Reduction of myocardial leukocyte accumulation and myocardial infarct size following administration of BAY u3405, a thromboxane A2 receptor antagonist, in myocardial ischaemia-reperfusion injury

1993 ◽  
Vol 39 (3-4) ◽  
pp. 143-149 ◽  
Author(s):  
F. Squadrito ◽  
M. Ioculano ◽  
D. Altavilla ◽  
B. Zingarelli ◽  
P. Canale ◽  
...  
Keyword(s):  
Infarct Size ◽  
Receptor Antagonist ◽  
Myocardial Ischaemia ◽  
Myocardial Infarct ◽  
Thromboxane A2 ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Thromboxane A2 Receptor ◽  
Leukocyte Accumulation ◽  
Ischaemia Reperfusion

scholarly journals Hydralazine protects the heart against acute ischaemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission

2021 ◽  
Author(s):  
Siavash Beikoghli Kalkhoran ◽  
Janos Kriston-Vizi ◽  
Sauri Hernandez-Resendiz ◽  
Gustavo E Crespo-Avilan ◽  
Ayeshah A Rosdah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Mitochondrial Fission ◽  
Vehicle Control ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Pre Treatment ◽  
Apoptotic Effects

Abstract Aims Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission. Methods and results Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine attenuated mitochondrial fission and cell death induced by oxidative stress, but this effect was absent in MEFs deficient in the mitochondrial fission protein, Drp1. Molecular docking and surface plasmon resonance studies demonstrated binding of hydralazine to the GTPase domain of the mitochondrial fission protein, Drp1 (KD 8.6±1.0 µM), and inhibition of Drp1 GTPase activity in a dose-dependent manner. In isolated adult murine cardiomyocytes subjected to simulated IRI, hydralazine inhibited mitochondrial fission, preserved mitochondrial fusion events, and reduced cardiomyocyte death (hydralazine 24.7±2.5% vs. control 34.1±1.5%, P=0.0012). In ex vivo perfused murine hearts subjected to acute IRI, pre-treatment with hydralazine reduced myocardial infarct size (as % left ventricle: hydralazine 29.6±6.5% vs. vehicle control 54.1±4.9%, P=0.0083), and in the murine heart subjected to in vivo IRI, the administration of hydralazine at reperfusion, decreased myocardial infarct size (as % area-at-risk: hydralazine 28.9±3.0% vs. vehicle control 58.2±3.8%, P<0.001). Conclusion We show that, in addition to its antioxidant and anti-apoptotic effects, hydralazine, confers acute cardioprotection by inhibiting IRI-induced mitochondrial fission, raising the possibility of repurposing hydralazine as a novel cardioprotective therapy for improving post-infarction outcomes.

scholarly journals Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling

2017 ◽  
Vol 43 (3) ◽  
pp. 1140-1151 ◽  
Author(s):  
Sumin Gao ◽  
Leyun Zhan ◽  
Zhengchao Yang ◽  
Ruili Shi ◽  
Haobo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Ischaemia ◽  
Nuclear Translocation ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Enzyme Release ◽  
Ischaemia Reperfusion ◽  
Myocardial Oxidative Stress ◽  
Creatine Kinase Mb

Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. Results: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). Conclusion: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.

scholarly journals Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia/reperfusion in rats

2007 ◽  
Vol 77 (1) ◽  
pp. 44-53 ◽  
Author(s):  
J. E. Baker ◽  
J. Su ◽  
A. Hsu ◽  
Y. Shi ◽  
M. Zhao ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion

Follistatin, An Activin A Binding Protein, Reduces Infarct Size in Myocardial Ischaemia Reperfusion Injury

2011 ◽  
Vol 20 (1) ◽  
pp. 36
Author(s):  
Yi Chen ◽  
Christine Rothnie ◽  
Denise Spring ◽  
Edward Verrier ◽  
Kylie Vernados ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Binding Protein ◽  
Activin A ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion
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