168 Cardioprotective role of fingolimod in ischemia-reperfusion injury by activation of akt/erk pathways in rat model

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Abstract

Background and purpose

Ischaemic Heart Diseases (IHD) are the most common cause of morbidity and mortality. Incidence and prevalence are continuously growing. There is an escalating risk for revascularisation or resuscitation in patients with IHD. Recently, it has been reported that a sphingosine 1-phosphate receptor agonist play an anti-apoptotic and anti-inflammatory role in the ischemia-reperfusion injury.

Objectives

The aim of our study is to investigate the cardioprotective effects of sphingosine 1-phosphate receptor agonist fingolimod (FTY720) on global ischemia-reperfusion injury related to the cardiac surgery.

Methods

In our experimental study, global ischemia-reperfusion was achieved by cardiopulmonary bypass by cardioplegic arrest on ventilated male Sprague-Dawley rats (300–350 g). The global ischaemic period lasted 10 min in the cardioplegic arrest while reperfusion times were maintained for 60 min and 24 hours. ECG monitoring was done using AD instrument and using Millar catheter, heart rate, systolic and diastolic pressures were recorded and mean arterial pressure was calculated. The statistical significance was considered at P 0.05.

Results

The myocardial protection was observed in the group treated with Fingolimod as compared to control groups. Reduced frequency of apoptotic cells and inflammatory mediators were found in the treated group. The level of adenylates was preserved in the treated group as compared to controls (94%, 61% respectively)(p0.001). Reactive Oxygen Species (ROS) were attenuated in the fingolimod-treated group. Fingolimod treatment improved systolic and diastolic ventricular pressures and contractility strength (p0.005).

Conclusions

The intravenous administration of fingolimod in global ischemia-reperfusion was cardioprotective. Fingolimod cardioprotection appears to be mediated through preservation of high energy phosphates, reduction in oxidative stress, inhibition of apoptosis and inflammation leading to improved cardiac functions.

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