The expe ience o he applica ion o asco binic acid as an ioxidan a e co ona y a e y su ge y
wi h use o ca diopulmona y bypass [in Russian].
Reb o a TY, Shipulin VM, A anase SA, Vo obe a EV, Kiiko OG.
Ka diologiia. 2012;52(7):73-6.
PubMed eco d
h p s ://www.ncbi.nlm.nih.go /pubmed/22839718
English ansla ion o his pape was a anged by Ha i Hemilä in 2015
[email p o ec ed]
h ps://www.m .helsinki. i/home/hemila
This ial was included in a me a-analysis on i amin C and a ial ib illa ion by Ha i Hemilä:
h ps://doi.o g/10.1186/s12872-017-0478-5
h p://www.ncbi.nlm.nih.go /pmc/a icles/pmc5286679
The Russian pape :
Опыт применения аскорбиновой кислоты как антиоксиданта у пациентов после операции
коронарного шунтирования с использованием искусственного кровообращения
Реброва Т.Ю., Шипулин В.М., Афанасьев С.А., Воробьева Е.В., Кийко О.Г.
h p s ://www.med es nik. u/lib a y/a icle/2904
1
The expe ience o he applica ion o asco binic acid as an ioxidan a e co ona y a e y su ge y
wi h use o ca diopulmona y bypass
Reb o a TY, Shipulin VM, A anase SA, Vo obe a EV, Kiiko OG.
Ins i u e o Ca diology, Sibe ian B anch, Russian Academy o Medical Sciences, 634012 Tomsk,
Kiye skaya s ., 111a.
Keywo ds: a ial ib illa ion, ao oco ona y bypass, lipid pe oxida ion.
One o he mos common complica ions ha occu a e su gical ea men o
co ona y insu iciency in pa ien s wi h ischemic hea disease (IHD) is a hy hmia [1, 2].
Also ele an in his ega d is he inding by L.A. Boke ia ha di ec myoca dial
e ascula iza ion can cu e a hy hmia only in a e y small numbe o pa ien s [3]. The
p ima y peak o ca diac a hy hmia occu s du ing he i s h ee days a e ope a ion [4],
hen a sinus hy hm is e-es ablished. Acco ding o he li e a u e da a, pa ien s wi h pos -
ope a i e a hy hmia, in pa icula hose wi h a ial ib illa ion, ha e signi ican ly lowe
30-day and six-mon h su i al a es han hose wi hou complica ions [5].
An ia hy hmics, such as β-ad enoblocke s, a e ecommended o p e en such
complica ions. Howe e , hey a e no always e ec i e, because almos all
an ia hy hmic agen s a e capable o p oa hy hmic e ec [6, 7].
The high equency o a hy hmia in he pos -ope a i e pe iod may e lec
me abolic diso de s ha a e occu ing in ca diac muscle cells [4]. I has been es ablished
expe imen ally ha one o he mechanisms o ca diac muscle damage as a esul o
ischemic and epe usion s ess is uncon olled lipid pe oxida ion (LPO), which damages
he s uc u e and unc ion o cell memb anes [8, 9].
The aim o his s udy was o in es iga e he ole o oxidan s ess in he
de elopmen o a hy hmia in he ea ly pos -ope a i e pe iod a e co ona y a e y
bypass su ge y, as well as he possibili y o p e en ing such a hy hmia wi h asco bic
acid.
2
Ma e ials and me hods
The s udy was conduc ed wi h 40 (male) pa ien s su e ing om ch onic IHD, who
we e admi ed o he Resea ch Ins i u e o Ca diology o he Sibe ian b anch o he Russian
Academy o Medical Sciences. All pa ien s we e ecommended su gical ea men . Pa ien s
aking pa in he s udy we e di ided in o wo compa able g oups: he main g oup and he
con ol g oup. A b ie clinical p o ile o he obse ed pa ien g oups is p o ided in Table 1.
All he pa ien s ecei ed s anda d basic ea men be o e and a e ope a ion, including β-
ad enoblocke s (me op olol, bisop olol, a enolol). Fo pa ien s in he main g oup, basic
ea men was supplemen ed wi h asco bic acid. The asco bic acid was adminis e ed as 1 g
wa e -soluble able s as ollows: 2 g he e ening be o e he ope a ion and 1 g wice pe day
o he 5 days a e he ope a ion.
A hy hmia was obse ed in pa ien s du ing he p e- and pos -ope a i e pe iod by
ECG moni o ing wi h a Siemens SC 9000 moni o .
Be o e adminis e ing asco bic acid, as well as on he 1s and 5 h days a e su ge y,
enous blood samples we e aken om all pa ien s. Plasma aken om hese samples was
ozen and s o ed a he empe a u e o liquid ni ogen. The biosamples we e used o
e alua e he in ensi y o oxida i e s ess, which was assessed on he basis o he
concen a ion o conjuga ed dienes (CD) [10] and he ac i i y o he an ioxidan enzyme
ca alase [11].
A compa ison o he da a was conduc ed using he Mann-Whi ney U es
and χ2. The di e ences we e conside ed s a is ically signi ican when p<0.05.
3
Table 1. Clinical p o ile o he obse ed g oups o pa ien s
Pa ame e Con ol g oup Main g oup p
Numbe o pa ien s 20 20
Male, % 100 100
Mean age, yea s 61±6.6 56.4±6.7 0.68
Angina FC II, % 21 19 0.88
Angina FC III, % 79 81 0.88
Uns able angina, % 17 11 0.49
CHF FC II (NYHA classi ica ion), % 78 75 0.78
CHF FC III (NYHA classi ica ion), % 22 25 0.78
Pos in a c ion ca dioscle osis, % 61 57 0.79
Hype choles e olemia, % 78 75 0.78
Class I-II obesi y,% 30 32 0.89
Class II-III a e ial hype ension, % 83 89 0.49
Diabe es, % 17 28 0.35
Smoking, % 39 53 0.31
Associa ed a e iopa hies (s enoses >50%), % 43 46 0.83
Du a ion o CPB, min 104.7±27.9 107.3±39.9 0.67
Du a ion o ischemia, min 68.6±24.3 72.2±26.2 0.65
Numbe o bypasses 3.0±1.2 3.2±1.0 0.59
No e. FC — unc ional class; CHF — ch onic hea ailu e; NYHA — New Yo k Hea Associa ion
classi ica ion; CPB — ca diopulmona y bypass.
4
Resul s and discussion
The esul s o CD concen a ion and ca alase ac i i y in he blood plasma o he obse ed pa ien
g oups a e shown in Table 2. The da a shows ha he e we e no signi ican di e ences in he ini ial
pa ame e s be ween he g oups. This is en i ely consis en wi h he da a shown in Table 1 and he ac
ha IHD de elopmen is accompanied by he ac i a ion o LPO in he ca diac muscle and blood o
pa ien s [12]. Howe e , in he pos -ope a i e pe iod, CD concen a ion and ca alase ac i i y we e
di e en be ween he obse ed pa ien g oups. Fo example, he CD concen a ion in he blood plasma
o he con ol g oup pa ien s had no changed o a s a is ically signi ican ex en 24 hou s and 5 days
a e su ge y. In pa ien s aking asco bic acid, a s a is ically signi ican dec ease in CD concen a ion
om he ini ial alues o he g oup was obse ed 24 hou s a e he ope a ion. Gi en ha CDs a e
p ima y p oduc s o LPO [13], he dec ease in concen a ion may be in e p e ed as an indica ion ha
asco bic acid blocks he de elopmen o oxidan s ess du ing i s ini ial s ages. Unde no mal
condi ions, he LPO p ocess is cons an ly con olled by he body's an ioxidan sys em. Unde he
condi ions o ch onic IHD wi h epea ed episodes o ischemia and epe usion, exhaus ion o some
an ioxidan s occu s [8], which can nega i ely impac he e ec i eness o LPO supp ession unde acu e
ischemic s ess. Indeed, as shown abo e, pa ien s su e ing om IHD wi h se e e hea ailu e ha e a
signi ican ly lowe le el o endogenous lipid-soluble an ioxidan s [14].
In o de o e alua e he s a us o he an ioxidan sys em in pa ien s o he obse ed g oups and he
esponsi eness o he sys em du ing ea men wi h asco bic acid, we assessed he ac i i y o ca alase,
he majo enzyme o an ioxidan p o ec ion.
As shown in Table 2, he e we e no s a is ically signi ican di e ences in ca alase ac i i y in
he p e-ope a i e pe iod be ween pa ien s in he obse ed g oups. Howe e , 24 hou s a e su ge y we
iden i ied a s a is ically signi ican inc ease (g ea e han 2.1) in he ac i i y o his enzyme in he
pa ien s o he con ol g oup. On he 5 h day, ca alase ac i i y had allen, bu s ill emained highe han
be o e he su ge y.This pa e n o ac i i y in one o he majo an ioxidan enzymes can be in e p e ed as
an indica o o he compensa o y e o o he an ioxidan sys em in esponse o ischemic and
epe usion s ess, o which he ca diac muscle has been exposed du ing su gical in e en ion. A he
same ime, an inc ease in ca alase ac i i y sugges s ha he endogenous an ioxidan sys em o pa ien s
in he s udy g oup, o a leas i s enzyme componen , main ains a unc ional ese e.
We did no no ice any signi ican changes in ca alase ac i i y in pa ien s o he main g oup du ing
he en i e pe iod o he s udy. The pa e n o ca alase enzyme ac i i y in his g oup may be he esul o
an ioxidan s abili y in he body as a esul o aking asco bic acid.
5
A p esen , he pa hogenesis o epe usion a hy hmias, including hose occu ing a e su gical
ea men o IHD wi h he use o ca diopulmona y bypass, is belie ed o be ela ed o he “oxygen
pa adox” and consequen ly o he pa hological ac i a ion o LPO p ocesses [1, 2, 4].
The p esen ed da a sugges s ha asco bic acid does signi ican ly educe LPO ac i a ion in he
case o ischemic and epe usion s ess on ca diac muscle, al hough i does no ully p e en ac i a ion.
In hese ci cums ances, we igh ly expec less p onounced a hy hmia associa ed wi h hea ailu e.
Indeed, acco ding o ou da a, eco e y o he co ona y low in he con ol g oup in 20% o cases
(4 pa ien s) was accompanied by he de elopmen o a ial ib illa ion in he pos -ope a i e pe iod. In
he g oup o pa ien s ecei ing asco bic acid, he occu ence a e o a ial ib illa ion was signi ican ly
lowe (χ2=4.11; р=0.04) and was obse ed only in 5% o cases (one pa ien ). Such a clea all in
a hy hmia a e in pa ien s o he main g oup indica es ha he elec ic s abili y o he hea muscle
inc eased in he pos -ope a i e pe iod.
I appea s ha a dec ease in he in ensi y o ee- adical p ocesses as a esul o aking asco bic
acid has a posi i e e ec on he s uc u e and unc ion o ca diac cell memb anes. The e o e, acco ding
o cu en unde s anding, he ca dio-p o ec i e e ec o an ioxidan s is ela ed o p ese a ion o he
chemical composi ion o he lipid bilaye and he unc ioning o he ionic channels o cell memb anes
[15].
6
Table 2. Pa ame e s o ca alase ac i i y and conjuga ed diene concen a ion in blood plasma o
ca diac su ge y pa ien s
Phase o s udy Con ol g oup (n=20) Main g oup (n=20) p
Ca alase
P e-ope a i e (1) 16.7±6.8
p1-2=0.009
17.7±9.1
p1-2=0.78 0.24
24 hou s a e ope a ion (2) 36.1±6.7
p2-3=0.003
23.8±6.4
p2-3=0.31 0.02
5 days a e ope a ion (3) 25.8±5.6
p3-1=0.53
18.0±4.1
p3-1=0.39 0.36
Conjuga ed dienes
P e-ope a i e (1) 2.7 ±0.87
p1-2=0.041
2.96 ±1.09
p1-2=0.0007 0.49
24 hou s a e ope a ion (2) 2.16±0.58
p2-3=0.87
1.77 ±0.97
p2-3=0.13 0.08
5 days a e ope a ion (3) 2.15±0.59
p3-1=0.41
2.2±1.31
p3-1=0.001 0.51
No e. р1-2 — signi icance o di e ences be ween he pa ame e s in he g oup be o e ope a ion
and 24 hou s a e ope a ion;
р2-3 — signi icance o di e ences be ween he pa ame e s in he g oup 24 hou s
and on he 5 h day a e ope a ion;
р3-1 — signi icance o di e ences be ween he pa ame e s in he g oup be o e ope a ion
and on he 5 h day a e ope a ion.
Conclusion
The esul s o he s udy show ha p esc ibing asco bic acid can e ec i ely supp ess he de elopmen
o oxidan s ess o su gical ea men o ischemic hea disease using a ca diopulmona y bypass
machine. Howe e , u he clinical and labo a o y in es iga ions mus be conduc ed o de e mine
whe he including asco bic acid in he medica ion o his kind o pa ien o p e en a hy hmia in he
pos -ope a i e pe iod is app op ia e.
Re e ences, see he Russian e sion:
h p s ://www.med es nik. u/lib a y/a icle/2904
7
