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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 6, November/December 2017
AFRICA
389
The effect of iloprost and sildenafil, alone and in
combination, on myocardial ischaemia and nitric oxide
and irisin levels
Suna Aydin, Tuncay Kuloglu, Suleyman Aydin, Meltem Yardim, Davut Azboy, Zeki Temizturk, Ali Kemal
Kalkan, Mehmet Nesimi Eren
Abstract
Aim:
Insufficient oxygen supply to organs and tissues due to
reduced arterial or venous blood flow results in ischaemia,
during which, although ATP production stops, AMP and
adenosine continue to be produced from ATP. The fate of
irisin, which causes the production of heat instead of ATP
during ischaemia, is unknown. Iloprost and sildenafil are
two pharmaceutical agents that mediate the resumption of
reperfusion (blood supply) via vasodilatation during ischae-
mic conditions. Our study aimed to explore the effects of
iloprost and sildenafil on irisin levels in the heart, liver and
kidney tissues and whether these pharmaceutical agents had
any impact on serum irisin and nitric oxide levels in rats with
induced experimental myocardial ischaemia.
Methods:
The study included adult male Sprague-Dawley rats
aged 10 months and weighing between 250 and 280 g. The
animals were randomly allocated to eight groups, with five rats
in each group. The groups were: sham (control), iloprost (ILO),
sildenafil (SIL), ILO
+
SIL, myocardial ischaemia (MI), MI
+
ILO, MI
+
SIL and MI
+
ILO
+
SIL. The treatment protocols
were implemented before inducing ischaemia, which was done
by occluding the left coronary artery with a plastic ligature for
30 minutes. Following the reperfusion procedure, all rats were
sacrificed after 24 hours, and their heart, liver and kidney
tissues and blood samples were collected for analyses. An
immunohistochemical method was used to measure the change
in irisin levels, the ELISA method to quantify blood irisin
levels, and Griess’ assay to determine nitric oxide (NO) levels
in the serum and tissue. Myocardial ischaemia was confirmed
based on the results of Masson’s trichrome staining, as well as
levels of troponin and creatine kinase MB.
Results:
Irisin levels in biological tissue and serum dropped
statistically significantly in the ischaemic group (MI), but
were restored with ILO and SIL administration. Individual
SIL administration was more potently restorative than indi-
vidual ILO administration or the combined administration
of the two agents. NO level, on the other hand, showed the
opposite tendency, reaching the highest level in the MI group,
and falling with the use of pharmaceutical agents.
Conclusions:
Individual or combined administration of ILO
and SIL reduced myocardial ischaemia and NO levels, and
increased irisin levels. Elevated levels of irisin obtained by
drug administration could possibly contribute to accelerated
wound recovery by local heat production. Sildenafil was more
effective than iloprost in eliminating ischaemia and may be the
first choice in offsetting the effects of ischaemia in the future.
Keywords:
iloprost, sildenafil, nitric oxide, irisin, myocardial
ischaemia–reperfusion
Submitted 2/11/16, accepted 25/4/17
Published online 31/8/17
Cardiovasc J Afr
2017;
28
: 389–396
www.cvja.co.zaDOI: 10.5830/CVJA-2017-025
Myocardial ischaemia impairs the function and survival of
cardiac myocytes. Current treatment for this condition is
elimination of ischaemia.
1
Although the use of coronary dilator
anti-aggregatory medications to various degrees is the treatment
of choice in the elimination of ischaemia,
2,3
surgical coronary
bypass methods are also used, as laid down in treatment
guidelines.
4-6
Additionally, iloprost is the first line of treatment in
occlusions seen in peripheral artery disease.
7
Iloprost (ILO) is an eicosanoid pharmaceutical agent from
the prostacyclin group.
8
Currently, it is clinically used to unblock
occluded vessels.
9,10
ILO exercises its vasodilatory effect by
preventing platelet aggregation.
8,11
Another vasodilatory agent
that acts via nitric oxide (NO) is sildenafil (SIL).
12
NO levels
increase during ischaemia.
13
During reperfusion, NO levels
are elevated,
13
caused by the vasodilator effect of SIL.
14
The
increased NO levels combine with a superoxide radical (O
2
-
) to
Department of Cardiovascular Surgery, Elazig Education
and Research Hospital, Health Science University, Elazig,
Turkey
Suna Aydin, MD,
cerrah52@hotmail.comDavut Azboy, MD
Zeki Temizturk, MD
Department of Anatomy, School of Medicine, Firat
University, Elazig, Turkey
Suna Aydin, MD
Department of Histology and Embryology, School of
Medicine, Firat University, Elazig, Turkey
Tuncay Kuloglu, MD
Department of Medical Biochemistry (Firat Hormones
Research Group), School of Medicine, Firat University,
Elazig, Turkey
Suleyman Aydin, PhD
Meltem Yardim, MD
Department of Cardiology, Education and Research
Hospital, Istanbul, Turkey
Ali Kemal Kalkan, MD
Department of Cardiovascular Surgery, School of
Medicine, Dicle University, Diyarbakir, Turkey
Mehmet Nesimi Eren, MD