Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery

Váradi, Judit; Lekli, István; Juhász, Béla; Bácskay, Ildikó; Szabó, G.; Gesztelyi, Rudolf; Szendrei, Levente; Varga, Edit; Bak, István; Foresti, Roberta; Motterlini, Roberto; Tósaki, Árpád

doi:10.1016/j.lfs.2007.01.047

Cited by 52 publications

(45 citation statements)

References 58 publications

(55 reference statements)

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“…Several reports have corroborated the protective role that exogenously applied CO plays in many tissues including the cardiac and vascular compartments (Wu and Wang 2005;Kohmoto et al 2006;Musameh et al 2006;Ryter et al 2007;Chora et al 2007;Varadi et al 2007). As a consequence, several experimental systems have tested the possibility that this gaseous molecule, released in small amounts within biological fluids, might serve as a new therapeutic agent (Schober et al 2006;Bani-Hani et al 2006).…”

Section: Discussionmentioning

confidence: 89%

Acute myocardial infarction in streptozotocin-induced hyperglycaemic rats: protection by a carbon monoxide-releasing molecule (CORM-3)

Filippo

Perretti

Rossi

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Here, we have studied the effects of a carbon monoxide-releasing molecule (CORM-3, tricarbonylchloro(glycinato)ruthenium(II)) on acute myocardial ischemia/reperfusion (I/R) injury in hyperglycaemic streptozotocin-treated rats (STZ rats). Occlusion of the left descending coronary artery for 25 min followed by a 2-h reperfusion in STZ-induced hyperglycaemic rats was used as the model. CORM-3 and its inactive counterpart (iCORM-3) were administered 1 h prior to ischemia. The parameters measured included myocardial infarct size (IS) and a selection of inflammatory, oxidative markers and endothelial progenitor cells (CD34⁺ and CD117/c-kit⁺. In STZ-induced hyperglycaemic rats, occlusion of the left descending coronary artery caused injury of the myocardial tissue with an IS of ~70%, expressed as fraction of the area at risk. Given intraperitoneally 1 h prior to ischemia, CORM-3 (2-8 mg/kg) afforded significant dose-dependent cardio-protection. Specifically, pre-treatment with CORM-3 reduced infarct size by 14 ± 0.6%, 34 ± 1% and 53 ± 1.6% for doses of 2, 4 and 8 mg/kg, respectively. A negative control (iCORM-3) failed to prevent the cardiac damage induced by I/R. CORM-3 pre-treatment augmented cardiac heme oxygenase-1 (HO-1) protein levels and was associated with an increased number of CD34⁺- and CD117/c-kit⁺-positive immunostaining. Modulation of these markers was associated with augmented cardiac eNOS expression and levels of the cytokines TNF-α and IL-1 beta. CORM-3 afforded significant cardio-protection against acute myocardial infarction in STZ-induced hyperglycaemic rats through liberation of small amounts of CO. Of interest, CORM-3 promoted recruitment of the endogenous endothelial progenitor cells within the myocardium, possibly through modulation of cardiac HO-1 and eNOS expression and/or function.

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Section: Discussionmentioning

confidence: 89%

Acute myocardial infarction in streptozotocin-induced hyperglycaemic rats: protection by a carbon monoxide-releasing molecule (CORM-3)

Filippo

Perretti

Rossi

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The ex vivo and in vivo experiments conducted with models of cardiac ischemia highlighted the protective pharmacological properties of CO carriers. In a mouse model of myocardial infarction by coronary artery occlusion, intravenous infusion of CO-RM3 before reperfusion reduced infarct size, fibrillation and tachycardia [9,10,12]. These cardioprotective mechanisms mediated by CO-RMs probably involve a direct effect of CO, probably through its interactions with potassium channels [15].…”

Section: Discussionmentioning

confidence: 96%

“…It has recently been shown that CO-releasing molecules (CO-RMs) also deliver CO, and these compounds have since emerged as potential therapeutic agents for the treatment of various cardiovascular disorders [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Berne¹,

Lauzier²,

Rochette³

et al. 2012

Cell Physiol Biochem

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Carbon monoxide (CO) is believed to mediate many of the cytoprotective effects attributed to the activation of heme oxygenase (HO-1), the enzyme responsible for CO production. Recently, the study of CO-releasing molecules (CO-RMs) has provided a new approach for the delivery of CO. In the present study, we examined whether the cardioprotective properties of CO-RM2 in isolated rat hearts subjected to an ischemia-reperfusion (I/R) sequence were associated with the presence of CO. In addition, the antioxidant properties of CO-RM2 were evaluated. In hearts pretreated with CO-RM2, the improvement in contractile function at the end of the reperfusion period after 20 min of global total ischemia was significantly greater than in controls. These beneficial effects were accompanied by a reduction in 1) LDH activity release 2) infarct size 3) ventricular superoxide production. The improvement in myocardial function and the reduction in oxidative stress were not observed when hearts were pretreated with inactivated CO-RM2 (iCO-RM2). Additionally, CO-RM2, but not iCO-RM2, was found to exert antioxidant properties. These results suggest that the production of CO is a necessary factor in the cardioprotective and antioxidant actions of CO-releasing compound. These results may open up new ground for a novel class of cardioprotective compounds.

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“…Regarding the cardiovascular system, it has been notably reported that endogenous production as well as acute breathing of CO could be protective during myocardial ischemia-reperfusion [3][4][5][6][7][8][9][10]. However, CO is also a ubiquitous environmental pollutant present in automobile emissions, industrial gases as well as cigarette smoke [11].…”

Section: Introductionmentioning

confidence: 99%

Carbon Monoxide Pollution Impairs Myocardial Perfusion Reserve: Implication of Coronary Endothelial Dysfunction

Meyer

Boissière²,

Tanguy³

et al. 2011

Cardiovasc Toxicol

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Chronic exposure to simulated urban CO pollution is reported to be associated with cardiac dysfunction. Despite the potential implication of myocardial perfusion alteration in the pathophysiology of CO pollution, the underlying mechanisms remain today still unknown. Therefore, the aim of this work was to evaluate the effects of prolonged exposure to simulated urban CO pollution on the regulation of myocardial perfusion. Cardiac hemodynamics and myocardial perfusion were assessed under basal conditions and during the infusion of a β-Adrenergic agonist. The effects of CO exposure on capillary density, coronary endothelium-dependent vasodilatation, eNOS expression and eNOS uncoupling were also evaluated. Our main results were that prolonged CO exposure was associated with a blunted myocardial perfusion response to a physiological stress responsible for an altered contractile reserve. The impairment of myocardial perfusion reserve was not accounted for a reduced capillary density but rather by an alteration in coronary endothelium-dependent vasorelaxation (-45% of maximal relaxation to ACh). In addition, though chronic CO exposure did not change eNOS expression, it significantly increased eNOS uncoupling. Therefore, the present work underlines the fact that chronic CO exposure, at levels found in urban air pollution, is associated with reduced myocardial perfusion reserve. This phenomenon is explained at the coronary-vessel level by deleterious effects of CO exposure on the endothelium NO-dependent vasorelaxation via eNOS uncoupling.

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Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery

Cited by 52 publications

References 58 publications

Acute myocardial infarction in streptozotocin-induced hyperglycaemic rats: protection by a carbon monoxide-releasing molecule (CORM-3)

Acute myocardial infarction in streptozotocin-induced hyperglycaemic rats: protection by a carbon monoxide-releasing molecule (CORM-3)

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Carbon Monoxide Pollution Impairs Myocardial Perfusion Reserve: Implication of Coronary Endothelial Dysfunction

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