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Role of Oxidative Stress in Myocardial Ischemia and Infarction

  • Bodh I. JugduttEmail author
  • Bernadine A. Jugdutt
Chapter

Abstract

Myocardial ischemia, ischemia-reperfusion (I/R) and myocardial infarction (MI) are major causes of morbidity and mortality in patients with ischemic heart disease in developed and developing countries worldwide. Much basic and translational research has elucidated how the determinants of myocardial O2 supply and demand modulate cardiac function and dysfunction and underscored how maintaining the balance between O2 supply and demand is essential in therapeutic efforts to interrupt the progression of myocardial ischemia, I/R and MI. Moving forward, while the timely restoration of myocardial blood flow and O2 supply has been shown to save muscle and lives, efforts to prevent I/R injury and reperfusion damage have been frustrating for nearly four decades despite recognition that the major culprit was the reactive oxygen species (ROS) and associated oxidative stress (OXS). Ongoing translational research is therefore focused on providing a broader understanding of the biology of OXS, identifying the key players in ROS regulation and dysregulation, and unravelling pathways and targets for intervention. Such data may allow future development of novel pharmacological treatments and strategies for the limitation and prevention of ROS-induced damage during myocardial ischemia, I/R and MI. If these efforts succeed, the clinical and socioeconomic impact will likely be tremendous.

Keywords

Oxidative stress Mitochondria Apoptosis Necrosis Inflammation Ischemia Infarction Reperfusion Heart failure 

Abbreviations

AMPK

AMP-activated protein kinase

ATP

adenosine triphosphate

BH4

tetrahydrobiopterin

CABG

coronary artery bypass surgery

CaMKII

Ca2+/calmodulin kinase II

cGMP

cyclic guanosine monophosphate

CP

creatine phosphate

DES

drug-eluting stents

DTB

door-to-balloon

ETC

electron transfer chain

FACoA

long-chain fatty-acyl-CoA

FAcarn

long-chain fatty-acyl-carnitine

GIK

glucose-insulin-potassium

GLP-1

anti-diabetic glucagon-like peptide-1

GTP

guanosine triphosphate

H2O2

hydrogen peroxide

HOCl

hypochlorous acid

IL

interleukin

I/R

ischemia-reperfusion

IRA

infarct-related artery

LAD

left anterior descending

LC

left circumflex

LV

left ventricular

MI

myocardial infarction

MPTP

mitochondrial permeability transition pore

MRI

magnetic resonance imaging

MVO2

myocardial oxygen consumption

•NO

nitric oxide

NOO-

NO-derived peroxynitrite

NOS

nitric oxide synthase

NOX

NADPH oxidase

NSTEMI

non-ST segment elevation MI

O2

oxygen

OFRs

oxygen free radicals

OXS

oxidative stress

•OH

hydroxyl radical

PCI

percutaneous coronary intervention

PDH

pyruvate dehydrogenase

PKG

phosphokinase G

PPARs

peroxisome proliferator-activated receptors

PPCI

primary PCI

PTP

permeability transition pore

O2

superoxide anion radical

RCT

randomized clinical trial

RIP3

receptor-interacting protein 3

ROS

reactive oxygen species

SERCA

sarcoendoplasmic reticulum (SR) calcium transport ATPase

SOD

superoxide dismutase

SR

sarcoplasmic reticulum

STEMI

ST-segment elevation MI

TAG

triacyl glycerol

TNF

tumor necrosis factor.

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Cardiology Division, Department of Medicine, Faculty of Medicine, Walter MacKenzie Health Sciences CentreUniversity of AlbertaEdmontonCanada

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