scholarly journals The protective effects of phosphodiesterase-5 inhibitor, sildenafil on post-resuscitation cardiac dysfunction of cardiac arrest: by regulating the miR-155-5p and miR-145-5p

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Yong He ◽  
Guoxing Wang ◽  
Chuang Li ◽  
Yuxing Wang ◽  
Qian Zhang
Keyword(s):  
Survival Rate ◽  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Oxygen Metabolism ◽  
Spontaneous Circulation ◽  
Sham Operation ◽  
Protective Effects ◽  
Sham Operation Group

Abstract Background MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions. Methods Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury. Results Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions. Conclusions Sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.

scholarly journals The Protective Effects of Phosphodiesterase-5 Inhibitor, Sildenafil on Post-resuscitation Cardiac Dysfunction of Cardiac Arrest: By Regulating the MiR-155-5p and MiR-145-5p

2020 ◽  
Author(s):  
Yong He ◽  
Guoxing Wang ◽  
Chuang Li ◽  
YUXING WANG ◽  
QIAN ZHANG
Keyword(s):  
Survival Rate ◽  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Oxygen Metabolism ◽  
Spontaneous Circulation ◽  
Sham Operation ◽  
Protective Effects ◽  
Sham Operation Group

Abstract Background: MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.Methods: Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n= 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20mg/kg L) group (n=8), saline (SA group, n=8); and sham operation group (sham group, n=8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury.Results: Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-hour survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.Conclusions: sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-hour survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.

scholarly journals Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1-Mediated Mitochondrial Fission after Cardiac Arrest-Induced Myocardial Damage

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wu ◽  
Hui Chen ◽  
Jiahong Qin ◽  
Nan Chen ◽  
Shiqi Lu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Mitochondrial Dysfunction ◽  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Specific Inhibitor ◽  
Myocardial Damage ◽  
Spontaneous Circulation ◽  
Flavonoid Compound

Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA-induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi-1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin-afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1-mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post-CA myocardial injury.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

Zingerone Alleviates Myocardial Ischemia/Reperfusion Injury

2021 ◽  
Vol 19 (4) ◽  
pp. 543-549
Author(s):  
Fanglin Luo ◽  
Shunxiang Luo ◽  
Yanqing Wu
Keyword(s):  
Myocardial Infarction ◽  
Proinflammatory Cytokine ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Cytokine Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Using a rat model, we have explored the underlying mechanism of ischemia/reperfusion (I/R)-mediated myocardial infarction and assessed the protective potential of zingerone. The results show that zingerone exhibits not only the myocardial protective effect, but also antioxidative and anti-inflammatory effects by suppression of markers of oxidation and proinflammatory cytokine release. Zingerone promotes protective effects against I/R-induced myocardial infarction by regulating Nrf2/HO-1 and NF-κB signaling pathways. These findings provide novel insights into the effects of zingerone on the cardioprotective mechanism of myocardial injury after I/R and may open new avenues for myocardial infarction treatment.

Protective effects of 5-(N,N-dimethyl)amiloride on ischemia-reperfusion injury in hearts

1990 ◽  
Vol 258 (5) ◽  
pp. H1615-H1619 ◽  
Author(s):  
H. P. Meng ◽  
G. N. Pierce
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Significant Rise ◽  
Similar Degree ◽  
Protective Effects ◽  
Tension Development ◽  
Right Ventricular Wall ◽  
Dimethyl Amiloride

An Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)amiloride (DMA), was used to probe the possible role of Na(+)-H+ exchange in ischemia-reperfusion injury in coronary perfused isolated rat right ventricular wall. In DMA-untreated hearts, 60 min of ischemia resulted in a significant rise in testing tension (RT: 174 +/- 8% of preischemic level). Thirty minutes of reperfusion further increased RT (273 +/- 12%) and induced a poor recovery in developed tension (DT: 28 +/- 4%). Both the rate of tension development and relaxation (+dT/dt and -dT/dt) recovered to a similar degree. When 1, 5, or 20 microM DMA was included in the perfusate (3 min before ischemia and in the first 3 min of reperfusion), the maximal postischemic RT of the heart was reduced to 204 +/- 21, 166 +/- 15, and 139 +/- 45% of the preischemic levels (P less than 0.05), respectively, and DT was 39 +/- 3, 63 +/- 10, and 79 +/- 8% of the preischemic levels (P less than 0.05), respectively. Similar qualitative recovery of +/- dT/dt was observed. Recovery was similar if DMA was present only during reperfusion. DMA treatment also significantly protected against creatine phosphokinase release during reperfusion. The results demonstrate that DMA can significantly protect the heart during the initial stages of reperfusion. The data suggest that Na(+)-H+ exchange may play an important role in the development of cardiac dysfunction and damage during the first minutes of reperfusion.

scholarly journals The role of PI3K-mediated AMPA receptor changes in post-conditioning of propofol in brain protection

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chenxu Wang ◽  
Ying Wei ◽  
Yuan Yuan ◽  
Yonghao Yu ◽  
Keliang Xie ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Sham Operation ◽  
Short Term ◽  
Selective Antagonist ◽  
Cerebral Artery Occlusion

Abstract Background We aimed to study the role of amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) glutamate receptor 2 (GluR2) subunit trafficking, and activity changes in short-term neuroprotection provided by propofol post-conditioning. We also aimed to determine the role of phosphoinositide-3-kinase (PI3K) in the regulation of these processes. Methods Rats underwent 1 h of focal cerebral ischemia followed by 23 h of reperfusion were randomly divided into 6 groups (n = 36 per group): sham- operation (S), ischemia–reperfusion (IR), propofol (P group, propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion), and LY294002 (PI3K non-selective antagonist) + sham (L + S, LY294002 of 1.5 mg/kg was infused 30 min before sham operation), LY294002+ ischemia–reperfusion (L + IR, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion), LY294002 + IR + propofol (L + P, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion and propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion). Results Compared with group IR, rats in group P had significant lower neurologic defect scores and infarct volume. Additionally, consistent with enhanced expression of PI3K-AMPAR GluR2 subunit complex substances in ipsilateral hippocampus, GluR2 subunits showed increased levels in both the plasma and postsynaptic membranes of neurons, while pGluR2 expression was reduced in group P. Furthermore, LY294002, the PI3K non-selective antagonist, blocked those effects. Conclusion These observations demonstrated that propofol post-conditioning revealed acute neuroprotective role against transient MCAO in rats. The short-term neuroprotective effect was contributed by enhanced GluR2 subunits trafficking to membrane and postsynaptic membranes of neurons, as well as down-regulated the expression of pGluR2 in damaged hippocampus. Finally, the above-mentioned protective mechanism might be contributed by increased combination of PI3K to AMPAR GluR2 subunit, thus maintained the expression and activation of AMPAR GluR2 in the ipsilateral hippocampus.

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