Apoptosis is involved in the mechanism of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest

被引:21
作者
Gu, Wei [1 ]
Li, Chun Sheng [1 ]
Yin, Wen Peng [1 ]
Guo, Zhi Jun [1 ]
Hou, Xiao Min [1 ]
Zhang, Da [1 ]
机构
[1] Capital Med Univ, Beijing Chaoyang Hosp, Dept Emergency Med, Beijing, Peoples R China
关键词
VENTRICULAR-FIBRILLATION; RESUSCITATION; CARDIOPULMONARY; HYPOTHERMIA; CASPASE-3; HEART;
D O I
10.1016/j.ajem.2012.04.031
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Postresuscitation myocardial dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. This study investigated whether caspase 3-mediated apoptosis is activated in the heart after postresuscitation myocardial dysfunction. Methods: After pigs were subjected to 8 minutes of electrically induced cardiac arrest (CA), standard cardiopulmonary resuscitation was performed. Animals in the post-return of spontaneous circulation (ROSC) group were randomly assigned to be killed (n = 6 per group) at 12 and 24 hours after ROSC, and myocardial specimens were analyzed with electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Results: Myocardial function was significantly impaired after ROSC. Expression of Bcl-2, Bax, and caspase 3 protein was markedly increased in the post-ROSC group compared with the sham-operated group (P < .05) at 12 and 24 hours after ROSC, whereas Bcl-2/Bax was significantly reduced in the post-ROSC group compared with the sham-operated group (P < .05). The messenger RNA levels of caspase 3 were significantly elevated at 12 and 24 hours after ROSC, and increases in caspase 3 activity indicated activation of the mitochondrial apoptotic pathway. Typical apoptotic nuclei were observed in cardiomyocytes 24 hours after ROSC. More apoptotic cells were observed in animals that had undergone CA compared with sham-operated animals (P < .05). Conclusion: Caspase 3-mediated apoptosis may be one of the main pathologic mechanisms of postresuscitation myocardial injury in a porcine model of CA. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:2039 / 2045
页数:7
相关论文
共 15 条
[1]   Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure [J].
Abbate, A ;
Biondi-Zoccai, GGL ;
Bussani, R ;
Dobrina, A ;
Camilot, D ;
Feroce, F ;
Rossiello, R ;
Baldi, F ;
Silvestri, F ;
Biasucci, LM ;
Baldi, A .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 41 (05) :753-760
[2]  
ARENDS MJ, 1990, AM J PATHOL, V136, P593
[3]   The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions [J].
Borner, C .
MOLECULAR IMMUNOLOGY, 2003, 39 (11) :615-647
[4]   Perspective - Hypothermia to protect the brain [J].
Curfman, GD .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (08) :546-546
[5]   Effects of norepinephrine on kidney in a Swine model of cardiopulmonary resuscitation [J].
Han, Yi ;
Li, Chun-sheng ;
Su, Zhi-yu ;
Lu, Yi ;
Wang, Sheng-qi .
AMERICAN JOURNAL OF EMERGENCY MEDICINE, 2011, 29 (07) :731-737
[6]  
KERN KB, 1994, CIRCULATION, V90, P5
[7]  
Louise M, 2010, AM J EMERG MED, V28, P543
[8]   Essential myosin light chain as a target for caspase-3 in failing myocardium [J].
Moretti, A ;
Weig, HJ ;
Ott, T ;
Seyfarth, M ;
Holthoff, HP ;
Grewe, D ;
Gillitzer, A ;
Bott-Flügel, L ;
Schömig, A ;
Ungerer, M ;
Laugwitz, KL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (18) :11860-11865
[9]   Post-Cardiac Arrest Syndrome Epidemiology, Pathophysiology, Treatment, and Prognostication A Consensus Statement From the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council [J].
Neumar, Robert W. ;
Nolan, Jerry P. ;
Adrie, Christophe ;
Aibiki, Mayuki ;
Berg, Robert A. ;
Boettiger, Bernd W. ;
Callaway, Clifton ;
Clark, Robert S. B. ;
Geocadin, Romergryko G. ;
Jauch, Edward C. ;
Kern, Karl B. ;
Laurent, Ivan ;
Longstreth, W. T., Jr. ;
Merchant, Raina M. ;
Morley, Peter ;
Morrison, Laurie J. ;
Nadkarni, Vinay ;
Peberdy, Mary Ann ;
Rivers, Emanuel P. ;
Rodriguez-Nunez, Antonio ;
Sellke, Frank W. ;
Spaulding, Christian ;
Sunde, Kjetil ;
Hoek, Terry Vanden .
CIRCULATION, 2008, 118 (23) :2452-2483
[10]   Regional variation in out-of-hospital cardiac arrest incidence and outcome [J].
Nichol, Graham ;
Thomas, Elizabeth ;
Callaway, Clifton W. ;
Hedges, Jerris ;
Powell, Judy L. ;
Aufderheide, Tom P. ;
Rea, Tom ;
Lowe, Robert ;
Brown, Todd ;
Dreyer, John ;
Davis, Dan ;
Idris, Ahamed ;
Stiell, Ian .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 300 (12) :1423-1431