Original Article| Volume 186, P36-51.e2, August 2017

Postconditioning with Intralipid emulsion protects against reperfusion injury in post-infarct remodeled rat hearts by activation of ROS-Akt/Erk signaling

      The clinically used lipid emulsion Intralipid (ILE) reduces ischemia reperfusion injury in healthy rodent hearts. We tested whether ILE is cardioprotective in postinfarct remodeled hearts. Post-infarct remodeled and sham Sprague-Dawley rat hearts were perfused in working mode and subjected to ischemia (15 minutes) and reperfusion (30 minutes). Left ventricular (LV) work was measured in hearts that were untreated or that received ILE (1%) postconditioning administered at the onset of reperfusion, or the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine (10 μM) alone or in combination with ILE. Mitochondrial O2 consumption was measured in LV muscle fibers. Acetyl CoA production was calculated from the oxidation of [U-14C]glucose and [9,10-3H]palmitate. ROS production was assessed by loss of aconitase activity as well as by release of hydrogen peroxide. Phosphorylation of Akt, Erk1/2, and STAT3 were used to evaluate protection signaling. Remodeled hearts exhibited LV dysfunction and signs of hypertrophy consistent with significant postinfarct remodeling. ILE postconditioning enhanced the recovery of postischemic LV function in remodeled hearts, preserved energy metabolism in mitochondria, accelerated palmitate oxidation and acetyl CoA production, and activated Akt/Erk/STAT3 in a ROS-dependent manner. Protection by ILE postconditioning evolved rapidly within the first minutes of reperfusion without evidence of additional cardiotonic effects due to provision of supplementary energy substrates potentially released from ILE during reperfusion. ILE represents a novel and clinically feasible cardioprotective strategy that is highly effective in remodeled hearts. Our data provide a rationale for the clinical evaluation of ILE postconditioning where ILE is administered as a bolus at the onset of reperfusion.


      ADP (adenosine diphosphate), Akt (protein kinase B), ANOVA (analysis of variance), ANP (atrial natriuretic peptide), ATP (adenosine triphosphate), BSA (bovine serum albumin), CAL (coronary artery ligation), COX (cytochrome c oxidase), CS (citrate synthase), DTNB (5,5′-dithiobis-(2-nitrobenzoic acid)), ECL (enhanced chemiluminescence), EF (left ventricular ejection fraction), EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid), Erk (extracellular signal–regulated kinase), ETC (electron transport chain), FS (left ventricular fractional shortening), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), HRP (horseradish peroxidase), Hz (hertz), ILE (Intralipid emulsion), IR (ischemia reperfusion), LV (left ventricular), LVEDD (left ventricular end-diastolic diameter), LVESD (left ventricular end-systolic diameter), MPG (N-(2-mercaptopropionyl)glycine), mPTP (mitochondrial permeability transition pore), NADP (nicotinamide adenine dinucleotide phosphate), NHE (sodium-hydrogen exchanger), NP-40 (nonyl phenoxypolyethoxylethanol), PAGE (polyacrylamide gel electrophoresis), RISK (reperfusion injury salvage kinase), ROS (reactive oxygen species), SDS (sodium dodecyl sulfate), SEM (standard error of mean), SOD (superoxide dismutase), STAT3 (signal transducer and activator of transcription 3), Tris-HCl (2-amino-2-(hydroxymethyl)-1,3-propanediol hydrochloride)
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