Premium
Decrease in fatty acid oxidation increases tolerance of the ageing heart to ischaemic injury
Author(s) -
Seymour AnneMarie L,
Sample Jessica,
Cleland John GF
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/fasebj.20.4.a739
Subject(s) - ageing , medicine , ischemia , cardiology , heart failure , hibernating myocardium , beta oxidation , myocardial infarction , endocrinology , metabolism , revascularization
Ageing is associated with reduced tolerance to myocardial infarction. Alterations in mitochondrial oxidative metabolism are important determinants in the contractile recovery of the adult heart after ischaemia. However, the profile of substrate metabolism during reperfusion in the ageing heart is unknown. The aim of this study was to investigate energy substrate preference and functional recovery following low flow ischaemia in the ageing heart. Hearts from 6 and 24 mo male Wistar rats were perfused in an isovolumic mode with buffer containing 3% albumin and a physiological mixture of substrates including 0.3mM [U‐ 13 C] palmitate, 1mM [3‐ 13 C] lactate and 5mM glucose. Cardiac work was increased by dobutamine infusion for 20 min (2.8±0.1 μg/min/g heart weight) followed by 30 min low flow ischaemia and 30 min reperfusion. Ischaemia caused similar reductions in left ventricular developed pressure and cardiac work in adult and senescent hearts. On reperfusion, 24 mo hearts demonstrated improved functional recovery relative to 6‐mo hearts. This was associated with a significant decline in palmitate oxidation and increase in lactate oxidation. Thus, the ageing heart has increased tolerance to severe ischaemia, which may be attributed to the reduction in fatty acid oxidation. JS is funded by a PhD scholarship from the University of Hull and Academic Dept of Cardiology.