Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs

Mohsen Karimi; Li Xing Wang; Thomas D Scholz; James M Hammel; Jeffrey L Segar; Christopher E Mascio; Mohamed Abdulhamid; Elesa W Barner; Wei Gen Li; Scott D Niles; Christopher A Caldarone

doi:10.1016/j.jtcvs.2003.07.052

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Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs

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Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs

Mohsen Karimi, Li Xing Wang, Thomas D Scholz, James M Hammel, Jeffrey L Segar, Christopher E Mascio, Mohamed Abdulhamid, Elesa W Barner, Wei Gen Li, Scott D Niles, …

The Journal of thoracic and cardiovascular surgery, Vol.127(2), pp.490-497

2004

DOI: 10.1016/j.jtcvs.2003.07.052

PMID: 14762359

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Abstract

Apoptosis is a mechanism for deletion of injured or obsolete cells that is distinct from necrosis and mediated by mitochondrial release of cytochrome c caspase activation. Because myocardial apoptosis is a part of normal fetal and postnatal maturation, we hypothesize that neonatal myocardium is more vulnerable to undergo myocardial apoptosis than mature myocardium after cardioplegic arrest. Newborn and mature lambs (n = 5 in each group) underwent cardiopulmonary bypass, antegrade crystalloid hyperkalemic cardioplegic arrest for 60 minutes, and a 6-hour recovery period. Myocardium was examined by using terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–digoxigenin nick end labeling (TUNEL), Western blotting, in vitro kinase assays, and fluorometric assays of the activity of caspases 3, 8, and 9. Myocardium from nonoperated control subjects (n = 5 in each age group) was also obtained. More TUNEL-positive nuclei were present in the newborn postcardioplegic myocardium ( P = .04). Caspase 3, 8, and 9 activities were 1.6-fold, 1.5-fold, and 1.4-fold greater in the newborn postcardioplegic myocardium ( P = .04, P = .01, and P = .01, respectively). The Bax/Bcl-2 ratio was higher in the newborn postcardioplegic myocardium ( P = .04). Apoptosis signal-regulating kinase 1 activity and cleaved caspase 3 levels were higher in the newborn postcardioplegic myocardium ( P = .02 and P = .009). Mitochondrial release of cytochrome c was greater in the newborn postcardioplegic myocardium ( P = .009). The increased Bax/Bcl-2 ratio in the newborn myocardium suggests a proapoptotic state that is manifested by greater TUNEL staining, cytochrome c release, and cleavage of caspase 3. Increased apoptosis signal-regulating kinase 1 activity suggests greater oxidative stress, immature mechanisms to ameliorate oxidative stress, or both in the neonatal myocardium. Mitochondrial release of cytochrome c suggests that apoptosis-related mitochondrial dysfunction might contribute to early postoperative myocardial dysfunction in the neonate.

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Title: Subtitle: Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs
Creators: Mohsen Karimi - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Li Xing Wang - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Thomas D Scholz - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA
James M Hammel - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Jeffrey L Segar - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA
Christopher E Mascio - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Mohamed Abdulhamid - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Elesa W Barner - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Wei Gen Li - Department of Biochemistry, University of Iowa College of Medicine, Iowa City, Iowa, USA
Scott D Niles - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Christopher A Caldarone - Division of Cardiothoracic Surgery, University of Iowa College of Medicine, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: The Journal of thoracic and cardiovascular surgery, Vol.127(2), pp.490-497
Publisher: Mosby, Inc
DOI: 10.1016/j.jtcvs.2003.07.052
PMID: 14762359
ISSN: 0022-5223
eISSN: 1097-685X
Language: English
Date published: 2004
Academic Unit: Cardiology; Stead Family Department of Pediatrics; Surgery; Child and Community Health; Cardiothoracic Surgery
Record Identifier: 9984093362802771

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