Cardiovasc Drugs Ther. 1991 Mar;5:249-68. doi: 10.1007/BF00054747.

Oxygen-derived free radicals and myocardial reperfusion injury: an overview.

Cardiovascular drugs and therapy

R Bolli

PMID: 1854667 DOI: 10.1007/BF00054747

Abstract

Reperfusion of acutely ischemic myocardium is associated with various distinctive pathophysiologic derangements, which are collectively referred to as reperfusion injury. Among these, three have been attributed to oxygen radicals: a) arrhythmias, b) transient mechanical dysfunction ("stunning"), and c) cell death. a) Reperfusion-induced arrhythmias. Although the precise mechanism for reperfusion arrhythmias remains to be determined, considerable evidence suggests that oxygen radicals play an important pathogenetic role in these rhythm disturbances. b) Transient mechanical dysfunction ("myocardial stunning"). Studies suggest that this abnormality is caused by events occurring in the initial seconds of reperfusion, and therefore represents a manifestation of sublethal, reversible reperfusion injury. Although our understanding of the mechanism of myocardial stunning is still fragmentary, there is overwhelming evidence for a pathogenetic role of oxygen radicals. c) Cell death. The evidence that reperfusion causes extension of the infarct produced by the antecedent ischemia is highly controversial. Although several studies have reported reduction of infarct size with antioxidants applied at the time of reperfusion, numerous other investigations have failed to reproduce these results. At present, there is no obvious explanation for this discrepancy. What is clear is that short-term administration of antioxidants at the time of reperfusion will not produce sustained limitation of infarct size. However, the possibility that long-term administration of antioxidants will produce sustained limitation of infarct size merits further consideration. In conclusion, there is strong evidence that the generation of oxygen radicals upon reperfusion plays an important pathogenetic role in two manifestations of reperfusion injury, namely, arrhythmias and stunning. Intense controversy persists regarding whether oxygen radicals contribute to extending cell death upon reperfusion and whether reperfusion in itself causes cell death. On the basis of the evidence available at this time, oxygen radicals appear to be important in the genesis of relatively mild, sublethal forms of myocellular damage, but their role in the genesis of lethal myocellular injury remains to be established.

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References

1. Circ Res. 1990 May;66(5):1294-301 - PubMed
2. Circ Res. 1990 May;66(5):1268-76 - PubMed
3. Circ Res. 1988 Nov;63(5):944-59 - PubMed
4. Am J Physiol. 1987 Dec;253(6 Pt 2):H1372-80 - PubMed
5. Circulation. 1982 Aug;66(2 Pt 2):I85-92 - PubMed
6. Free Radic Res Commun. 1990;9(3-6):169-80 - PubMed
7. Circulation. 1989 Nov;80(5):1432-48 - PubMed
8. Circ Res. 1984 Mar;54(3):277-85 - PubMed
9. J Mol Cell Cardiol. 1985 Feb;17(2):145-52 - PubMed
10. J Am Coll Cardiol. 1989 Jan;13(1):185-94 - PubMed
11. J Mol Cell Cardiol. 1987 Mar;19(3):289-302 - PubMed
12. Circulation. 1988 Mar;77(3):685-95 - PubMed
13. J Lab Clin Med. 1987 Jul;110(1):13-30 - PubMed
14. Am Heart J. 1990 Apr;119(4):807-15 - PubMed
15. Am J Physiol. 1987 Sep;253(3 Pt 2):H709-11 - PubMed
16. J Mol Cell Cardiol. 1978 Jul;10 (7):641-68 - PubMed
17. J Thorac Cardiovasc Surg. 1982 Jun;83(6):830-9 - PubMed
18. Circ Res. 1987 Nov;61(5):757-60 - PubMed
19. Am J Cardiol. 1976 Nov 4;38(5):599-606 - PubMed
20. Circulation. 1988 Jul;78(1):202-13 - PubMed
21. Proc Natl Acad Sci U S A. 1987 Aug;84(16):6005-9 - PubMed
22. Circ Res. 1989 Oct;65(4):1112-24 - PubMed
23. Circ Res. 1988 Aug;63(2):351-60 - PubMed
24. Circulation. 1989 Oct;80(4):1049-62 - PubMed
25. J Mol Cell Cardiol. 1988 Jan;20(1):35-45 - PubMed
26. Am J Physiol. 1989 Feb;256(2 Pt 2):H341-51 - PubMed
27. Circulation. 1985 Aug;72(2):413-30 - PubMed
28. Circulation. 1985 Oct;72(4):915-21 - PubMed
29. Circ Res. 1989 Oct;65(4):1045-56 - PubMed
30. Prog Cardiovasc Dis. 1987 Jul-Aug;30(1):23-44 - PubMed
31. Prog Cardiovasc Dis. 1986 May-Jun;28(6):449-62 - PubMed
32. Circ Res. 1989 Jan;64(1):86-96 - PubMed
33. Am J Physiol. 1986 Nov;251(5 Pt 2):H1045-55 - PubMed
34. Circulation. 1986 Mar;73(3):518-24 - PubMed
35. Am J Physiol. 1989 Feb;256(2 Pt 2):H368-74 - PubMed
36. J Am Coll Cardiol. 1989 Apr;13(5):1155-63 - PubMed
37. J Thorac Cardiovasc Surg. 1986 Aug;92(2):264-71 - PubMed
38. Am J Physiol. 1986 Apr;250(4 Pt 2):H595-9 - PubMed
39. J Biol Chem. 1986 Apr 15;261(11):4948-55 - PubMed
40. J Clin Invest. 1975 Oct;56(4):978-85 - PubMed
41. Circulation. 1987 Sep;76(3):678-86 - PubMed
42. Free Radic Biol Med. 1989;7(1):45-52 - PubMed
43. Circulation. 1985 Jan;71(1):165-75 - PubMed
44. Circulation. 1986 Dec;74(6):1424-33 - PubMed
45. Circ Res. 1985 Jun;56(6):895-8 - PubMed
46. J Biol Chem. 1988 Jan 25;263(3):1353-7 - PubMed
47. Am J Physiol. 1988 Nov;255(5 Pt 2):H1188-98 - PubMed
48. J Cardiovasc Pharmacol. 1986 Sep-Oct;8(5):978-88 - PubMed
49. Circ Res. 1987 Jul;61(1):20-8 - PubMed
50. J Mol Cell Cardiol. 1985 Nov;17(11):1029-42 - PubMed
51. Circulation. 1983 Aug;68(2 Pt 2):I25-36 - PubMed
52. Circulation. 1986 May;73(5):1065-76 - PubMed
53. Basic Res Cardiol. 1988 Nov-Dec;83(6):602-10 - PubMed
54. Circ Res. 1989 Aug;65(2):526-30 - PubMed
55. Surgery. 1987 Aug;102(2):334-40 - PubMed
56. Am J Physiol. 1990 Feb;258(2 Pt 2):H369-80 - PubMed
57. J Mol Cell Cardiol. 1989 Jul;21(7):691-5 - PubMed
58. Am J Physiol. 1988 Jan;254(1 Pt 2):H102-14 - PubMed
59. Circulation. 1982 Dec;66(6):1146-9 - PubMed
60. Acta Physiol Scand Suppl. 1986;548:39-46 - PubMed
61. J Mol Cell Cardiol. 1984 Jun;16(6):497-518 - PubMed
62. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7793-7 - PubMed
63. J Mol Cell Cardiol. 1986 Oct;18(10):1077-84 - PubMed
64. Circulation. 1987 Jan;75(1):282-91 - PubMed
65. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1404-7 - PubMed
66. J Biol Chem. 1987 Jul 15;262(20):9895-901 - PubMed
67. Am J Physiol. 1984 Jun;246(6 Pt 2):H776-83 - PubMed
68. Circulation. 1987 Jun;75(6 Pt 2):V25-33 - PubMed
69. J Mol Cell Cardiol. 1985 May;17(5):485-93 - PubMed
70. J Clin Invest. 1987 Mar;79(3):950-61 - PubMed
71. Cardiovasc Res. 1989 Apr;23(4):340-50 - PubMed
72. Circulation. 1988 Aug;78(2):473-80 - PubMed
73. J Cardiovasc Pharmacol. 1989 Feb;13(2):258-64 - PubMed
74. Circ Res. 1984 Oct;55(4):545-8 - PubMed
75. Circ Res. 1989 Apr;64(4):665-75 - PubMed
76. J Am Coll Cardiol. 1983 Apr;1(4):1047-55 - PubMed
77. Circulation. 1985 May;71(5):1069-75 - PubMed
78. Circulation. 1988 Jun;77(6 Pt 2):I30-9 - PubMed
79. J Clin Invest. 1988 Sep;82(3):920-7 - PubMed
80. Am J Physiol. 1989 Aug;257(2 Pt 2):H375-85 - PubMed
81. Circulation. 1989 Dec;80(6):1828-36 - PubMed
82. Circulation. 1989 Nov;80(5 Pt 2):III14-8 - PubMed
83. J Mol Cell Cardiol. 1988 Mar;20(3):213-23 - PubMed
84. Am J Physiol. 1987 Feb;252(2 Pt 2):H252-7 - PubMed
85. J Mol Cell Cardiol. 1989 Mar;21(3):263-7 - PubMed
86. Circ Res. 1983 Aug;53(2):235-47 - PubMed
87. Cardiovasc Drugs Ther. 1987 Aug;1(2):133-9 - PubMed
88. Am J Physiol. 1988 Jul;255(1 Pt 2):H138-43 - PubMed
89. N Engl J Med. 1985 Jan 17;312(3):159-63 - PubMed
90. Cardiovasc Res. 1987 Oct;21(10):755-60 - PubMed
91. J Thorac Cardiovasc Surg. 1986 Feb;91(2):281-9 - PubMed
92. Am J Physiol. 1988 Jun;254(6 Pt 2):H1133-41 - PubMed
93. J Am Coll Cardiol. 1988 Mar;11(3):614-23 - PubMed
94. Free Radic Biol Med. 1988;4(1):45-50 - PubMed
95. J Am Coll Cardiol. 1986 Mar;7(3):580-9 - PubMed
96. Circulation. 1983 Jul;68(1):170-82 - PubMed
97. Cardiovasc Res. 1976 Nov;10(6):678-86 - PubMed
98. Circulation. 1983 Aug;68(2 Pt 2):I8-15 - PubMed
99. Circ Res. 1989 Sep;65(3):607-22 - PubMed
100. Circulation. 1989 May;79(5):1137-42 - PubMed
101. Free Radic Biol Med. 1988;4(1):25-30 - PubMed
102. Circ Res. 1983 Aug;53(2):248-63 - PubMed
103. Basic Res Cardiol. 1987 Sep-Oct;82(5):486-92 - PubMed
104. Biochem J. 1984 Apr 1;219(1):1-14 - PubMed
105. J Mol Cell Cardiol. 1988 Nov;20(11):1009-24 - PubMed
106. Pharmacology. 1982;24(2):118-22 - PubMed
107. Circ Res. 1987 Dec;61(6):834-46 - PubMed
108. Circulation. 1989 Nov;80(5 Pt 2):III30-5 - PubMed
109. Basic Res Cardiol. 1987 Mar-Apr;82(2):146-58 - PubMed
110. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2786-9 - PubMed
111. J Clin Invest. 1989 Jun;83(6):1800-9 - PubMed
112. J Clin Invest. 1984 Oct;74(4):1456-64 - PubMed
113. Am J Physiol. 1978 Jun;234(6):H653-9 - PubMed
114. Circulation. 1987 Aug;76(2):458-68 - PubMed
115. Circ Res. 1986 Mar;58(3):331-40 - PubMed
116. Am J Physiol. 1990 Sep;259(3 Pt 2):H889-901 - PubMed
117. Circ Res. 1983 Nov;53(5):584-91 - PubMed
118. Circ Res. 1984 Jul;55(1):120-4 - PubMed
119. Circulation. 1987 Jun;75(6):1237-48 - PubMed
120. J Clin Invest. 1988 Aug;82(2):476-85 - PubMed
121. J Am Coll Cardiol. 1988 Jul;12(1):209-17 - PubMed
122. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):158-66 - PubMed
123. Circulation. 1989 Jan;79(1):143-53 - PubMed
124. Ann Intern Med. 1988 Apr;108(4):626-8 - PubMed
125. J Am Coll Cardiol. 1990 Mar 1;15(3):737-47 - PubMed
126. J Cardiovasc Pharmacol. 1988 Jan;11(1):36-44 - PubMed
127. J Thorac Cardiovasc Surg. 1983 Aug;86(2):262-72 - PubMed
128. Basic Res Cardiol. 1988 Mar-Apr;83(2):141-8 - PubMed
129. Am J Physiol. 1987 Mar;252(3 Pt 2):H566-77 - PubMed
130. Am J Physiol. 1986 Mar;250(3 Pt 2):H372-7 - PubMed
131. J Am Coll Cardiol. 1986 Nov;8(5):1161-8 - PubMed
132. Circ Res. 1987 May;60(5):700-7 - PubMed
133. J Biol Chem. 1984 Feb 25;259(4):2135-43 - PubMed
134. J Am Coll Cardiol. 1989 Apr;13(5):1176-83 - PubMed
135. Circ Res. 1986 Jan;58(1):148-56 - PubMed
136. Cardiovasc Res. 1987 Jul;21(7):492-9 - PubMed
137. Cardiovasc Res. 1986 Aug;20(8):597-603 - PubMed
138. Circulation. 1989 Dec;80(6 Suppl):IV17-22 - PubMed
139. Am J Physiol. 1986 Dec;251(6 Pt 2):H1225-31 - PubMed
140. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4695-9 - PubMed

Substances

• Free Radicals
• Oxygen

MeSH terms

• Animals
• Arrhythmias, Cardiac / etiology
• Biomechanical Phenomena
• Free Radicals
• Myocardial Infarction / etiology
• Myocardial Reperfusion Injury / complications
• Myocardial Reperfusion Injury / metabolism
• Myocardial Reperfusion Injury / physiopathology
• Oxygen / metabolism

Publication Types

• Journal Article
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.
• Review

Grant support

• HL-36277/HL/NHLBI NIH HHS/United States
• HL-42267/HL/NHLBI NIH HHS/United States
• HL-43151/HL/NHLBI NIH HHS/United States

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