Free-Radical Mechanisms of Ischemic and Reperfusion Injuries of Various Organs

by M. V. Bilenko

Overview

In this book, the author's experimental results, plus analysis of published data from 1970 through 1999, are used as the basis for analyzing pathogenesis of acute ischemic and reperfusion injuries from the membranological standpoint. Attention is concentrated on the interaction between free-radical reactions and other factors responsible for ischemic and reperfusion injuries. Responses to ischemia and reperfusion of important organs are compared in terms of differences in sensitivity to oxygen deficiency, the development of collateral blood flow, tissue metabolism, and provision with free- radical-generating and antioxidant systems. The role of macrophages and endothelial cells in free radical production is analyzed to reveal a relationship between the accumulation of products of disturbed liquid metabolism and local or generalized postischemic hemodynamic disorders in organs and the entire organism. Bilenko is head of the Antiischemic and Antiradical Drug Department of the Institute of Biomedical Chemistry at the Russian Academy of Medical Sciences.

Annotation c. Book News, Inc., Portland, OR (booknews.com)

Product Details

ISBN-13:	9781560728009
Publisher:	Nova Science Publishers, Incorporated
Publication date:	10/28/2001
Pages:	382
Product dimensions:	7.63(w) x 10.70(h) x 1.10(d)

Table of Contents

	Preface	xi
	Introduction	xiii
	Abbreviations	xvii
Chapter 1	Circulatory and Oxygen-Supply Disorders During Acute Ischemia and After Reperfusion of Organs	1
1.1	Circulatory and Oxygen-Supply Disorders in Organs Affected by Different Types of Acute Ischemia	1
1.2	Circulatory and Oxygen-Supply Disorders in Organs during the Reperfusion Period	9
1.3	Conclusions	18
Chapter 2	Structural and Functional Membrane Disorders During Ischemia and After Reperfusion of Organs	21
2.1	Disturbances of the Barrier Function of Membranes	23
2.2	Changes in the Lipid Composition of Membranes	30
2.3	Changes in Membrane Protein Activity	37
2.4	Conclusions	44
Chapter 3	Disorders of Adenine Nucleotide Metabolism During Acute Ischemia and After Reperfusion of Organs	47
3.1	Disorders of Adenine Nucleotide Production, Transport, and Utilization	47
3.2	Changes in Contents and Composition of Adenine Nucleotides and Their Critical Levels	56
3.3	Effects of Disorders of Adenine Nucleotide Metabolism on Functions and Structure of Membranes	64
3.4	Conclusions	68
Chapter 4	Intensification of Hydrolysis of Membrane Phospholipids and Disorders of Free Fatty Acid Metabolism During Acute Ischemia and After Reperfusion of Organs	69
4.1	Intensification of Membrane Phospholipids Hydrolysis	69
4.2	Increasing Contents of Free Fatty Acids and Intermediate Products of Their Oxidation, and Their Damaging Effect on Membranes	72
4.3	Accumulation of Lysophospholipids and Their Damaging Effect on Membranes	76
4.4	Increasing Content of Arachidonic Acid Metabolism Products and their Protective and Damaging Effects on Membranes	77
4.5	Possible Factors Promoting Phospholipid Hydrolysis, and Mechanisms of the Damaging Effect Exerted by Its Products on Membranes	81
4.6	Conclusions	85
Chapter 5	Intensification of Lipid Peroxidation During Acute Ischemia and After Reperfusion of Organs	87
5.1	Methods for Determining ROS and LPO Products in Ischemic and Reperfused Organs	88
5.2	Estimating LPO Activity in Ischemic and Reperfused Organs	92
5.3	Comparative Analysis of Changes in LPO Activity in Organs and Membranes Differing in Sensitivity to Ischemia	111
5.4	Some Mechanisms Responsible for the Damaging Effect of LPO on Membranes	119
5.5	Conclusions	122
Chapter 6	Effect of Different Blood Oxygen Content in Early Postischemic Period on the Severity of Reperfusion Injury in Organs	125
6.1	Effects of Different Blood Oxygen Content in the Early Postischemic Period on Circulatory, Structural, and Functional Disorders in Reperfused Organs	127
6.2	Effects of Different Blood Oxygen Content in the Early Postischemic Period on the Intensity of Lipid Peroxidation in Reperfused Organs	136
6.3	Possible Mechanisms Responsible for Effects of Different Blood Oxygen Content in the Early Postischemic Period on the Severity of Reperfusion Injuries in Organs	139
6.4	The Use of Methods for Raising and Lowering Blood Oxygen Content in Experiments and Clinical Practice	142
6.5	Conclusions	144
Chapter 7	Role of Lipid Peroxidation in the Pathogenesis of Ischemic Shock	145
7.1	Accumulation of Lipid Peroxidation Products in Blood and Different Organs upon Ischemic Shock	146
7.2	Role of Lipid Peroxidation in Animal Mortality upon Ischemic Shock	149
7.3	Role of Lipid Peroxidation-induced Disturbances of the Hepatic Cytochrome P-450-dependent Monooxygenase System in Animal Mortality upon Ischemic Shock	151
7.4	Role of Lipid Peroxidation-induced Disturbances of Coronary Circulation and Myocardial Contractile Function in Animal Mortality upon Ischemic Shock	153
7.5	Conclusions	156
Chapter 8	Vasoactive and Cardiotropic Effects of Circulating Unoxidized and Oxidized Free Fatty Acids and Phospholipids and Their Role in the Pathogenesis of Local and Systemic Circulatory Disorders During Acute Ischemia and After Reperfusion of Organs	159
8.1	Vasoactive Effect of Circulating Unoxidized and Oxidized Free Fatty Acids	159
8.2	Vasoactive and Cardiotropic Effects of Circulating Unoxidized and Oxidized Phospholipids	160
8.3	Possible Mechanisms of the Vasoactive and Cardiotropic Effects of Circulating Unoxidized and Oxidized Free Fatty Acids and Phospholipids	166
8.4	Conclusions	170
Chapter 9	Role of Cytokines and Growth Factors, Free Radicals, and Lipid Peroxidation Products in DNA Damage and Repair During Acute Ischemia and After Reperfusion of Organs	171
9.1	DNA Damage and Repair during Acute Ischemia and after Reperfusion of Organs	173
9.2	Roles of Cytokines and Growth Factors in DNA Damage and Repair during Acute Ischemia and after Reperfusion of Organs	177
9.3	Role of Free Radicals and Lipid Peroxidation in DNA Damage and Repair during Acute Ischemia and after Reperfusion of Organs	184
9.4	Conclusions	190
Chapter 10	Possible Mechanisms of Intensification of Lipid Peroxidation during Acute Ischemia and After Reperfusion of Organs	193
10.1	Conditions Prerequisite to Lipid Peroxidation in Membranes	193
10.2	Sources of Reactive Oxygen Species	196
10.3	Changes in the Activity of Antioxidant Enzyme Systems	217
10.4	Changes in the Contents of Water- and Fat-soluble Nonenzymatic Prooxidants and Antioxidants	224
10.5	Conclusions	236
Chapter 11	The Use of Free-Radical Inhibitors for Protecting Organs Against Ischemic and Reperfusion Injuries	243
11.1	Natural and Synthetic Antiradical Drugs	244
11.2	Antioxidant Enzymes and Scavengers of Reactive Oxygen Species	259
11.3	Chelators and Reducers of Transition Metals	261
11.4	Inhibitors of Enzyme Systems Involved in Production of Reactive Oxygen Species	265
11.5	Other Antiischemic and Antiradical Agents	276
11.6	Conclusions	278
	References	281
	Index	357