Prekondicioniranje izolovanog srca ishemijom i inhibitorima protonske pumpe: efekti na kardiodinamiku i koronarni protok
Preconditioning of isolated rat heart with ischemia and proton pump inhibitors: Effects on cardiodinamic and coronary flow
Докторанд
Jeremić, NevenaМентор
Jakovljević, VladimirЧланови комисије
Novokmet, SlobodanĐurić, Dragan
Folić, Marko
Метаподаци
Приказ свих података о дисертацијиСажетак
Cilj ove studije je bio da ispita
efekate prekondicioniranja ishemijom i
efekte akutne administracije različitih
lekova iz grupe inhibitora protonske
pumpe kao farmakoloških agenasa u modelu
prekondicioniranja na funkcionisanje
miokarda i koronarnu cirkulaciju
izolovanog srca pacova kao i moguću ulogu
oksidacionog stresa.
Metode. U studiji je analizirano 60 pacova
(Vistar albino soj, muški pol, starosti 8
nedelja, telesne mase 250±50g) kojima se
izolovalo srce i perfundovalo metodom
retrogradne perfuzije po Langendorfu
(Langendorff apparatus, Experimetria Ltd,
1062 Budapest, Hungary) pri konstantnom
koronarnom perfuzionom pritisku od 70
sm H2O. Istraživanje je bilo podeljeno u
pet (5) eksperimentalnih grupa. Vrednost
koronarnog protoka su određivane
floumetrijski. U levoj komori su
kontinuirano praćeni parametri funkcije
leve komore: a) dp/dt max - maksimalna
stopa promene pritiska u levoj komori, b)
dp/dt min - minimalna stopa promene
pritiska u levoj komori, ...v) SLVP -
sistolni pritisak leve komore, g) DLVP -
dijastolni pritisak leve komore i đ) HR -
srčana frekvenca. U uzorcima koronarnog
venskog efluenta spektrofotometrijskim
metodama su određivani sledeći markeri
oksidacionog stresa: indeks lipidne
peroksidacije – meren kao TBARS, azot
monoksid u formi nitrita (NO2),
superoksid anjon radikal (O2
-), i vodonik peroksid (H2O2).
Rezultati. Rezultati istraživanja su
prikazani na 10 tabela i 50 grafikona.
Sumarno posmatrano, ishemijsko
prekondicioniranje je najpozitivniji
efekat ostvarilo u očuvanju perfuzije
miokarda i srčane frekvence, dok je
prekondicioniranje farmakološkim
agensima (lekovima iz grupe inhibitora
protonske pumpe) pokazalo bolje rezultate
u očuvanju oba parametra kontraktilnosti.
Kardiodinamski efekti svih ispitivanih
lekova iz grupe IPP nisu bili
posredovani oksidacionim stresom.
Zaključak. Obe vrste prekondicioniranja
su pokazale pozitivan efekat na
funkcionalni oporavak miokarda, s tim
što je taj uticaj u slučaju farmakološkog
prekondicioniranja bio dominanatan na
očuvanje kontraktilne sile, dok je u slučaju
ishemijskog prekondicioniranja efekat
bio fokusiran na očuvanje koronarne
reaktivnosti srca. Prilikom međusobnog
poređenja ostvarenih efekata ispitivanih
IPP, možemo zaključiti da se
najznačajniji pozitivni efekat na oporavak
miokarda sreće u slučaju omeprazola i
pantoprazola.
The aim of this study was to
investigate the effect of applying
preconditioning ischemia and effects of acute
administration of different drugs from the
group of proton pump inhibitors as
pharmacological agents in the model of
preconditioning on myocardial function and
coronary circulation in isolated rat heart as
well as the possible role of oxidative stress.
Methods. Sixty rats (Wistar, albino, males,
aged 8 weeks, body weight 250±50 g) had the
hearts isolated and perfused by using
retrograde perfusion method according to
Lagendorff (Langendorff apparatus,
Experimetria Ltd, 1062 Budapest, Hungary) at
constant coronary perfusion pressure of 70 cm
H2О. The research included five (5)
experimental groups. The values of coronary
flow were determined fluorometrically. The
next parameters of left ventricle function were
continuously followed: a) dp/dt max –
maximum rate of pressure change in the left
ventricle, b) dp/dt min - minimum rate of
pressure change in the lef...t ventricle c) SLVP –
systole left ventricle pressure, d) DLVP -
diastole left ventricle pressure and e) HR –
heart rate. In the samples of coronary venous
effluent the following parameters were
determined using spectrophotometric methods:
lipid peroxidation index – measured as
TBARS, nitrogen monoxide in the form of
nitrite (NO2), superoxide anion radical (O2
-),
and hydrogen peroxide (H2О2).
Results. The research results are presented in
10 tables and 50 graphs. In summary, ischemic
preconditioning is the most positive effect
achieved in the preservation of myocardial
perfusion and heart rate, while the
preconditioning pharmacological agents (drugs
from the group of proton pump inhibitors)
showed better results in terms of both
parameters contractility. Effects on
cardiodynamic of all the tested drugs from the
group of PPIs were not mediated by oxidative
stress.
Conclusion. Both types of preconditioning
showed positive effect on functional recovery
of the myocardium, with the impact in the
event of pharmacological preconditioning that
was most dominant on the preservation of
contractile force, while in the case of ischemic
preconditioning effect was focused on
preservation of coronary heart reactivity. When
mutual comparison of actual effects of tested
IPP, we can conclude that the most important
positive effect on the recovery of myocardial
we noted in the case of omeprazole and
pantoprazole.