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.

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.

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.

Accelerated BMIPP uptake immediately after reperfused ischemia in the isolated rat heart model

2011 ◽  
Vol 25 (8) ◽  
pp. 560-565
Author(s):  
Kenji Fukushima ◽  
Mitsuru Momose ◽  
Chisato Kondo ◽  
Nobuhisa Hagiwara ◽  
Shuji Sakai
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Heart Model ◽  
Bmipp Uptake ◽  
Isolated Rat

scholarly journals Dose-dependent Effects of Perfluorocarbon Based Blood Substitute Perftoran on Cardyodinamics in Animal Model of Ischemia-reperfusion Injury

2021 ◽  
Author(s):  
Vladimir Jakovljevic ◽  
Sergey Vorobyev ◽  
Sergey Bolevich ◽  
Elena Morozova ◽  
Stefani Bolevich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Reperfusion Injury ◽  
Rat Heart ◽  
Ex Vivo ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Isolated Rat

Abstract The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values ​​of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.

Hyperbaric oxygen worsens myocardial low flow ischemia-reperfusion injury in isolated rat heart

1997 ◽  
Vol 320 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Sonia Radice ◽  
Giuseppe Rossoni ◽  
Giorgio Oriani ◽  
Michael Michael ◽  
Enzo Chiesara ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Hyperbaric Oxygen ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Low Flow ◽  
Isolated Rat

Detection of Cardiac Variability in the Isolated Rat Heart

2006 ◽  
Vol 8 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Autumn M. Schumacher ◽  
Joseph P. Zbilut ◽  
Charles L. Webber ◽  
Dorie W. Schwertz ◽  
Mariann R. Piano
Keyword(s):  
Rat Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Rat Hearts ◽  
Before And After ◽  
Quantification Analysis ◽  
Physical Attributes ◽  
Cardiac Variability ◽  
Isolated Rat

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart—a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

ATP-loaded immunoliposomes specific for cardiac myosin provide improved protection of the mechanical functions of myocardium from global ischemia in an isolated rat heart model

2006 ◽  
Vol 14 (5) ◽  
pp. 273-280 ◽  
Author(s):  
Daya D. Verma ◽  
Tatyana S. Levchenko ◽  
Eugene A. Bernstein ◽  
Dmitriy Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Global Ischemia ◽  
Cardiac Myosin ◽  
Heart Model ◽  
Isolated Rat
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