Myocardial apoptosis after cardioplegic arrest in the neonatal lamb

James M Hammel; Christopher A Caldarone; Timothy L Van Natta; Li Xing Wang; Karl F Welke; Weigen Li; Scott Niles; Elisa Barner; Thomas D Scholz; Douglas M Behrendt; Jeffrey L Segar

doi:10.1016/S0022-5223(02)73238-8

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Myocardial apoptosis after cardioplegic arrest in the neonatal lamb

Journal article

Open access

Peer reviewed

Myocardial apoptosis after cardioplegic arrest in the neonatal lamb

James M Hammel, Christopher A Caldarone, Timothy L Van Natta, Li Xing Wang, Karl F Welke, Weigen Li, Scott Niles, Elisa Barner, Thomas D Scholz, Douglas M Behrendt, …

The Journal of thoracic and cardiovascular surgery, Vol.125(6), pp.1268-1273

06/2003

DOI: 10.1016/S0022-5223(02)73238-8

PMID: 12830043

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Abstract

Myocardial apoptosis is observed after various cardiac injuries and is also a normal part of fetal cardiac development and early postnatal maturation. Cardioplegic arrest and reperfusion result in ischemic injury and oxidative stress, known triggers of apoptosis. Because the neonatal heart is in a proapoptotic state, we hypothesize that apoptosis is triggered after cardioplegic arrest in neonatal myocardium. We started neonatal lambs (6-8 days old, n = 5) on cardiopulmonary bypass and administered cold crystalloid cardioplegia at 20-minute intervals. Total crossclamp time was 70 minutes, and bypass time was 90 minutes. After a six-hour recovery period, the hearts were excised and examined by using TdT-mediated dUTP nick-end labeling; radiolabeled DNA electrophoresis; fluorimetric caspase 3, 8, and 9 activity assay; mRNA microarray; and Western immunoblotting. Control lambs were anesthetized but did not undergo operation (n = 5) or were started on cardiopulmonary bypass for 90 minutes but not arrested (n = 5). Lambs subjected to cardioplegia had 5-fold more TdT-mediated dUTP nick-end labeling-positive nuclei compared with that seen in unoperated control animals (P =.007) and bypass-only control animals (P =.008). DNA laddering was present in all postcardioplegia hearts but absent among control hearts. Bad and Bcl-X mRNA transcription increased significantly. Caspase 3, 8, and 9 activities were slightly greater than those seen in control animals, but the differences were not significant. No change was detected in Bcl-2, Bax, or Bcl-xL proteins. In a clinically relevant model of neonatal cardioplegic arrest, increased apoptotic cell death is present 6 hours after reperfusion, and both proapoptotic and antiapoptotic responses are triggered. The clinical implications of apoptosis after cardioplegic arrest remain undetermined.

Animals, Newborn

Heart Arrest, Induced - adverse effects

In Situ Nick-End Labeling

Animals

Protein Array Analysis

RNA, Messenger - analysis

Myocardium - pathology

Sheep

Apoptosis - physiology

Caspases - analysis

Blotting, Western

Details

Title: Subtitle: Myocardial apoptosis after cardioplegic arrest in the neonatal lamb
Creators: James M Hammel - Department of Surgery, the University of Iowa College of Medicine, Iowa City, Iowa, USA
Christopher A Caldarone
Timothy L Van Natta
Li Xing Wang
Karl F Welke
Weigen Li
Scott Niles
Elisa Barner
Thomas D Scholz
Douglas M Behrendt
Jeffrey L Segar
Resource Type: Journal article
Publication Details: The Journal of thoracic and cardiovascular surgery, Vol.125(6), pp.1268-1273
DOI: 10.1016/S0022-5223(02)73238-8
PMID: 12830043
ISSN: 0022-5223
eISSN: 1097-685X
Grant note: R01HO64770 / NHLBI NIH HHS
Language: English
Date published: 06/2003
Academic Unit: Cardiology; Stead Family Department of Pediatrics; Surgery; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health
Record Identifier: 9984093457002771

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