Lou 2012 Cardiovasc Res
| Lou PH, Zhang L, Lucchinetti E, Heck M, Affolter A, Gandhi M, Kienesberger PC, Hersberger M, Clanachan AS, Zaugg M (2012) Infarct-remodeled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischemia/reperfusion injury. Cardiovasc Res 97:251-61. |
Lou PH, Zhang L, Lucchinetti E, Heck M, Affolter A, Gandhi M, Kienesberger PC, Hersberger M, Clanachan AS, Zaugg M (2012) Cardiovasc Res
Abstract: Aims: Infarct-remodeled hearts are less amenable to protection against ischemia-reperfusion. Understanding preservation of energy metabolism in diseased versus healthy hearts may help to develop anti-ischemic strategies also effective in jeopardized myocardium.
Methods and Results: Isolated infarct-remodeled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischemia and 30 min of reperfusion. Protection of postischemic ventricular work was achieved by pharmacologic 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 fibers. 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, hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodeling and limited respiratory chain and citric acid cycle capacity. Unprotected remodeled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischemia/reperfusion, which normalized in sevoflurane-protected remodeled hearts. Protected remodeled hearts also showed higher Ξ²-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibers and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodeled hearts exhibited higher PPARΞ±-PGC-1Ξ± but defective HIF-1Ξ± signaling and conditioning enabled them to mobilize fatty acids from endogenous triglyceride store, which closely correlated with improved recovery.
Conclusions: Protected infarct-remodeled hearts secure postischemic energy production by activation of Ξ²-oxidation and mobilization of fatty acids from endogenous triglyceride stores. β’ Keywords: Ξ²-oxidation, Infarct, Fatty acid oxidation
β’ O2k-Network Lab: CA Edmonton Zaugg M
Labels:
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue
Regulation: Substrate, Fatty acid Coupling state: OXPHOS Pathway: F, N, S, NS HRR: Oxygraph-2k
