scholarly journals Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through α2-Adrenergic Receptor/AMPK-Dependent Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Xiao ◽  
Junpeng Li ◽  
Lisheng Qiu ◽  
Chuan Jiang ◽  
Yanhui Huang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Adrenergic Receptor ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Human Cardiomyocytes ◽  
Cellular Models ◽  
Ventricular Tissue

Background: Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist Dexmedetomidine (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown.Methods and Results: Human ventricular tissue from tetralogy of Fallot (TOF) patients and CMs derived from human-induced pluripotent stem cells (iPSC-CMs) were used to assess whether and how Dex protects human CMs from I/R. The results showed that when pretreated with Dex, the apoptosis marker-TUNEL and cleaved caspase 3 in the ventricular tissue were significantly reduced. In addition, the autophagy marker LC3II was significantly increased compared with that of the control group. When exposed to the hypoxia/reoxygenation process, iPSC-CMs pretreated with Dex also showed reduced TUNEL and cleaved caspase 3 and increased LC3II. When the autophagy inhibitor (3-methyladenine, 3-MA) was applied to the iPSC-CMs, the protective effect of Dex on the CMs was largely blocked. In addition, when the fusion of autophagosomes with lysosomes was blocked by Bafilomycin A1, the degradation of p62 induced by Dex during the autophagy process was suspended. Moreover, when pretreated with Dex, both the human ventricle and the iPSC-CMs expressed more AMP-activated protein kinase (AMPK) and phospho AMPK (pAMPK) during the I/R process. After AMPK knockout or the use of an α2-adrenergic receptor antagonist-yohimbine, the protection of Dex and its enhancement of autophagy were inhibited.Conclusion: Dex protects young human CMs from I/R injury, and α2-adrenergic receptor/AMPK-dependent autophagy plays an important role during this process. Dex may have a therapeutic effect for children with CHD who undergo long-term cardiac surgical processes.

Effects of Hydrogen-rich Water on the PI3K/AKT Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury

2020 ◽  
Vol 20 (5) ◽  
pp. 396-406 ◽  
Author(s):  
Liangtong Li ◽  
Xiangzi Li ◽  
Zhe Zhang ◽  
Li Liu ◽  
Tongtong Liu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
Water Group

Background: The effects of hydrogen-rich water on PI3K/AKT-mediated apoptosis were studied in rats subjected to myocardial ischemia-reperfusion injury (MIRI). Methdos: Sixty rats were divided randomly into a hydrogen-rich water group and a control group. The hearts were removed and fixed in a Langendorff device. Hearts from the control group were perfused with K-R solution, and hearts from the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The two treatment groups were then divided randomly into pre-ischemic period, ischemic period and reperfusion period groups(10 rats per group), which were subjected to reverse perfusion for 10 min, normal treatment for 20 min, and reperfusion for 20 min, respectively. The mRNA and protein expression levels of PI3K, AKT, p-AKT, FoxO1, Bim and Caspase-3 in each group were detected by RT-qPCR, immunohistochemistry (IHC) and Western blotting. Caspase-3 activity was detected by spectrophotometry. Results: Among the hydrogen-rich water group, the PI3K/AKT signaling pathway was significantly activated, and FoxO1, Bim, and Caspase-3 mRNA and protein levels were significantly decreased in ischemia-reperfusion subgroup compared with the preischemic and ischemic subgroups. In the ischemia-reperfusion hydrogen-rich water group, PI3K, AKT and p-AKT mRNA and protein expression levels were increased while the FoxO1, Bim and Caspase-3 expression levels were significantly decreased compared with those in the corresponding control group (p<0.05). Conclusion: Hydrogen-rich water can activate the PI3K/AKT signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts, and inhibit cardiomyocyte apoptosis.

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury

2004 ◽  
Vol 286 (5) ◽  
pp. H1923-H1935 ◽  
Author(s):  
James D. McCully ◽  
Hidetaka Wakiyama ◽  
Yng-Ju Hsieh ◽  
Mara Jones ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Parp Cleavage ◽  
Control Group ◽  
Early Reperfusion

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts ( n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately ( n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased ( P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased ( P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis ( P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

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

2018 ◽  
Vol 315 (1) ◽  
pp. H150-H158 ◽  
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.

scholarly journals Surfactant pretreatment decreases long-term damage after ischemia-reperfusion injury of the lung☆

2009 ◽  
Vol 35 (2) ◽  
pp. 304-312 ◽  
Author(s):  
Niels P. van der Kaaij ◽  
Jolanda Kluin ◽  
Jack J. Haitsma ◽  
Michael A. den Bakker ◽  
Bart N. Lambrecht ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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