title: Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.
abstract: Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, 1161 21st Avenue South, T4202 MCN, Nashville, TN, 37232, USA.|Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Salzman
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deklotz
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Gurpreet K
authors.initials: GK
authors.lastname: Dulai
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, 1161 21st Avenue South, T4202 MCN, Nashville, TN, 37232, USA.
authors.forename: Hunter F
authors.initials: HF
authors.lastname: Douglas
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, 1161 21st Avenue South, T4202 MCN, Nashville, TN, 37232, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Dikalova
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Weihrauch
authors.affiliation: Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Barnes
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, 1161 21st Avenue South, T4202 MCN, Nashville, TN, 37232, USA. matthias.riess@vanderbilt.edu.|Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA. matthias.riess@vanderbilt.edu.|TVHS VA Medical Center, Nashville, TN, USA. matthias.riess@vanderbilt.edu.
authors.forename: Matthias L
authors.identifier: http://orcid.org/0000-0001-8748-5757
authors.initials: ML
authors.lastname: Riess
mesh_terms: D000818:Animals; D004655:Emulsions / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010743:Phospholipids / Q000494:pharmacology*; D051381:Rats; D012589:Sciuridae; D012621:Seasons; D013024:Soybean Oil / Q000494:pharmacology*
chemical_list: D004655:Emulsions; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D005947:Glucose
keywords: Arctic ground squirrel; Brown Norway rat; Cardiac performance; Intralipid; Langendorff; Myocardial ischemia reperfusion injury