INFLAMMATION, OXIDATIVE STRESS AND FUNCTIONAL DECLINE OF THE HEART DURING EX SITU HEART PERFUSION: ARE LEUKOCYTES THE ULTIMATE VILLAINS?

2020 ◽  
Vol 36 (10) ◽  
pp. S69
Author(s):  
S. Hatami ◽  
X. Qi ◽  
S. Bozso ◽  
M. Khan ◽  
B. Tkachuk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Functional Decline ◽  
Ex Situ ◽  
Heart Perfusion

OXIDATIVE STRESS AND RELATED RESPONSES ARE INDUCED DURING EX-SITU HEART PERFUSION AND MAY CONTRIBUTE TO THE FUNCTIONAL DECLINE OF THE EX-SITU-PERFUSED HEART

2019 ◽  
Vol 35 (10) ◽  
pp. S106
Author(s):  
S. Hatami ◽  
X. Qi ◽  
C. White ◽  
M. Buchko ◽  
S. Bozso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Functional Decline ◽  
Ex Situ ◽  
Perfused Heart ◽  
Heart Perfusion

scholarly journals A Novel Rat Model of Cardiac Donation After Circulatory Death Combined With Normothermic ex situ Heart Perfusion

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiale Li ◽  
Chuqing Xue ◽  
Xiao Ling ◽  
Yu Xie ◽  
Desai Pavan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Rat Model ◽  
Energy State ◽  
Ex Situ ◽  
Cell Swelling ◽  
Donation After Circulatory Death ◽  
Histopathological Changes ◽  
Heart Perfusion ◽  
Circulatory Death

Background: In heart transplantation, the adoption of hearts from donation after circulatory death (DCD) is considered to be a promising approach to expanding the donor pool. Normothermic ex situ heart perfusion (ESHP) is emerging as a novel preservation strategy for DCD hearts. Therefore, pre-clinical animal models of ESHP are essential to address some key issues before efficient clinical translation. We aim to develop a novel, reproducible, and economical rat model of DCD protocol combined with normothermic ESHP.Methods: Circulatory death of the anesthetized rats in the DCD group was declared when systolic blood pressure below 30 mmHg or asystole was observed after asphyxiation. Additional 15 min of standoff period was allowed to elapse. After perfusion of cold cardioplegia, the DCD hearts were excised and perfused with allogenic blood-based perfusate at constant flow for 90 min in the normothermic ESHP system. Functional assessment and blood gas analysis were performed every 30 min during ESHP. The alteration of DCD hearts submitted to different durations of ESHP (30, 60, and 90 min) in oxidative stress, apoptosis, tissue energy state, inflammatory response, histopathology, cell swelling, and myocardial infarction during ESHP was evaluated. Rats in the non-DCD group were treated similarly but not exposed to warm ischemia and preserved by the normothermic ESHP system for 90 min.Results: The DCD hearts showed compromised function at the beginning of ESHP and recovered over time, while non-DCD hearts presented better cardiac function during ESHP. The alteration of DCD hearts in oxidative stress, apoptosis, tissue energy state, histopathological changes, cell swelling, and inflammatory response didn't differ among different durations of ESHP. At the end of 90-min ESHP, DCD, and non-DCD hearts presented similarly in apoptosis, oxidative stress, inflammatory response, myocardial infarction, and histopathological changes. Moreover, the DCD hearts had lower energy storage and more evident cell swelling compared to the non-DCD hearts.Conclusion: We established a reproducible, clinically relevant, and economical rat model of DCD protocol combined with normothermic ESHP, where the DCD hearts can maintain a stable state during 90-min ESHP.

scholarly journals Myocardial Functional Decline During Prolonged Ex Situ Heart Perfusion

2019 ◽  
Vol 108 (2) ◽  
pp. 499-507 ◽  
Author(s):  
Sanaz Hatami ◽  
Christopher W. White ◽  
Shubham Shan ◽  
Alois Haromy ◽  
Xiao Qi ◽  
...  
Keyword(s):  
Functional Decline ◽  
Ex Situ ◽  
Heart Perfusion

scholarly journals The Impact of Ex Situ Heart Perfusion in Pediatric Transplantation: An Analysis of the UNOS Registry

2021 ◽  
Vol 40 (4) ◽  
pp. S39
Author(s):  
J. Conway ◽  
Y. Hong ◽  
T. Pidborochynski ◽  
M. Khan ◽  
D.H. Freed
Keyword(s):  
Ex Situ ◽  
Pediatric Transplantation ◽  
Heart Perfusion ◽  
The Impact

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

Metabolic Alterations in Myocardial Metabolism during Ex Situ Heart Perfusion

2019 ◽  
Vol 38 (4) ◽  
pp. S237
Author(s):  
S. Hatami ◽  
C.W. White ◽  
X. Qi ◽  
M. Buchko ◽  
S. Himmat ◽  
...  
Keyword(s):  
Myocardial Metabolism ◽  
Ex Situ ◽  
Metabolic Alterations ◽  
Heart Perfusion

scholarly journals Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e45805 ◽  
Author(s):  
Yuichi Uchino ◽  
Tetsuya Kawakita ◽  
Masaki Miyazawa ◽  
Takamasa Ishii ◽  
Hiromi Onouchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Functional Decline ◽  
Tear Production

scholarly journals Echocardiographic Assessment of Left Ventricular Function in Ex Situ Heart Perfusion using Pump Supported and Passive Afterload Working Mode, a pilot study.

2020 ◽  
Author(s):  
Arnaud Romeo Mbadjeu Hondjeu ◽  
Azad Mashari ◽  
Ryan Ramos ◽  
Giulia Maria Ruggeri ◽  
Joshua Qua Hiansen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Ex Situ ◽  
Heart Perfusion ◽  
Echocardiographic Assessment ◽  
Mode A

scholarly journals Metabolic Effects of Doxorubicin on the Rat Liver Assessed With Hyperpolarized MRI and Metabolomics

2022 ◽  
Vol 12 ◽  
Author(s):  
Kerstin N. Timm ◽  
Vicky Ball ◽  
Jack J. Miller ◽  
Dragana Savic ◽  
James A. West ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbohydrate Metabolism ◽  
Liver Damage ◽  
Functional Decline ◽  
High Energy ◽  
Metabolic Effects ◽  
Resonance Spectroscopy ◽  
Acid Uptake ◽  
High Energy Phosphates ◽  
Time Point

Doxorubicin (DOX) is a successful chemotherapeutic widely used for the treatment of a range of cancers. However, DOX can have serious side-effects, with cardiotoxicity and hepatotoxicity being the most common events. Oxidative stress and changes in metabolism and bioenergetics are thought to be at the core of these toxicities. We have previously shown in a clinically-relevant rat model that a low DOX dose of 2 mg kg–1 week–1 for 6 weeks does not lead to cardiac functional decline or changes in cardiac carbohydrate metabolism, assessed with hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy (MRS). We now set out to assess whether there are any signs of liver damage or altered liver metabolism using this subclinical model. We found no increase in plasma alanine aminotransferase (ALT) activity, a measure of liver damage, following DOX treatment in rats at any time point. We also saw no changes in liver carbohydrate metabolism, using hyperpolarized [1-13C]pyruvate MRS. However, using metabolomic analysis of liver metabolite extracts at the final time point, we found an increase in most acyl-carnitine species as well as increases in high energy phosphates, citrate and markers of oxidative stress. This may indicate early signs of steatohepatitis, with increased and decompensated fatty acid uptake and oxidation, leading to oxidative stress.

P5381Lack of sirtuin 5 aggravates myocardial ischemia reperfusion injury

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C N Witt ◽  
C Koentges ◽  
K Pfeil ◽  
L Vogelbacher ◽  
T Pusdrowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Oxidative Stress ◽  
Heart Perfusion ◽  
Dependent Protein ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Developed Pressure

Abstract Sirtuin 5 (SIRT5) is a mitochondrial NAD+-dependent protein deacylase which regulates the enzymatic activity of numerous mitochondrial proteins due to increased succinylation and malonylation, including enzymes of energy substrate oxidation and mitochondrial antioxidant enzymes. Since energy depletion and mitochondrial oxidative stress contribute to myocardial IR injury, it was our objective to evaluate the potential role of SIRT5 in IR injury. In regular Langendorff heart perfusions, 8 week-old cardiomyocyte-selective SIRT5−/− mice showed no difference in LV developed pressure or dp/dt max compared to wildtype mice. However, recovery of LV developed pressure and dp/dt max following 25 min of ischemia was lower by 34% and 20% in SIRT5−/− mice compared to WT mice, respectively. In contrast, postischemic recovery of cardiac function was not impaired and even improved in mice with cardiomyocyte-selective overexpression of SIRT5 compared to WT mice undergoing IR. Mitochondrial H2O2 generation was significantly increased in SIRT5−/− mice compared to WT mice following IR, and mitochondria-targeted antioxidant treatments (MnTBAP or SS-31) during heart perfusion completely normalized recovery of contractile parameters in SIRT5−/− mice following IR. In conclusion, SIRT5 is not required to maintain cardiac function under physiological conditions. However, lack of SIRT5 aggravates myocardial IR injury, likely by increasing mitochondrial oxidative stress. SIRT5 agonism may thus represent a potential therapeutic strategy to attenuate myocardial IR injury.

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