Short-term and long-term prognosis after cardiac surgery: Do anaesthetics protect against ischemia-reperfusion injury?

Liver transplantation has been identified as the most effective treatment for patients with end-stage liver diseases. However, hepatic ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post transplantation. Cell death, including apoptosis, necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft inflammation. The inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection, cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of cancer recurrence and fibrogenesis due to the long-term impact of inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.

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SIRT1-mediated acute cardioprotection

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00587.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. H1506-H1512 ◽

Cited By ~ 58

Author(s):

Sergiy M. Nadtochiy ◽

Hongwei Yao ◽

Michael W. McBurney ◽

Wei Gu ◽

Leonard Guarente ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Lysine Acetylation ◽

Short Term ◽

Lysine Deacetylase ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Overexpression studies have revealed a role for silent information regulator of transcription 1 (SIRT1) lysine deacetylase in cardioprotection against ischemia-reperfusion injury via long-term transcriptional effects. However, short-term SIRT1-mediated lysine deacetylation, within the context of acute cardioprotection, is poorly understood. In this study, the role of SIRT1 in the acute cardioprotective paradigm of first window ischemic preconditioning (IPC) was studied using SIRT1-deficient (SIRT1+/−) and SIRT1-overexpressing (SIRT1+++) mice. In wild-type hearts, cytosolic lysine deacetylation was observed during IPC, and overacetylation was observed upon pharmacological SIRT1 inhibition. Consistent with a role for SIRT1 in IPC, SIRT1+/− hearts could not be preconditioned and exhibited increased cytosolic lysine acetylation. Furthermore, SIRT1+++ hearts were endogenously protected against ischemia-reperfusion injury and exhibited decreased cytosolic acetylation. Both of these effects in SIRT1+++ mice were reversed by pharmacological SIRT1 inhibition on an acute timescale. Several downstream targets of SIRT1 were examined, with data suggesting possible roles for endothelial nitric oxide synthase phosphorylation, NF-κB, and stimulation of autophagy. In conclusion, these data suggest that SIRT1, acting on nontranscriptional targets, is required for cardioprotection by acute IPC and that SIRT1-dependent lysine deacetylation occurs during IPC and may play a role in cardioprotective signaling.

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Short-term immunosuppressive treatment of the donor ameliorates consequences of ischemia/ reperfusion injury and long-term graft function in renal allografts from older donors1

Transplantation Journal ◽

10.1097/01.tp.0000063408.97289.89 ◽

2003 ◽

Vol 75 (11) ◽

pp. 1786-1792 ◽

Cited By ~ 22

Author(s):

Anja Reutzel-Selke ◽

Thomas Zschockelt ◽

Christian Denecke ◽

Ulrike Bachmann ◽

Anke Jurisch ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Immunosuppressive Treatment ◽

Graft Function ◽

Short Term ◽

Renal Allografts

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Protection against myocardial ischemia/reperfusion injury by short-term diabetes: enhancement of VEGF formation, capillary density, and activation of cell survival signaling

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-006-0102-1 ◽

2006 ◽

Vol 373 (6) ◽

pp. 415-427 ◽

Cited By ~ 46

Author(s):

Guochuan Ma ◽

Mohamed Al-Shabrawey ◽

John A. Johnson ◽

Rahul Datar ◽

Huda E. Tawfik ◽

...

Keyword(s):

Myocardial Ischemia ◽

Cell Survival ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Capillary Density ◽

Short Term ◽

Myocardial Ischemia Reperfusion Injury ◽

Survival Signaling ◽

Myocardial Ischemia Reperfusion

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Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00114.2018 ◽

2018 ◽

Vol 315 (1) ◽

pp. H150-H158 ◽

Cited By ~ 16

Author(s):

Marie Hauerslev ◽

Sivagowry Rasalingam Mørk ◽

Kasper Pryds ◽

Hussain Contractor ◽

Jan Hansen ◽

...

Keyword(s):

Endothelial Function ◽

Glyceryl Trinitrate ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Rat Myocardium ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

Human Endothelium

Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

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