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Neonatal vulnerability to ischemia and reperfusion: Cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs.
- Source :
-
The Journal of thoracic and cardiovascular surgery [J Thorac Cardiovasc Surg] 2004 Feb; Vol. 127 (2), pp. 490-7. - Publication Year :
- 2004
-
Abstract
- Objectives: 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.<br />Methods: 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.<br />Results: 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).<br />Conclusions: 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.
- Subjects :
- Animals
Apoptosis physiology
Blotting, Western
Caspases metabolism
Cytochrome c Group metabolism
Disease Models, Animal
Electron Transport Complex IV metabolism
Enzyme Activation physiology
Fluorescent Dyes
Heart Arrest, Induced adverse effects
Heart Ventricles pathology
In Situ Nick-End Labeling
Indoles
MAP Kinase Kinase Kinase 5
MAP Kinase Kinase Kinases metabolism
Models, Cardiovascular
Myocardial Reperfusion Injury physiopathology
Myocardium cytology
Myocardium metabolism
Myocardium pathology
Myocytes, Cardiac metabolism
Oxidative Stress physiology
Proto-Oncogene Proteins metabolism
Sheep
Animals, Newborn physiology
Myocardial Reperfusion Injury etiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-5223
- Volume :
- 127
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of thoracic and cardiovascular surgery
- Publication Type :
- Academic Journal
- Accession number :
- 14762359
- Full Text :
- https://doi.org/10.1016/j.jtcvs.2003.07.052