scholarly journals Altered Susceptibility to Ischemia-Reperfusion Injury in Isolated-Perfused Hearts of Short-Term Diabetic Rats Associated With Changes in Non-enzymatic Antioxidants

2001 ◽  
Vol 85 (4) ◽  
pp. 435-442 ◽  
Author(s):  
Kam-Ming Ko ◽  
Duncan H.F. Mak ◽  
Michel K.T. Poon ◽  
Ho-Yan Yiu
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Enzymatic Antioxidants ◽  
Short Term ◽  
Perfused Hearts

scholarly journals The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats

2021 ◽  
Vol 22 (15) ◽  
pp. 7774
Author(s):  
Sevil Korkmaz-Icöz ◽  
Cenk Kocer ◽  
Alex A. Sayour ◽  
Patricia Kraft ◽  
Mona I. Benker ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Reperfusion Injury ◽  
Vascular Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Diabetic Rats ◽  
Organ Bath ◽  
Sodium Glucose Cotransporter

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.

The short term effects of resveratrol on ischemia–reperfusion injury in rat testis

2014 ◽  
Vol 49 (3) ◽  
pp. 484-489 ◽  
Author(s):  
Esin Yuluğ ◽  
Sibel Türedi ◽  
Ersagun Karagüzel ◽  
Ömer Kutlu ◽  
Ahmet Menteşe ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Short Term ◽  
Rat Testis ◽  
Short Term Effects

scholarly journals Inhibiting mTOR enhanced Cardiac STAT3 Phosphorylation at Site Ser 727 and Attenuated Myocardial Ischemia Reperfusion Injury in Diabetic Rats

2021 ◽  
Author(s):  
Xiang Xie ◽  
Zhongbao Zhao ◽  
Danyong Liu ◽  
Dengwen Zhang ◽  
Yi He ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mtor Inhibitor ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
H9c2 Cells ◽  
Sprague Dawley ◽  
Mtor Inhibition ◽  
Stat3 Phosphorylation

Abstract Background Reduced levels of myocardial STAT3 activity in diabetic hearts may contribute to the increased susceptibility to ischemia-reperfusion injury (I/RI). The protein mammalian target of rapamycin (mTOR) can regulate metabolism and cell processes and plays major roles in the dynamics of I/RI. However, the role of mTOR in regulation of myocardial STAT3 and thereby affect myocardial I/RI in diabetes at relatively late stages of the disease is unknown. Methods Diabetes was induced by Streptozotocin in Sprague-Dawley rats. Myocardial I/RI was achieved with coronary occlusion for 30 minutes and reperfusion for 2 hours in absence or presence of the mTOR inhibitor rapamycin. In vitro cardiomyocyte hypoxia/re-oxygenation (H/R) was established within H9C2 cells. Results In diabetic rats, the levels of troponin-I (Tn-I), lipid peroxidation products 15-F2t-Isoprostane (15-F2t-Iso) and MDA, and the expression of protein mTOR were all significantly increased,and SOD releasing, the expression of protein phosphorylation of STAT3(p-STAT3-Ser727) were both significantly decreased compared to non-diabetic rats. Myocardial I/RI significantly increased the infract size (IS) and further increased the mTOR activation and decreased p-STAT3-Ser727 compared to diabetic rats. The selective mTOR inhibitor rapamycin reversed these changes and conferred cardioprotective effect. In H9C2 cells, high glucose (HG) significantly increased lactic dehydrogenase (LDH) release, apoptosis cells, ROS release, activation of mTOR, and decreased p-STAT3-Ser727. H/R further increased cellular injury, mTOR knock-down significantly reduced H/R injury. Conclusion Myocardial mTOR was enhanced in diabetes and contributed to I/RI. mTOR inhibition attenuated myocardial I/RI through increasing p-STAT3-Ser727.

scholarly journals Adenosine A2Areceptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation

2008 ◽  
Vol 295 (5) ◽  
pp. H1825-H1833 ◽  
Author(s):  
Tyler H. Rork ◽  
Kori L. Wallace ◽  
Dylan P. Kennedy ◽  
Melissa A. Marshall ◽  
Amy R. Lankford ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mast Cell Degranulation ◽  
Chimeric Mice ◽  
Cgs 21680 ◽  
Perfused Hearts

Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A2Aadenosine receptors (A2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A2AAR+/+mice, A2AAR−/−mice, mast cell-deficient (KitW-sh/W-sh) mice, and chimeric mice prepared by transplanting bone marrow from A2AAR−/−or A2AAR+/+mice to radiation-ablated A2AAR+/+mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 ± 2% to 24 ± 2% and 22 ± 2% in ATL146e- and CGS-21680-treated hearts, respectively ( P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A2AAR−/−hearts and in hearts from chimeric mice with A2AAR−/−bone marrow. Vehicle-treated KitW-sh/W-shmice had lower IS (11 ± 3%) than WT mice, and ATL146e had no significant protective effect (16 ± 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation.

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