Measurement of Radical-Scavenging Ability in Small Bowel Ischemia/Reperfusion Injury in Rats Using an In Vivo and Ex Vivo Electron Paramagnetic Resonance Technique

Background: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the build-up of acidic metabolites results in decreased intracellular and extracellular pH that can reach as low as 6.0-6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly impacts cardiac function. Methods: We used genetic and pharmacological methods to investigate the role of acid sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole organ level. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and post-conditioning therapeutic agents. Results: Analysis of human complex trait genetics indicate that variants in the ASIC1 genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using hiPSC-CMs in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacological inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction (MI) and two models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as pre- or post-conditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no impact on cardiac ion channels regulating baseline electromechanical coupling and physiological performance. Conclusions: Collectively, our data provide compelling evidence for a novel pharmacological strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

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A continuous in vivo model of ischemia/reperfusion induced free radical formation in the cerebral spinal fluid (CSF) of pigs using spin-trapping agents and electron paramagnetic resonance (EPR) techniques

Free Radical Biology and Medicine ◽

10.1016/0891-5849(90)90516-l ◽

1990 ◽

Vol 9 ◽

pp. 97 ◽

Cited By ~ 11

Author(s):

D.G. Lange ◽

J.R. Kirsch ◽

M.A. Helfaer ◽

R.J. Traystman

Keyword(s):

Electron Paramagnetic Resonance ◽

Free Radical ◽

Cerebral Spinal Fluid ◽

Ischemia Reperfusion ◽

Spin Trapping ◽

In Vivo Model ◽

Paramagnetic Resonance ◽

Free Radical Formation ◽

Electron Paramagnetic

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P1742Experimental ischemic stroke in rats induce myocardial contractile dysfunction in vivo and ex vivo and increase cardiac vulnerability to ischemia-reperfusion injury ex vivo

European Heart Journal ◽

10.1093/eurheartj/ehx502.p1742 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

A. Meloux ◽

E. Rigal ◽

L. Rochette ◽

Y. Cottin ◽

Y. Bejot ◽

...

Keyword(s):

Ischemic Stroke ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ex Vivo ◽

Ischemia Reperfusion ◽

Contractile Dysfunction ◽

Myocardial Contractile

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Anastatin Derivatives Alleviate Myocardial Ischemia-Reperfusion Injury via Antioxidative Properties

Molecules ◽

10.3390/molecules26164779 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4779

Author(s):

Ying Fu ◽

Cai Zhao ◽

Rengui Saxu ◽

Chaoran Yao ◽

Lianbo Zhao ◽

...

Keyword(s):

Myocardial Ischemia ◽

Ischemia Reperfusion Injury ◽

Antioxidant Activities ◽

Ischemia Reperfusion ◽

Radical Scavenging ◽

Serum Lactate Dehydrogenase ◽

Antioxidant Power ◽

Myocardial Ischemia Reperfusion

(±)-Anastatins A and B are flavonoids isolated from Anastatica hierochuntica. In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their preliminary antioxidant activities were evaluated. In the present study, the protective effect of myocardial ischemia-reperfusion (I/R) and the systematic antioxidant capacity of 24 derivatives were further studied. Compound 13 was the most potent among all the compounds studied, which increased the survival of H9c2 cells to 80.82%. The antioxidant capability of compound 13 was evaluated in ferric reducing antioxidant power, 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-picrylhydrazyl assays. It was observed that compound 13 significantly reduced infarcted areas and improved histopathological and electrocardiogram changes in rats with myocardial I/R injury. Moreover, compound 13 decreased the leakage rates of serum lactate dehydrogenase, creatine kinase, and malonyldialdehyde from rat myocardial tissues and increased the level of glutathione and superoxide dismutase activities following myocardial I/R injury in rats. Taken together, we concluded that compound 13 had potent cardioprotective effects against myocardial I/R injury both in vitro and in vivo owing to its extensive antioxidant activities.

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The Contribution of Electron Paramagnetic Resonance to Melanoma Research

Journal of Skin Cancer ◽

10.1155/2011/273280 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Quentin Godechal ◽

Bernard Gallez

Keyword(s):

Electron Paramagnetic Resonance ◽

Skin Cancer ◽

Ex Vivo ◽

Current Method ◽

Basic Knowledge ◽

Ultraviolet Rays ◽

Paramagnetic Resonance ◽

Endogenous Substrate ◽

Electron Paramagnetic

The incidence of malignant melanoma, the most dangerous form of skin cancer, is rising each year. However, some aspects of the tumor initiation and development are still unclear, and the current method of diagnosis, based on the visual aspect of the tumor, shows limitations. For these reasons, developments of new techniques are ongoing to improve basic knowledge on the disease and diagnosis of tumors in individual patients. This paper shows how electron paramagnetic resonance (EPR), a method able to detect free radicals trapped in melanin pigments, has recently brought its unique value to this specific field. The general principles of the method and the convenience of melanin as an endogenous substrate for EPR measurements are explained. Then, the way by which EPR has recently helped to assess the contribution of ultraviolet rays (UVA and UVB) to the initiation of melanoma is described. Finally, we describe the improvements of EPR spectrometry and imaging in the detection and mapping of melanin pigments insideex vivoandin vivomelanomas. We discuss how these advances might improve the diagnosis of this skin cancer and point out the present capabilities and limitations of the method.

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