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Myocardial apoptosis after cardioplegic arrest in the neonatal lamb. J Thorac Cardiovasc Surg 2003 Jun;125(6):1268-75

Date

06/28/2003

Pubmed ID

12830043

DOI

10.1016/s0022-5223(02)73238-8

Scopus ID

2-s2.0-0037973476   14 Citations

Abstract

OBJECTIVE: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.

Author List

Hammel JM, Caldarone CA, Van Natta TL, Wang LX, Welke KF, Li W, Niles S, Barner E, Scholz TD, Behrendt DM, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Apoptosis
Blotting, Western
Caspases
Heart Arrest, Induced
In Situ Nick-End Labeling
Myocardium
Protein Array Analysis
RNA, Messenger
Sheep
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00