Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death—consequences of ischemic duration

2019 ◽  
Vol 38 (6) ◽  
pp. 647-657 ◽  
Author(s):  
Rahel K. Wyss ◽  
Natalia Méndez-Carmona ◽  
Maria-Nieves Sanz ◽  
Maria Arnold ◽  
Adrian Segiser ◽  
...  
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Early Reperfusion ◽  
Mitochondrial Integrity ◽  
Circulatory Death ◽  
Ischemic Duration ◽  
Isolated Rat

scholarly journals Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD)

2021 ◽  
Vol 8 ◽  
Author(s):  
Maria Arnold ◽  
Adrian Segiser ◽  
Selianne Graf ◽  
Natalia Méndez-Carmona ◽  
Maria N. Sanz ◽  
...  
Keyword(s):  
Rat Heart ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Mitochondrial Calcium ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Early Reperfusion ◽  
Lactate Levels ◽  
Circulatory Death ◽  
Isolated Rat

Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD.Methods: Isolated, working rat hearts underwent 28.5′ of global ischemia and 60′ of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360).Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac).Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts.

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

Metabolism ◽  
2017 ◽  
Vol 71 ◽  
pp. 107-117 ◽  
Author(s):  
Petra Niederberger ◽  
Emilie Farine ◽  
Maria Arnold ◽  
Rahel K. Wyss ◽  
Maria N. Sanz ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Cardiac Recovery ◽  
Circulatory Death ◽  
Isolated Rat

scholarly journals Cardioprotective reperfusion strategies differentially affect mitochondria: Studies in an isolated rat heart model of donation after circulatory death (DCD)

2018 ◽  
Vol 19 (2) ◽  
pp. 331-344 ◽  
Author(s):  
Maria N. Sanz ◽  
Emilie Farine ◽  
Petra Niederberger ◽  
Natalia Méndez-Carmona ◽  
Rahel K. Wyss ◽  
...  
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Circulatory Death ◽  
Isolated Rat

Characterization of Endothelial Function Following Various Ischemic Durations in an Isolated Rat Heart Model of Donation After Circulatory Death

2017 ◽  
Vol 101 ◽  
pp. S53
Author(s):  
Natalia Méndez Carmona ◽  
Rahel K. Wyss ◽  
Maria Arnold ◽  
Hendrik T. Tevaearai Stahel ◽  
Thierry P. Carrel ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Circulatory Death ◽  
Isolated Rat

Molecular and Metabolic Mechanisms of Mechanical Mostconditioning in an Isolated Rat Heart Model of Donation after Circulatory Death

2017 ◽  
Vol 101 ◽  
pp. S52
Author(s):  
Maria Arnold ◽  
Natalia Méndez Carmona ◽  
Patrik Gulac ◽  
Rahel K. Wyss ◽  
Hendrik Tevaearai Stahel ◽  
...  
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Circulatory Death ◽  
Isolated Rat

scholarly journals 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

2020 ◽  
Vol 21 (3) ◽  
pp. 964 ◽  
Author(s):  
Maria Arnold ◽  
Natalia Méndez-Carmona ◽  
Patrik Gulac ◽  
Rahel K Wyss ◽  
Nina Rutishauser ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Donation After Circulatory Death ◽  
Heart Model ◽  
Circulatory Death ◽  
Isolated Rat

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.

Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart?

2003 ◽  
Vol 285 (1) ◽  
pp. H316-H324 ◽  
Author(s):  
Richard Southworth ◽  
Pamela B. Garlick
Keyword(s):  
Rat Heart ◽  
Recovery Of Function ◽  
Electron Microscopic Examination ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Low Flow ◽  
Hibernating Myocardium ◽  
Heart Model ◽  
Electron Microscopic ◽  
Isolated Rat

The clinical hallmarks of hibernating myocardium include hypocontractility while retaining an inotropic reserve (using dobutamine echocardiography), having normal or increased [18F]fluoro-2-deoxyglucose-6-phosphate (18FDG6P) accumulation associated with decreased coronary flow [flow-metabolism mismatch by positron emission tomography (PET)], and recovering completely postrevascularization. In this study, we investigated an isolated rat heart model of hibernation using experimental equivalents of these clinical techniques. Rat hearts ( n = 5 hearts/group) were perfused with Krebs-Henseleit buffer for 40 min at 100% flow and 3 h at 10% flow and reperfused at 100% flow for 30 min (paced at 300 beats/min throughout). Left ventricular developed pressure fell to 30 ± 8% during 10% flow and recovered to 90 ± 7% after reperfusion. In an additional group, this recovery of function was found to be preserved over 2 h of reperfusion. Electron microscopic examination of hearts fixed at the end of the hibernation period demonstrated a lack of ischemic injury and an accumulation of glycogen granules, a phenomenon observed clinically. In a further group, hearts were challenged with dobutamine during the low-flow period. Hearts demonstrated an inotropic reserve at the expense of increased lactate leakage, with no appreciable creatine kinase release. PET studies used the same basic protocol in both dual- and globally perfused hearts (with 250MBq18FDG in Krebs buffer ± 0.4 mmol/l oleate). PET data showed flow-metabolism “mismatch;” whether regional or global,18FDG6P accumulation in ischemic tissue was the same as (glucose only) or significantly higher than (glucose + oleate) control tissue (0.023 ± 0.002 vs. 0.011 ± 0.002 normalized counts · s-1· g-1· min-1, P < 0.05) despite receiving 10% of the flow. This isolated rat heart model of acute hibernation exhibits many of the same characteristics demonstrated clinically in hibernating myocardium.

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