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Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury.
Cardiovasc Res. 2013 Feb 01; 97(2):251-61.CR

Abstract

AIMS

Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium.

METHODS AND RESULTS

Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery.

CONCLUSIONS

Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores.

Authors+Show Affiliations

Cardiovascular Research Centre, University of Alberta, Edmonton, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23097573

Citation

Lou, Phing-How, et al. "Infarct-remodelled Hearts With Limited Oxidative Capacity Boost Fatty Acid Oxidation After Conditioning Against Ischaemia/reperfusion Injury." Cardiovascular Research, vol. 97, no. 2, 2013, pp. 251-61.
Lou PH, Zhang L, Lucchinetti E, et al. Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury. Cardiovasc Res. 2013;97(2):251-61.
Lou, P. H., Zhang, L., Lucchinetti, E., Heck, M., Affolter, A., Gandhi, M., Kienesberger, P. C., Hersberger, M., Clanachan, A. S., & Zaugg, M. (2013). Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury. Cardiovascular Research, 97(2), 251-61. https://doi.org/10.1093/cvr/cvs323
Lou PH, et al. Infarct-remodelled Hearts With Limited Oxidative Capacity Boost Fatty Acid Oxidation After Conditioning Against Ischaemia/reperfusion Injury. Cardiovasc Res. 2013 Feb 1;97(2):251-61. PubMed PMID: 23097573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury. AU - Lou,Phing-How, AU - Zhang,Liyan, AU - Lucchinetti,Eliana, AU - Heck,Markus, AU - Affolter,Andreas, AU - Gandhi,Manoj, AU - Kienesberger,Petra C, AU - Hersberger,Martin, AU - Clanachan,Alexander S, AU - Zaugg,Michael, Y1 - 2012/10/24/ PY - 2012/10/26/entrez PY - 2012/10/26/pubmed PY - 2013/8/3/medline SP - 251 EP - 61 JF - Cardiovascular research JO - Cardiovasc Res VL - 97 IS - 2 N2 - AIMS: Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium. METHODS AND RESULTS: Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery. CONCLUSIONS: Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores. SN - 1755-3245 UR - https://www.unboundmedicine.com/medline/citation/23097573/Infarct_remodelled_hearts_with_limited_oxidative_capacity_boost_fatty_acid_oxidation_after_conditioning_against_ischaemia/reperfusion_injury_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvs323 DB - PRIME DP - Unbound Medicine ER -