High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death

Niederberger, Petra; Farine, Emilie; Arnold, Marlène; Wyss, Rahel K.; Sanz, María-Nieves; Méndez-Carmona, Natalia; Gahl, Brigitta; Fiedler, Georg Martin; Carrel, Thierry; Stahel, Hendrik T. Tevaearai; Longnus, Sarah L.

doi:10.1016/j.metabol.2017.03.007

Cited by 13 publications

(20 citation statements)

References 47 publications

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“…An isolated heart model of DCD heart transplantation was used, as previously reported [26,45,47,53,54], with male Wistar rats (Janvier Labs, Le Genest-Saint-Isle, France) of 10 to 11 weeks of age to ensure mature cardiac metabolism [55] and to represent young, adult human DCD donors. Rats were housed under standard conditions at a controlled room temperature with a 12-h light-dark cycle and access to water and food ad libitum.…”

Section: Isolated Heart Perfusionsmentioning

confidence: 99%

“…Buffer samples were taken at various reperfusion time points and stored at −20 • C until analyzed. Protocols for the measurement of glycolysis and glucose oxidation are described elsewhere [26,56]. Wet/dry weight ratio was used to normalize values.…”

Section: Rates Of Glycolysis and Glucose Oxidationmentioning

confidence: 99%

“…Cardiac oxygen efficiency was calculated as: Myocardial glycogen tissue content was determined using a spectrophotometric glucose assay kit (Sigma-Aldrich, St. Louis, MO, USA) as previously described [26,57]. Wet/dry weight ratio was used to normalize.…”

Section: Cardiac Oxygen Consumption and Oxygen Efficiencymentioning

confidence: 99%

“…Reperfusion of an ischemic area typically results in the rapid recovery of fatty acid oxidation, which inhibits glucose use, particularly its oxidation [24]. Importantly, in DCD, as well as in other clinical situations of warm ischemia-reperfusion, the heart is exposed to high levels of free fatty acids prior to warm ischemia [25], which can be detrimental for post-ischemic function [26]. Shifting energy substrate metabolism away from fatty acid oxidation and towards glucose use during early reperfusion has been proposed to limit IRI and improve subsequent contractile recovery [27].…”

Section: Introductionmentioning

confidence: 99%

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Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

Arnold

Méndez-Carmona

Gulac

et al. 2020

IJMS

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Donation after circulatory death (DCD) could improve donor heart availability; however, warm ischemia-reperfusion injury raises concerns about graft quality. Mechanical postconditioning (MPC) may limit injury, but mechanisms remain incompletely characterized. Therefore, we investigated the roles of glucose metabolism and key signaling molecules in MPC using an isolated rat heart model of DCD. Hearts underwent 20 min perfusion, 30 min global ischemia, and 60 minu reperfusion with or without MPC (two cycles: 30 s reperfusion—30 s ischemia). Despite identical perfusion conditions, MPC either significantly decreased (low recovery = LoR; 32 ± 5%; p < 0.05), or increased (high recovery = HiR; 59 ± 7%; p < 0.05) the recovery of left ventricular work compared with no MPC (47 ± 9%). Glucose uptake and glycolysis were increased in HiR vs. LoR hearts (p < 0.05), but glucose oxidation was unchanged. Furthermore, in HiR vs. LoR hearts, phosphorylation of raptor, a downstream target of AMPK, increased (p < 0.05), cytochrome c release (p < 0.05) decreased, and TNFα content tended to decrease. Increased glucose uptake and glycolysis, lower mitochondrial damage, and a trend towards decreased pro-inflammatory cytokines occurred specifically in HiR vs. LoR MPC hearts, which may result from greater AMPK activation. Thus, we identify endogenous cellular mechanisms that occur specifically with cardioprotective MPC, which could be elicited in the development of effective reperfusion strategies for DCD cardiac grafts.

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Section: Isolated Heart Perfusionsmentioning

confidence: 99%

Section: Rates Of Glycolysis and Glucose Oxidationmentioning

confidence: 99%

Section: Cardiac Oxygen Consumption and Oxygen Efficiencymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

Arnold

Méndez-Carmona

Gulac

et al. 2020

IJMS

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“…ATP levels. Tissue ATP levels were determined spectrophotometrically as previously described (Niederberger et al, 2017). Briefly, frozen ventricular tissue was powdered, resuspended in perchloric acid (7%), homogenized in a Dounce homogenizer and neutralized with KOH-KHCO 3 (1 mol/l).…”

Section: Animalsmentioning

confidence: 99%

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts

et al. 2020

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Olanzapine is an antipsychotic drug routinely used for the treatment of schizophrenia. Although the olanzapine treatment is associated with disturbed electrical heart activity, the exact mechanism underlying this severe adverse effect remains unclear. Recently, olanzapine administration was demonstrated to be associated with elevation of blood glucose and lower levels of free fatty acids. Therefore, we investigated the effect of acute olanzapine administration on pathways regulating the cardiac energy metabolism in an isolated heart. Electrical activity and contractile parameters were recorded in isolated, spontaneously beating, adult male rat hearts, perfused with either olanzapine (100 nmol/l) or the vehicle for 10 min. Regulation of key signalling molecules was evaluated by immunoblotting and ATP levels were measured spectrophotometrically. Olanzapine prolonged the QTc intervals and induced a higher number of premature ventricular beats. Furthermore, olanzapine significantly decreased the coronary flow, the rate-pressure product and the contractility (+dP/dt and –dP/dt). These changes were associated with an increased acetyl-CoA carboxylase phosphorylation and tissue ATP levels. We also found a trend for lower phosphorylation levels of Akt and its downstream products AS160, a key regulator of GLUT4 trafficking and glycogen synthase kinase‑3ß in olanzapine‑treated hearts when compared to vehicle-treated controls. These data should contribute to the elucidation of mechanisms that underlie the adverse cardiac effects of olanzapine.

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Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death

Méndez-Carmona

Wyss

Arnold

et al. 2019

The Journal of Heart and Lung Transplantation

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High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death

Cited by 13 publications

References 47 publications

Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts

Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death

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