Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart

Mohsen Karimi; Christopher A Caldarone; Jeffrey L Segar; Elesa W Barner; Lixing Wang; Thomas D Scholz; Christopher E Mascio; James M Hammel; Changqing Du

doi:10.1016/j.athoracsur.2004.04.031

Back

Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart

Journal article

Peer reviewed

Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart

Mohsen Karimi, Christopher A Caldarone, Jeffrey L Segar, Elesa W Barner, Lixing Wang, Thomas D Scholz, Christopher E Mascio, James M Hammel and Changqing Du

The Annals of thoracic surgery, Vol.78(3), pp.948-955

2004

DOI: 10.1016/j.athoracsur.2004.04.031

PMID: 15337026

View Online

Abstract

In the early postoperative period, the neonatal myocardium undergoes sparse apoptotic cell loss (∼ 1% of myocytes). Because apoptosis is preceded by events associated with mitochondrial dysfunction, the fraction of myocytes with preapoptotic mitochondrial changes has important clinical implications (eg, postoperative myocardial dysfunction). My colleagues and I therefore hypothesized that postoperative apoptotic myocytes represent a tip of the iceberg, with more myocytes upstream with apoptosis-related mitochondrial dysfunction (ARMD). Neonatal lambs underwent cardiopulmonary bypass, 60 minutes of cardioplegic arrest, and 6 hours of recovery (cardiopulmonary bypass with cardioplegic arrest [CPB+CP]; n = 5) and were compared with nonbypass controls (non-CPB; n = 5). Myocardium (left ventricle [LV] and right ventricle [RV]) was examined by using terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, electron microscopy, immunohistochemistry, Western blot, and isolated mitochondrial oxygen consumption measurement. TUNEL-positive nuclei and electron microscopy–confirmed mitochondrial structural changes were more common in CPB+CP than non-CPB myocardium and were more common in the LV than RV ( p = 0.0016). Bax (a proapoptotic mediator) translocated from the cytosol to the mitochondria (LV > RV; p < 0.05). Immunohistochemistry demonstrated diffuse mitochondrial loss of cytochrome c that was consistent with outer mitochondrial membrane permeabilization (LV > RV > non-CPB). Permeabilization was further demonstrated by augmentation of oxygen consumption in isolated mitochondria after administration of exogenous cytochrome c. The mitochondrial oxygen consumption boost was 57% for CPB+CP:LV; 23% for CPB+CP:RV; and 18% and 17% for non-CPB:LV and non-CPB:RV, respectively ( p < 0.01, CPB+CP:LV vs other groups). ARMD is much greater than the prevalence of TUNEL-positive myocytes in postoperative neonatal myocardium. Greater LV vulnerability may represent a relationship between increased afterload and ARMD. These changes are consistent with the early postoperative myocardial dysfunction commonly reported after neonatal cardiac operations.

First Quarter

Details

Title: Subtitle: Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart
Creators: Mohsen Karimi - Division of Cardiovascular Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Christopher A Caldarone - Division of Cardiovascular Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Jeffrey L Segar - Division of Cardiothoracic Surgery, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Elesa W Barner - Division of Cardiovascular Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Lixing Wang - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA
Thomas D Scholz - Division of Cardiothoracic Surgery, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Christopher E Mascio - Division of Cardiovascular Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
James M Hammel - Division of Cardiovascular Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Changqing Du - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: The Annals of thoracic surgery, Vol.78(3), pp.948-955
DOI: 10.1016/j.athoracsur.2004.04.031
PMID: 15337026
NLM abbreviation: Ann Thorac Surg
ISSN: 0003-4975
eISSN: 1552-6259
Publisher: Elsevier Inc
Language: English
Date published: 2004
Academic Unit: Cardiology; Stead Family Department of Pediatrics; Surgery; Child and Community Health; Cardiothoracic Surgery
Record Identifier: 9984093339902771

Metrics

25 Record Views

22 Times Cited - Web of Science