scholarly journals Neonatal Rat Hearts Cannot Be Protected by Ischemic Postconditioning

2015 ◽  
pp. 789-794 ◽  
Author(s):  
J. DOUL ◽  
Z. CHARVÁTOVÁ ◽  
I. OŠŤÁDALOVÁ ◽  
M. KOHUTIAR ◽  
H. MAXOVÁ ◽  
...  
Keyword(s):  
Isometric Force ◽  
Ischemia Reperfusion ◽  
Force Transducer ◽  
Global Ischemia ◽  
Ischemic Postconditioning ◽  
Neonatal Rat ◽  
Postnatal Life ◽  
Protective Effects ◽  
Rat Hearts ◽  
Ldh Release

Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, rat hearts isolated on days 1, 4, 7 and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol was then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life.

Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning

2008 ◽  
Vol 295 (3) ◽  
pp. H1330-H1340 ◽  
Author(s):  
Qian Chen Yong ◽  
Shiau Wei Lee ◽  
Chun Shin Foo ◽  
Kay Li Neo ◽  
Xin Chen ◽  
...  
Keyword(s):  
Hydrogen Sulphide ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Early Period ◽  
Ischemic Postconditioning ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Rat Hearts ◽  
Underlying Mechanisms

The present study aimed to investigate the role of hydrogen sulphide (H2S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous H2S production with d-l-propargylglycine. Moreover, IPostC significantly stimulated H2S synthesis enzyme activity during the early period of reperfusion. However, d-l-propargylglycine only attenuated the IPostC-induced activation of PKC-α and PKC-ε but not that of PKC-δ, Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous H2S contributes partially to the cardioprotection of IPostC via stimulating PKC-α and PKC-ε. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous NaHS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 μM) or PKC with chelerythrine (10 μM) abolished the cardioprotection induced by H2S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous H2S contributes to IPostC-induced cardioprotection. H2S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways.

scholarly journals Protective Effects of Topiroxostat on an Ischemia-Reperfusion Model of Rat Hearts

2018 ◽  
Vol 82 (4) ◽  
pp. 1101-1111 ◽  
Author(s):  
Shogo Tanno ◽  
Kenshiro Yamamoto ◽  
Yasutaka Kurata ◽  
Maya Adachi ◽  
Yumiko Inoue ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Rat Hearts

scholarly journals Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3β/Nrf2 Pathway in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Rong Chen ◽  
Yun-yan Zhang ◽  
Jia-nan Lan ◽  
Hui-min Liu ◽  
Wei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intestinal Ischemia ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Nrf2 Pathway ◽  
Intestinal Ischemia Reperfusion

Aims. Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. Methods. C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu’s score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3β/Nrf2 pathway. Results. IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3β, induced Nrf2 nuclear translocation, and upregulated HO-1 and NQO1 expression, thus providing protective effects against IIR injury by suppressing oxidative stress. Consistently, the beneficial effects of IPO were abolished by pretreatment with 3-methyladenine, SC66, and brusatol, potent inhibitors of autophagy, Akt, and Nrf2, respectively. Conclusion. Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3β, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.

scholarly journals Ischemic Postconditioning as a Novel Avenue to Protect against Brain Injury after Stroke

2009 ◽  
Vol 29 (5) ◽  
pp. 873-885 ◽  
Author(s):  
Heng Zhao
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Mitogen Activated Protein ◽  
Cerebral Ischemic

Ischemic postconditioning initially referred to a stuttering reperfusion performed immediately after reperfusion, for preventing ischemia/reperfusion injury in both myocardial and cerebral infarction. It has evolved into a concept that can be induced by a broad range of stimuli or triggers, and may even be performed as late as 6 h after focal ischemia and 2 days after transient global ischemia. The concept is thought to be derived from ischemic preconditioning or partial/gradual reperfusion, but in fact the first experiment for postconditioning was carried out much earlier than that of preconditioning or partial/gradual reperfusion, in the research on myocardial ischemia. This review first examines the protective effects and parameters of postconditioning in various cerebral ischemic models. Thereafter, it provides insights into the protective mechanisms of postconditioning associated with reperfusion injury and the Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive K+ (KATP) channel cell signaling pathways. Finally, some open issues and future challenges regarding clinical translation of postconditioning are discussed.

scholarly journals SDF-1/CXCR4 mediates acute protection of cardiac function through myocardial STAT3 signaling following global ischemia/reperfusion injury

2011 ◽  
Vol 301 (4) ◽  
pp. H1496-H1505 ◽  
Author(s):  
Chunyan Huang ◽  
Hongmei Gu ◽  
Wenjun Zhang ◽  
Mariuxi C. Manukyan ◽  
Weinian Shou ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Global Ischemia ◽  
Dependent Manner ◽  
Protective Effects ◽  
Stat3 Signaling ◽  
Stromal Cell Derived Factor ◽  
Myocardial Ischemia Reperfusion ◽  
Dose Dependent ◽  
Cxcr4 Axis

Stromal cell-derived factor-1α (SDF-1) has been reported to mediate cardioprotection through the mobilization of stem cells into injured tissue and an increase in local angiogenesis after myocardial infarction. However, little is known regarding whether SDF-1 induces acute protection following global myocardial ischemia/reperfusion (I/R) injury and if so, by what molecular mechanism. SDF-1 binding to its cognate receptor CXCR4 has been shown to activate STAT3 in a variety of cells. STAT3 is a cardioprotective factor and may mediate SDF-1/CXCR4-induced acute protection. We hypothesized that SDF-1 would improve myocardial function through CXCR4-increased STAT3 activation following acute I/R. Isolated mouse hearts were subjected to 25-min global ischemia/40-min reperfusion and divided into groups of 1) vehicle; 2) SDF-1; 3) AMD3100, a CXCR4 inhibitor; 4) SDF-1 + AMD3100; 5) Stattic, a STAT3 inhibitor; 6) SDF-1 + Stattic; 7) cardiomyocyte-restricted ablation of STAT3 (STAT3KO); 8) STAT3KO + SDF-1; 9) Ly294002, an inhibitor of the Akt pathway; and 10) SDF-1 + Ly294002. Reagents were infused into hearts within 5 min before ischemia. SDF-1 administration significantly improved postischemic myocardial functional recovery in a dose-dependent manner. Additionally, pretreatment with SDF-1 reduced cardiac apoptotic signaling and increased myocardial STAT3 activation following acute I/R. Inhibition of the SDF-1 receptor CXCR4 neutralized these protective effects by SDF-1 in hearts subjected to I/R. Notably, inhibition of the STAT3 pathway or use of STAT3KO hearts abolished SDF-1-induced acute protection following myocardial I/R. Our results represent the first evidence that the SDF-1/CXCR4 axis upregualtes myocardial STAT3 activation and, thereby, mediates acute cardioprotection in response to global I/R.

PAR-2 activation at the time of reperfusion salvages myocardium via an ERK1/2 pathway in in vivo rat hearts

2007 ◽  
Vol 293 (5) ◽  
pp. H2845-H2852 ◽  
Author(s):  
Rong Jiang ◽  
Amanda Zatta ◽  
Hajime Kin ◽  
Ningping Wang ◽  
James G. Reeves ◽  
...  
Keyword(s):  
Infarct Size ◽  
Kinase Inhibitor ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Rat Hearts ◽  
Sparing Effect ◽  
Myocardial Ischemia Reperfusion

Protease-activated receptor-2 (PAR-2) may have proinflammatory effects in some tissues and protective effects in other tissues. The role of PAR-2 in in vivo myocardial ischemia-reperfusion has not yet been determined. This study tested the hypothesis that PAR-2 activation with the PAR-2 agonist peptide SLIGRL (PAR-2 AP) reduces myocardial infarct size when given at reperfusion in vivo, and this cardioprotection involves the ERK1/2 pathway. Anesthetized rats were randomly assigned to the following groups with 30 min of regional ischemia and 3 h reperfusion: 1) control with saline; 2) vehicle (DMSO); 3) PAR-2 AP, 1 mg/kg given intravenously 5 min before reperfusion; 4) scrambled peptide (SP), 1 mg/kg; 5) the ERK1/2 inhibitor PD-98059 (PD), 0.3 mg/kg given 10 min before reperfusion; 6) the phosphatidylinositol 3-kinase inhibitor LY-294002 (LY), 0.3 mg/kg given 10 min before reperfusion; 7) PD + PAR-2 AP, 0.3 mg/kg PD given 5 min before PAR-2 AP; 8) LY + PAR-2 AP, 0.3 mg/kg LY given 5 min before PAR-2 AP; 9) chelerythrine (Chel) alone, 5 mg/kg given 10 min before reperfusion; and 10) Chel + PAR-2 AP, Chel was given 5 min before PAR-2 AP (10 min before reperfusion). Activation of ERK1/2, ERK5, Akt, and the downstream targets of ERK1/2 [P90 RSK and bcl-xl/bcl-2-associated death promoter (BAD)] was determined by Western blot analysis in separate experiments. PAR-2 AP significantly reduced infarct size compared with control (36 ± 2% vs. 53 ± 1%, P < 0.05), and SP had no effect on infarct size (53 ± 3%). PAR-2 AP significantly increased phosphorylation of ERK1/2, p90RSK, and BAD but not Akt or ERK5. Accordingly, the infarct-size sparing effect of PAR-2 AP was abolished by PD (PAR-2 AP, 36 ± 2% vs. PD + PAR-2 AP, 50 ± 1%; P < 0.05) and by Chel (Chel + PAR-2 AP, 58 ± 2%) but not by LY (PAR-2 AP, 36 ± 2% vs. LY + PAR-2 AP, 38 ± 3%; P > 0.05). Therefore, PAR-2 activation is cardioprotective in the in vivo rat heart ischemia-reperfusion model, and this protection involves the ERK1/2 pathway and PKC.

scholarly journals Testosterone enhances estradiol's cardioprotection in ovariectomized rats

2011 ◽  
Vol 212 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Aiying Liu ◽  
Liping Gao ◽  
Shoulei Kang ◽  
Ying Liu ◽  
Chuanying Xu ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Testosterone Replacement ◽  
Ovariectomized Rats ◽  
Sham Operation ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Ovx Rats ◽  
Ldh Release

After menopause, the development of cardiovascular disease (CVD) is due not only to estrogen decline but also to androgen decline. This study examined the effects of either estradiol (E2) or testosterone replacement alone or E2–testosterone combination on isolated myocytes in ovariectomized (Ovx) rats subjected to ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are associated with β2-adrenoceptor (β2-AR). Five groups of adult female Sprague–Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats, Ovx rats with E2 40 μg/kg per day (Ovx+E), Ovx rats with testosterone 150 μg/kg per day (Ovx+T), and Ovx rats with E2 40 μg/kg per day+testosterone 150 μg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release, percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of all groups subjected to I/R. Then, we determined the above indices and contractile function with or without a selective β2-AR antagonist ICI 118 551. We also determined the expression of β2-AR. Our data show that either E2 or testosterone replacement alone or E2 and testosterone in combination decreased the LDH release, increased the percentage of rod-shaped cells, reduced apoptotic cells (%), and combination treatment appeared to be more effective than either E2 or testosterone replacement alone. ICI 118 551 abolished the effects of the three. Combination supplementation also enhanced the expression of β2-AR. We concluded that in Ovx rats, testosterone enhances E2's cardioprotection, while E2 and testosterone in combination was more effective and the protective effects may be associated with β2-AR. The study highlights the potential therapeutic application for CVD in postmenopausal women.

Hyperthermia-Induced Cardioprotection Is Potentiated by Ischemic Postconditioning in Rats

2009 ◽  
Vol 234 (5) ◽  
pp. 573-581 ◽  
Author(s):  
Yukichi Murozono ◽  
Naohiko Takahashi ◽  
Tetsuji Shinohara ◽  
Tatsuhiko Ooie ◽  
Yasushi Teshima ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Ischemic Postconditioning ◽  
Initial Moment ◽  
Protective Effects ◽  
Perfused Heart ◽  
Ventricular Performance ◽  
Akt Phosphorylation

We tested the hypothesis that the protective effects of hyperthermia (HT) could be augmented by ischemic postconditioning (PostC) via enhancement of reperfusion-induced Akt phosphorylation. The role of the mitoKATP channel as an effecter to protect hearts against ischemia/reperfusion injury was also investigated. In isolated perfused heart experiments using a Langendorff apparatus, 30 min of no-flow global ischemia was followed by 120 min of reperfusion. Ischemic PostC, 5 cycles of 10-sec reperfusion/10-sec ischemia, was achieved at the initial moment of reperfusion. Hyperthermia (HT, 43°C for 20 min) was applied 24 hr before ischemia onset. Ischemic PostC alone did not show significant protection, but HT did. The HT-induced protection in terms of infarct size, recovery of left ventricular performance, amount of released creatine kinase and apoptosis were enhanced by ischemic PostC. These protective effects were consistent with the levels of Akt phosphorylation 7 min after reperfusion and were completely blocked by the pretreatment with the phosphatidylinositol 3-kinase inhibitor wortmannin. HT-induced protection was also completely abolished by concomitant perfusion with 5-hydroxydecanoate (5HD, 100 μM), an inhibitor of the mitochondrial ATP-sensitive potassium (mitoKATP) channel. However, the potentiated protection by ischemic PostC remained, even in the presence of 5HD. In conclusion, ischemic PostC could potentiate the protective effects of HT possibly via enhancement of reperfusion-induced Akt phosphorylation. Although the opening of the mitoKATP channel is predominantly involved as an effecter in HT-induced protection, potentiated protection by ischemic PostC may involve mechanisms other than the mitoKATP channel.

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