Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries.

Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms by which KYNA may be protective are still unclear.

Combined Metabolipidomic and Machine Learning Approach in a Rat Model of Stroke Reveals a Deleterious Impact of Brain Injury on Heart Metabolism.

Cardiac complications are frequently found following a stroke in humans whose pathophysiological mechanism remains poorly understood. We used machine learning to analyse a large set of data from a metabolipidomic study assaying 630 metabolites in a rat stroke model to investigate metabolic changes affecting the heart within 72 h after a stroke. Twelve rats undergoing a stroke and 28 rats undergoing the sham procedure were investigated.

DRP1 haploinsufficiency attenuates cardiac ischemia/reperfusion injuries.

Mitochondrial dynamics is a possible modulator of myocardial ischemia/reperfusion injuries (IRI). We previously reported that mice partially deficient in the fusion protein OPA1 exhibited higher IRI. Therefore, we investigated whether deficiency in the fission protein DRP1 encoded by Dnm1l gene would affect IRI in Dnm1l+/- mouse.

Tryptophane-kynurenine pathway in the remote ischemic conditioning mechanism.

The actual protective mechanisms underlying cardioprotection with remote ischemic conditioning (RIC) remain unclear. Recent data suggest that RIC induces kynurenine (KYN) and kynurenic acid synthesis, two metabolites derived from tryptophan (TRP), yet a causal relation between TRP pathway and RIC remains to be established. We sought to study the impact of RIC on the levels of TRP and its main metabolites within tissues, and to assess whether blocking kynurenine (KYN) synthesis from TRP would inhibit RIC-induced cardioprotection.

Direct Rivaroxaban-Induced Factor XA Inhibition Proves to be Cardioprotective in Rats.

Background: Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear.

Remote Ischemic Conditioning in a Model of Severe Renal Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury is a leading cause of acute renal dysfunction. Remote ischemic conditioning (rIC) is known to protect organs exposed to I/R. We sought to investigate whether rIC would influence renal function recovery in a severe renal I/R injury rat model.

Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of Acute Myocardial Infarction.

Background: Inflammation plays a crucial role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. A clinical trial has recently reported a smaller infarct size in a cohort of patients with ST-segment elevation myocardial infarction (MI) treated with a short colchicine course. The mechanism underlying colchicine-induced cardioprotection in the early MI phase remains unclear.

Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model.

Background: Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain.

Objectives: To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries.

Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines.

Background: Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role.

Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone.

Objective: Myogenic tone (MT) of resistance arteries ensures autoregulation of blood flow in organs and relies on the intrinsic property of smooth muscle to contract in response to stretch. Nucleotides released by mechanical strain on cells are responsible for pleiotropic vascular effects, including vasoconstriction. Here, we evaluated the contribution of extracellular nucleotides to MT.

Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.

Introduction: Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels.

REMOTE ISCHEMIC CONDITIONING INFLUENCES MITOCHONDRIAL DYNAMICS.

Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission.

RISK and SAFE signaling pathway involvement in apolipoprotein A-I-induced cardioprotection.

Unlabelled: Recent findings indicate that apolipoprotein A-I (ApoA-I) may be a protective humoral mediator involved in remote ischemic preconditioning (RIPC). This study sought to determine if ApoA-I mediates its protective effects via the RISK and SAFE signaling pathways implicated in RIPC. Wistar rats were allocated to one of the following groups.

Modifications in rat plasma proteome after remote ischemic preconditioning (RIPC) stimulus: identification by a SELDI-TOF-MS approach.

Remote ischemic preconditioning's (RIPC) ability to render the myocardium resistant to subsequent prolonged ischemia is now clearly established in different species, including humans. Strong evidence suggests that circulating humoral mediators play a key role in signal transduction, but their identities still need to be established. Our study sought to identify potential circulating RIPC mediators using a proteomic approach.

Apolipoprotein a-I is a potential mediator of remote ischemic preconditioning.

Background: Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy in clinical settings. Despite convincing evidence of the critical role played by circulating humoral mediators, their actual identities remain unknown. In this study, we aimed to identify RIPC-induced humoral mediators using a proteomic approach.

Role of hypoxia inducible factor-1α in remote limb ischemic preconditioning.

Remote ischemic preconditioning (RIPC) has emerged as a feasible and attractive therapeutic procedure for heart protection against ischemia/reperfusion (I/R) injury. However, its molecular mechanisms remain poorly understood. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that plays a key role in the cellular adaptation to hypoxia and ischemia.

Endothelin-1 release during the early phase of reperfusion is a mediator of myocardial reperfusion injury.

Purpose: In acute myocardial infarction, left ventricular (LV) unloading reduces endothelin-1 (ET-1) release. We tested that endogenous ET-1 released during acute myocardial infarction might mediate ischemia/reperfusion (I/R) injury by stimulating increased intracellular calcium concentration, [Ca(2+)]i, and apoptosis.

Methods: Rabbits were subjected to 1 h of coronary artery occlusion followed by 3 h of reperfusion.

Endoplasmic reticulum stress pathway involvement in local and remote myocardial ischemic conditioning.

Remote ischemic perconditioning (RIPer) and local ischemic postconditioning (IPost) are promising methods to decrease ischemia-reperfusion injury. We tested whether these two methods were effective in reducing infarct size through activation of endoplasmic reticulum (ER) stress response, a potential survival pathway. Rats exposed to myocardial ischemia-reperfusion were allocated to one of six groups: control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated during coronary artery occlusion; control + 4-PBA, injection of ER stress inhibitor 4-phenylbutyrate (4-PBA) 1 h before coronary occlusion; IPost + 4-PBA; and RIPer + 4-PBA.

Microparticle release in remote ischemic conditioning mechanism.

Remote ischemic conditioning (RCond) induced by short periods of ischemia and reperfusion of an organ or tissue before myocardial reperfusion is an attractive strategy of cardioprotection in the context of acute myocardial infarction. Nonetheless, its mechanism remains unknown. A humoral factor appears to be involved, although its identity is currently unknown.

RISK and SAFE signaling pathway interactions in remote limb ischemic perconditioning in combination with local ischemic postconditioning.

Local ischemic postconditioning (IPost) and remote ischemic perconditioning (RIPer) are promising methods to decrease ischemia-reperfusion (I/R) injury. We tested whether the use of the two procedures in combination led to an improvement in cardioprotection through a higher activation of survival signaling pathways. Rats exposed to myocardial I/R were allocated to one of the following four groups: Control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated 20 min after coronary artery occlusion; IPost+RIPer, IPost and RIPer in combination.

Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling.

Recent studies reported cardioprotective effects of erythropoietin (EPO) against ischemia-reperfusion (I/R) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been reported to be impaired in diabetes and insulin resistance syndrome, we examined whether EPO-induced cardioprotection was maintained in rat models of type 1 diabetes and insulin resistance syndrome. Isolated hearts were obtained from three rat cohorts: healthy controls, streptozotocin (STZ)-induced diabetes, and high-fat diet (HFD)-induced insulin resistance syndrome.

Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats.

A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion.

Myocardial reperfusion injury management: erythropoietin compared with postconditioning.

Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study.

Left ventricular unloading with intra-aortic counter pulsation prior to reperfusion reduces myocardial release of endothelin-1 and decreases infarction size in a porcine ischemia-reperfusion model.

Objectives: We tested the hypothesis that unloading the left ventricle with intra-aortic balloon counter-pulsation just prior to reperfusion provides infarct salvage compared with left ventricular (LV) unloading postreperfusion or reperfusion alone.

Background: Previous reports demonstrated infarct salvage with complete LV unloading with an LVAD prior to reperfusion; however, partial LV unloading using intra-aortic balloon pumps (IABPs) has not been evaluated.

Methods: Twenty-eight Yorkshire pigs were subjected to 1 hr of left anterior descending artery occlusion and 4 hr of reperfusion.