Abstract
Background: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia–reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation. Methods: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated with fingolimod (Group A, n = 30) or saline (Group B, n = 30). Half of the animals in each group (Group A1 and B1, n = 15 each) were sacrificed after 1 h, and the remaining animals (Group A2 and B2) after 24 h of reperfusion. Blood and myocardial tissues were collected for analysis of cardiac features, inflammatory biomarkers, and cell signaling pathways. Results: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes. This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index. Conclusions: Sphingosine1phosphate receptor activation with fingolimod improved cardiac function after cardiac arrest supported with ECLS. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest.
Highlights
Despite rapid advancements in the field of medicine worldwide, sudden cardiac arrest is still a common cause of death in patients with hereditary and ischemic heart diseases [1,2]
The post-resuscitation mortality rate in such patients is about 50% [3]. Both cardiac arrests and cardiopulmonary resuscitation are associated with global myocardial ischemia–reperfusion injury which leads to myocardial dysfunction, resulting in poor prognosis and adverse outcomes [4]
The present study hypothesis was that fingolimod plays a cardioprotective role in global ischemia–reperfusion injury related to sudden cardiac arrest
Summary
Despite rapid advancements in the field of medicine worldwide, sudden cardiac arrest is still a common cause of death in patients with hereditary and ischemic heart diseases [1,2]. The aim of this study was to assess the cardioprotective effect of fingolimod through sphingosine 1-phosphate receptor activation after resuscitation from cardiac arrest during ECLS in a rat model. Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia–reperfusion injury is a leading cause of myocardial dysfunction The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Results: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest
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