Circulation. 1998;98:1355-1357
(Circulation. 1998;98:1355-1357.)
© 1998 American Heart Association, Inc.
Modes of Myocardial Cell Injury and Cell Death in Ischemic Heart Disease
L. Maximilian Buja, MD;
; Mark L. Entman, MD
From the University of TexasHouston Medical School and the DeBakey
Heart Center, Baylor College of Medicine, Houston, Tex.
Correspondence to L. Maximilian Buja, MD, UT-Houston Medical School, 6431 Fannin St MSB G.010, Houston, TX 77030. E-mail mbuja@dean.med.uth.tmc.edu
Key Words: Editorials apoptosis ischemia myocytes
The manifestations and mechanisms of
myocardial cell injury and cell death in response to impaired
coronary perfusion and thrombosis continue to be the collective
subject of ongoing investigation because of intrinsic scientific
interest and relevance for the diagnosis and treatment of patients with
ischemic heart disease. An extensive body of evidence has
documented the cellular and subcellular alterations that accompany the
progressive reduction in high-energy ATP in response to oxygen
and substrate deprivation affecting all cell types,
including cardiac myocytes.1 2 3 The
characteristic pattern of ischemic cell injury involves fluid
and electrolyte alterations, with loss of K+ and
Mg2+ and accumulation of water,
Na+, Cl-,
H+ (acidosis), and Ca2+;
cytoplasmic, organellar, and cellular swelling with plasma membrane
blebbing; and margination and clumping of nuclear chromatin. These
cellular changes are due to progressive impairment of membrane
composition, structure, and function.1 The
transition from reversible to irreversible injury is characterized by
the development of a severe membrane permeability defect that allows
the unregulated influx of divalent and trivalent cations, including
calcium.1 Subsequently, the swollen cells develop
physical defects (holes) in their cell membranes and rupture. These
features of cell injury with cell swelling have been shown to involve
cardiac myocytes subjected to hypoxia in vitro and cardiac
muscle during the evolution of myocardial infarction in
vivo.1 3 Myocardium undergoing
ischemic death ultimately exhibits some variant of coagulation
necrosis and elicits an inflammatory response with an initial influx of
neutrophils.3 The underlying membrane damage
to ischemic myocytes is the basis for the . . . [Full Text of this Article]
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|

|
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45(3):
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|
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45(3):
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|
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|

|
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November 2, 1999;
20(22):
1619 - 1629.
[PDF]
|
 |
|

|
 |

|
 |
 
B. C. Yang, D. S. Zander, and J. L. Mehta
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291(2):
733 - 738.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
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November 1, 1999;
44(2):
232 - 241.
[Full Text]
[PDF]
|
 |
|

|
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|
 |
 
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October 29, 1999;
85(9):
856 - 866.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Circ. Res.,
July 23, 1999;
85(2):
147 - 153.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Postmitochondrial regulation of apoptosis during heart failure
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July 6, 1999;
96(14):
7614 - 7616.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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June 1, 1999;
99(21):
2757 - 2764.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
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Circ. Res.,
May 14, 1999;
84(9):
1007 - 1019.
[Abstract]
[Full Text]
[PDF]
|
 |
|