n,
35413-A ucas, Las Palmas, G an Cana ia, Spain.
2
In e disciplina y Labo a o y o
Clinical Analysis (In e lab-UMU), Ve e ina y School, Uni e si y o Mu cia,
Mu cia, Spain.
3
Medicina y Ci ugía Animal, Facul y o Ve e ina y Medicine,
Uni e si y Complu ense o Mad id, Mad id, Spain.
Published: 9 No embe 2017
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