Pathophysiology of Ischemia Reperfusion Injury and Use of Fingolimod in Cardioprotection

By Naseer Ahmed

Pathophysiology of Ischemia-Reperfusion Injury and Use of Fingolimod in Cardioprotection is a deep examination into the mechanisms of myocardial ischemiareperfusion injury and role of fingolimod as a cardioprotective agent through its antioxidant, anti-apoptotic and anti-inflammatory effects. Dr. Ahmed explore the physiology and pathophysiology of myocardial metabolism under normal and ischemic conditions and focused on pharmacological cardioprotection. They provide a concise, yet rigorous discussion of Ischemia-Reperfusion Injury, Myocardial Ischemia during Circulatory Arrest, Myocardial Reperfusion, Myocardial Protection related to Ischemia-Reperfusion Injury and Role of Fingolimod in Cardioprotection.
Pathophysiology of Ischemia-Reperfusion Injury and Use of Fingolimod in Cardioprotection is ideal for researchers, cardiovascular scientists, and clinical pharmacologists to further work in this challenging area and apply this knowledge to clinical trials for cardioprotection.

• Provides detailed and critical analysis of the latest research in the field from molecular basis to potential clinical relevance
• Examines the effect of fingolimod/sphingosine 1-phosphate in cardioprotection, pointing to future myocardial preventative strategies

• Language: English
• Publisher: Academic Press
• Release date: May 30, 2019
• ISBN: 9780128182536

Naseer Ahmed

Naseer Ahmed is enthusiastic clinician-scientist who accomplished his PhD (Cardiovascular Sciences) and Postdoctoral fellowship from University of Verona, Verona, Italy. He completed his MBBS degree from Riphah International University, Islamabad, Pakistan. His research interest includes Ischemia-Reperfusion injury, Atherosclerosis & thrombosis and Arrhythmias. He is active research member of Cardiovascular Research lab, Verona and Coordinator of Functional Foods/ Complementary therapies in Cardio-metabolic disorders.

Book preview

pharmacology.

Chapter 1

Introduction to ischemia–reperfusion injury

Abstract

The extent of cell dysfunction, injury, and/or death is dependent on both the intensity and the duration of ischemia. In this aspect, revascularization and restoration of blood flow as soon as possible remains the mainstay of all current therapeutic strategies for ischemia. However, not all organs demonstrate equal susceptibility to ischemia. Moreover, it now seems clear that reperfusion, although necessary to reestablish delivery of oxygen and nutrients to support cell metabolism and remove potentially damaging by-products of cellular metabolism, can elicit pathogenetic processes that exacerbate injury due to ischemia per se and may produce tissue injury in distant organs as a result of mediators released into the bloodstream, draining to vascularized tissues and subsequent delivery to remote organs. There are multiple events involving ischemia reperfusion–related injury.

Keywords

Ischemia; reperfusion injury; revascularization; mediators

Contents

Overview of ischemia/reperfusion 2

Bimodal tissue response to ischemia/reperfusion 5

Ischemia/reperfusion-induced stunning and hibernation versus irreversible cell damage and death 5

Organ-specific susceptibility to ischemia/reperfusion 8

Remote organ injury 13

Pathophysiology of ischemia/reperfusion injury 15

Role of microcirculation in infarct size after ST-segment elevation 16

Therapeutic advancement during last decade 20

Myocardial infraction (ST-segment elevation) 21

Pathophysiology of ischemia/reperfusion injury 22

Preclinical models of myocardial ischemia/reperfusion injury 24

Value of small animal models 25

Large-animal models of myocardial infarction 25

References 26

Further reading 39

Overview of ischemia/reperfusion

The amount of cell dysfunction, damage, and/or death relates to both the intensity and the duration of ischemia. Immediate revascularization and reestablishment of blood flow is still the most important part of all present therapies for ischemia. However, not all organs exhibit the same vulnerability to ischemia. It is evident that reperfusion, is although necessary to reestablish delivery of oxygen and nutrients to support cell metabolism and remove possible harmful by-products of cellular metabolism, can lead to pathogenetic processes that aggravate the damage associated with ischemia. It might damage tissue in distant organs due to the release of mediators into the blood flowing from vascularized tissues and later delivered to remote organs. Also, short bouts of ischemia/reperfusion (I/R) (ischemic preconditioning) before lethal ischemia start cell-survival programs that restrict postischemic damage. This discovery highlights that the reaction to ischemia is bimodal.

Due to ischemia, hypoxia develops which shifts the cell to anaerobic mode. This forms lactate and reduces the pH of the cell due to the collection of hydrogen ions. In compensation, the cell leads to outflow of hydrogen ions in exchange for sodium influx via the Na/H exchanger as a