The preischemic combination of the sodium–hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size

There is increasing evidence for interactions among adenosine receptor subtypes in the brain and heart. The purpose of this study was to determine whether the adenosine A2a receptor modulates the infarct size-reducing effect of preischemic administration of adenosine receptor agonists in intact rat myocardium. Adult male rats were submitted to in vivo regional myocardial ischemia (25 min) and 2 h reperfusion. Vehicle-treated rats were compared with rats pretreated with the A1 agonist 2-chloro- N6-cyclopentyladenosine (CCPA, 10 μg/kg), the nonselective agonist 5′- N-ethylcarboxamidoadenosine (NECA, 10 μg/kg), or the A2a agonist 2-[4-(2-carboxyethyl)phenethylamino]-5′- N-methylcarboxamidoadenosine (CGS-21680, 20 μg/kg). Additional CCPA- and NECA-treated rats were pretreated with the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg), the A2a/A2b antagonist 4-(-2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM-241385, 1.5 mg/kg) or the A3 antagonist 3-propyl-6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523, 2 mg/kg). CCPA and NECA reduced myocardial infarct size by 50% and 35%, respectively, versus vehicle, but CGS-21680 had no effect. DPCPX blunted the bradycardia associated with CCPA and NECA, whereas ZM-241385 attenuated their hypotensive effects. Both DPCPX and ZM-241385 blocked the protective effects of CCPA and NECA. The A3 antagonist did not alter the hemodynamic effects of CCPA or NECA, nor did it alter adenosine agonist cardioprotection. None of the antagonists alone altered myocardial infarct size. These findings suggest that although preischemic administration of an A2a receptor agonist does not induce cardioprotection, antagonism of the A2a and/or the A2b receptor blocks the cardioprotection associated with adenosine agonist pretreatment.

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563 Interleukin-6 and tumor necrosis factor alpha in relation to myocardial infarct size and collagen formation

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(03)90368-7 ◽

2003 ◽

Vol 2 (1) ◽

pp. 121

Author(s):

M PUHAKKA ◽

J MAGGA ◽

S HIETAKORPI ◽

I PENTTILA ◽

P UUSIMAA ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Infarct Size ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Myocardial Infarct ◽

Myocardial Infarct Size ◽

Necrosis Factor Alpha ◽

Collagen Formation ◽

Factor Alpha ◽

Necrosis Factor

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Faculty Opinions recommendation of Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1008695.372854 ◽

2006 ◽

Author(s):

Andreas Deussen

Keyword(s):

Infarct Size ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Phosphodiesterase Inhibitor ◽

Myocardial Infarct Size

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Faculty Opinions recommendation of Remote ischemic conditioning reduces myocardial infarct size in STEMI patients treated by thrombolysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725806212.793533019 ◽

2017 ◽

Author(s):

Zeljko Bosnjak

Keyword(s):

Infarct Size ◽

Myocardial Infarct ◽

Myocardial Infarct Size ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning

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

Cardiovascular Research ◽

10.1093/cvr/cvaa343 ◽

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.

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