scholarly journals EPOR2/βcR2-independendent effects of low-dose epoetin-α in porcine liver transplantation

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Linus Kebschull ◽  
Leon Franz Christoph Theilmann ◽  
Annika Mohr ◽  
Wencke Uennigmann ◽  
Sandra Stoeppeler ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Low Dose ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Porcine Liver ◽  
Ischemic Time ◽  
Apoptotic Effects ◽  
Endothelial Nitric Oxide ◽  
Porcine Liver Transplantation

Ischemia–reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/βcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2/βcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/βcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model. Landrace pigs underwent allogenic liver transplantation (follow-up: 6 h) with a portojugular shunt. Animals were divided into two groups: donor and recipient treatment with low-dose EPO (65 IU/kg) or vehicle, administered 6 h before cold perfusion and 30 min after warm reperfusion. Fourteen of 17 animals (82.4%) fulfilled the inclusion criteria. No differences were noted in operative values between the groups including hemoglobin, cold or warm ischemic time. EPO-treated animals showed a significantly lower histopathology score, reduced apoptosis, oxidative stress, and most important a significant up-regulation of endothelial nitric oxide (NO) synthase (eNOS). Donor and recipient treatment with low-dose EPO reduces the hepatic IRI via EPOR2/βcR2-independent cytoprotective mechanisms and represents a clinically applicable way to reduce IRI.

scholarly journals Sequence of reperfusion influences ischemia/reperfusion injury and primary graft function following porcine liver transplantation

2005 ◽  
Vol 11 (10) ◽  
pp. 1214-1222 ◽  
Author(s):  
Jens G. Brockmann ◽  
Christian August ◽  
Heiner H. Wolters ◽  
Ralf Hömme ◽  
Daniel Palmes ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Porcine Liver ◽  
Porcine Liver Transplantation

scholarly journals The freeze-dried extracts of Salvia coccinea Juss. Ex Murray attenuate myocardial ischemia reperfusion injury in a global ischemia Rat model

2018 ◽  
Author(s):  
Nelly Murugi Nyaga ◽  
Peter Waweru Mwangi ◽  
Frederick Bukachi
Keyword(s):  
Reperfusion Injury ◽  
Low Dose ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Negative Control ◽  
Global Ischemia ◽  
High Dose ◽  
Protective Effects ◽  
Freeze Dried ◽  
Medium Dose

AbstractBackgroundIschemia reperfusion injury is the leading cause of myocardial cell death in Ischemic Heart Disease. Thus intensive research efforts are geared at discovering pharmacological approaches that prevent it. Over twenty species from the genus Salvia are widely applied in traditional Chinese medicine in the management of heart diseases with Salvia miltiorrhiza (Danshen) being a canonical example. Our study aimed to investigate the cardio-protective effects of the freeze-dried extracts of salvia coccinea against ischemia reperfusion injury in a rodent in-vitro model of global ischemia.MethodsForty two (42) Sprague Dawley rats were randomly assigned into five groups: positive control (Glucosamine 1000mg/kg), negative control group (Krebs Henseleit buffer), low dose test (50 mg/100ml), medium dose test (100 mg/100ml), and high dose test (200 mg/100ml).The cardio-protective effects of the different treatments were evaluated in a global ischemia model using isolated rat hearts mounted on a Langendorff system.Naloxone 2.2 μmol/L (μ opioid receptor blocker), and theophylline 1000 μmol/L (non-specific adenosine receptor blocker) were co-administered with 50 mg of S.coccinea in the mechanism of action experiments.The following indices of cardiac function were recorded pre- and post-ischemia: left ventricular developed pressure (LVDP), heart rate, and maximum rate of contraction and relaxation. All data were expressed as Mean ± Standard Error of Mean and analyzed using one-way ANOVA and Tukey post-hoc tests. Significance was set at p < 0.05.ResultsThe freeze-dried extracts of S. coccinea had significant effects on post-ischemic contractile function recovery in the early [51.4 ± 9.7% (low dose test) vs. 14.9 ± 3.3% (medium dose test) vs. 12.7 ± 2.6% (high dose test) vs. 13.7 ± 5.7% (negative control): p<0.05] and late [38.6 ± 8.9% (low dose test) vs. 22.0± 7.1% (medium dose test) vs. 14.6 ± 5.8 (high dose test) vs. 12.5 ± 4.2% (negative control): p< 0.05]. Reperfusion phases with the highest LVDP recovery were observed at the 50 mg dosage level.The freeze-dried extracts of S. coccinea had significant negative chronotropic effects on heart rate [234.0 ± 2.4 beats/min to 90.0 ± 7.0 beats/min, 50 mg vs. 102.0 ± 13.9 beats/min to 135.0 ± 25.9 beats/min, control P<0.05].The cardioprotective effects of S. coccinea displayed an inverted U-shaped dose-response curve with low dose stimulation and high dose inhibition.Naloxone completely abolished the LVDP recovery afforded by the freeze-dried extracts of S. coccinea at the 50 mg dosage level while adenosine only partly abolished the LVDP recovery (9.5 ± 3.2% (naloxone) vs. 15.5 ± 5.8% (adenosine): P>0.05).ConclusionThe freeze-dried extracts of S. coccinea possessed significant cardioprotective effects which appear to be mediated by activation of the opioidergic pathway in the heart.

Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination

2007 ◽  
Vol 293 (1) ◽  
pp. H813-H818 ◽  
Author(s):  
Yumei Ye ◽  
Yu Lin ◽  
Regino Perez-Polo ◽  
Ming-He Huang ◽  
Michael G. Hughes ◽  
...  
Keyword(s):  
Low Dose ◽  
Ischemia Reperfusion Injury ◽  
Synergistic Effects ◽  
Ischemia Reperfusion ◽  
Area At Risk ◽  
Phosphorylated Akt ◽  
High Doses ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Full Protection

Atorvastatin (ATV) limits infarct size (IS) by activating Akt and ecto-5-nucleotidase, which generates adenosine. Activated Akt and adenosine activate endothelial nitric oxide synthase (eNOS). When given orally, high doses (10 mg/kg) are needed to achieve full protection. We determined whether dipyridamole (DIP), by preventing the reuptake of adenosine, has a synergistic effect with ATV in reducing myocardial IS. In this study, rats received 3-days of the following: water, ATV (2 mg·kg−1·day−1), DIP (6 mg·kg−1·day−1), or ATV + DIP. In addition, rats received 3-days of the following: aminophylline (Ami; 10 mg·kg−1·day−1) or Ami + ATV + DIP. Rats underwent 30 min of myocardial ischemia followed by 4 h of reperfusion (IS protocol), or hearts were explanted for immunoblotting. As a result, IS in the controls was 34.0 ± 2.8% of the area at risk. ATV (33.1 ± 2.1%) and DIP (30.5 ± 1.5%) did not affect IS, whereas ATV + DIP reduced IS (12.2 ± 0.5%; P < 0.001 vs. each of the other groups). There was no difference in IS between the Ami alone (48.1 ± 0.8%) and the Ami + ATV + DIP (45.8 ± 2.9%) group ( P = 0.422), suggesting that Ami completely blocked the protective effect. Myocardial adenosine level in the controls was 30.6 ± 3.6 pg/μl. ATV (51.0 ± 4.9 pg/μl) and DIP (51.5 ± 6.8 pg/μl) caused a small increase in adenosine levels, whereas ATV + DIP caused a greater increase in adenosine levels (66.4 ± 3.1 pg/μl). ATV and DIP alone did not affect myocardial Ser473 phosphorylated-Akt and Ser1177 phosphorylated-eNOS levels, whereas ATV + DIP significantly increased them. In conclusion, low-dose ATV and DIP had synergistic effects in reducing myocardial IS and activation of Akt and eNOS. This combination may have a potential benefit in augmenting the eNOS-mediated pleiotropic effects of statins.

scholarly journals New Insights into the Liver–Visceral Adipose Axis During Hepatic Resection and Liver Transplantation

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1100
Author(s):  
María Eugenia Cornide-Petronio ◽  
Mónica B. Jiménez-Castro ◽  
Jordi Gracia-Sancho ◽  
Carmen Peralta
Keyword(s):  
Liver Transplantation ◽  
Adipose Tissue ◽  
Hepatic Resection ◽  
Visceral Adipose Tissue ◽  
Liver Surgery ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Visceral Adipose

In the last decade, adipose tissue has emerged as an endocrine organ with a key role in energy homeostasis. In addition, there is close crosstalk between the adipose tissue and the liver, since pro- and anti-inflammatory substances produced at the visceral adipose tissue level directly target the liver through the portal vein. During surgical procedures, including hepatic resection and liver transplantation, ischemia–reperfusion injury induces damage and regenerative failure. It has been suggested that adipose tissue is associated with both pathological or, on the contrary, with protective effects on damage and regenerative response after liver surgery. The present review aims to summarize the current knowledge on the crosstalk between the adipose tissue and the liver during liver surgery. Therapeutic strategies as well as the clinical and scientific controversies in this field are discussed. The different experimental models, such as lipectomy, to evaluate the role of adipose tissue in both steatotic and nonsteatotic livers undergoing surgery, are described. Such information may be useful for the establishment of protective strategies aimed at regulating the liver–visceral adipose tissue axis and improving the postoperative outcomes in clinical liver surgery.

Genetic overexpression of eNOS attenuates hepatic ischemia-reperfusion injury

2006 ◽  
Vol 291 (6) ◽  
pp. H2980-H2986 ◽  
Author(s):  
Mark R. Duranski ◽  
John W. Elrod ◽  
John W. Calvert ◽  
Nathan S. Bryan ◽  
Martin Feelisch ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Soluble Guanylyl Cyclase ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Wild Type ◽  
Hepatic Ischemia ◽  
No Signaling ◽  
Hepatic Ischemia Reperfusion ◽  
Endothelial Nitric Oxide

Previous studies have shown that endothelial nitric oxide (NO) synthase (eNOS)-derived NO is an important signaling molecule in ischemia-reperfusion (I-R) injury. Deficiency of eNOS-derived NO has been shown to exacerbate injury in hepatic and myocardial models of I-R. We hypothesized that transgenic overexpression of eNOS (eNOS-TG) would reduce hepatic I-R injury. We subjected two strains of eNOS-TG mice to 45 min of hepatic ischemia and 5 h of reperfusion. Both strains were protected from hepatic I-R injury compared with wild-type littermates. Because the mechanism for this protection is still unclear, additional studies were performed by using inhibitors and activators of both soluble guanylyl cyclase (sGC) and heme oxygenase-1 (HO-1) enzymes. Blocking sGC with 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) and HO-1 with zinc (III) deuteroporphyrin IX-2,4-bisethyleneglycol (ZnDPBG) in wild-type mice increased hepatic I-R injury, whereas pharmacologically activating these enzymes significantly attenuated I-R injury in wild-type mice. Interestingly, ODQ abolished the protective effects of eNOS overexpression, whereas ZnDPBG had no effect. These results suggest that hepatic protection in eNOS-TG mice may be mediated in part by NO signaling via the sGC-cGMP pathway and is independent of HO-1 signal transduction pathways.

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