Cardiovascular Journal of Africa: Vol 28 No 6 (November/December 2017)

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;

: 389–396

www.cvja.co.za

DOI: 10.5830/CVJA-2017-025

Myocardial ischaemia impairs the function and survival of

cardiac myocytes. Current treatment for this condition is

elimination of ischaemia.

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.

Iloprost (ILO) is an eicosanoid pharmaceutical agent from

the prostacyclin group.

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).

NO levels

increase during ischaemia.

During reperfusion, NO levels

are elevated,

caused by the vasodilator effect of SIL.

The

increased NO levels combine with a superoxide radical (O

) to

Department of Cardiovascular Surgery, Elazig Education

and Research Hospital, Health Science University, Elazig,

Turkey

Suna Aydin, MD,

cerrah52@hotmail.com

Davut 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