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Reversal of mitochondrial defects before ischemia protects the aged heart
Author(s) -
Lesnefsky Edward J.,
He Dingchao,
Moghaddas Shadi,
Hoppel Charles L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4535fje
Subject(s) - ischemia , medicine , oxidative stress , lactate dehydrogenase , mitochondrion , cytochrome c oxidase , oxidative phosphorylation , reperfusion injury , endocrinology , cardiology , anesthesia , chemistry , biochemistry , enzyme
ABSTRACT Myocardial injury is increased in the aged heart during ischemia and reperfusion. Aging decreases oxidative metabolism in interfibrillar mitochondria (IFM) located between the myofibrils. We asked whether reversal of aging defects in IFM before ischemia would decrease injury in the aged heart following ischemia and reperfusion. Treatment with acetylcarnitine (AcCN) increases the activity of cytochrome oxidase in the aged heart. Aged (24 months) and adult (6 months) Fischer 344 rats were treated with AcCN (300 mg/kg i.p. 3 h before excision of the heart) or served as controls. AcCN restored oxidative phosphorylation and the activity of complexes III and IV in IFM from aged hearts to rates present in adults. Isolated hearts underwent 25 min global ischemia and 30 min reperfusion without additional treatment. Contractile recovery during reperfusion improved in hearts from AcCN‐treated aged rats compared to aged controls and were similar to adults in recovery. AcCN‐treated aged hearts sustained less damage, indicated by decreased lactate dehydrogenase (LDH) release during reperfusion. AcCN treatment did not alter functional recovery or LDH release in adults. Restoration of mitochondrial function in the aged heart before ischemia was accompanied by enhanced contractile recovery and decreased tissue injury following ischemia and reperfusion.— Lesnefsky, E. J., He, D., Moghaddas, S., Hoppel, C. L. Reversal of mitochondrial defects before ischemia protects the aged heart. FASEB J. 20, E840–E845 (2006)