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ARYA Atherosclerosis 2023The generation of reactive oxygen species, which is induced by the activation of the xanthine oxidase (XO) enzymatic system, is one of the primary causes of...
Impact of Allopurinol Pretreatment on Coronary Blood Flow and Revascularization Outcomes after Percutaneous Coronary Intervention in Acute STEMI Patients: A Randomized Double Blind Clinical Trial.
INTRODUCTION
The generation of reactive oxygen species, which is induced by the activation of the xanthine oxidase (XO) enzymatic system, is one of the primary causes of ischemia-reperfusion injury for an ischemic heart. Allopurinol, as an XO inhibitor, plays an inhibitory role in free radical production in ST-elevation myocardial infarction (STEMI) patients. The aim of this study is to evaluate the impact of allopurinol pre-treatment on post-revascularization outcomes in patients admitted with STEMI.
METHOD
Ninety patients with acute STEMI were enrolled in this randomized double-blind clinical trial and divided into two equal groups. The allopurinol group received a 600 mg allopurinol loading dose before the emergency PCI, and the control group received a placebo medication of the same shape. Thrombolysis in Myocardial Infarction (TIMI) flow, ECG changes, troponin level, and the occurrence of major cardiac events (MACE) during a 1-month follow-up were assessed.
RESULTS
In the end, 81 patients were analyzed. The mean age of the patients was 59.52(11.31) and 61.3(9.25) in the allopurinol and control groups, respectively (p = 0.49). The troponin level 48 hours after the PCI and ST-elevation regression showed no significant difference between the groups [(p = 0.25) and (p = 0.21), respectively]. TIMI flow had improved in the allopurinol group compared to the placebo (p = 0.02). The PCI success rate was 78.6% and 61.5% in the case and control groups, respectively (p = 0.09). MACE and other clinical outcomes were similar between the groups (p > 0.05).
CONCLUSION
This study revealed that allopurinol pre-treatment could improve TIMI flow in patients undergoing primary or rescue PCI in an acute STEMI setting.
PubMed: 38883850
DOI: 10.48305/arya.2023.11577.2121 -
Zhonghua Xin Xue Guan Bing Za Zhi Jun 2024
Review
Topics: Myocardial Reperfusion Injury; Antioxidants; Humans; Oxidative Stress; Nanoparticles; Animals
PubMed: 38880758
DOI: 10.3760/cma.j.cn112148-20231008-00234 -
Biochemistry. Biokhimiia May 2024Ischemia/reperfusion (I/R) injury is one of the major causes of cardiovascular disease. Gypenoside A (GP), the main active component of Gynostemma pentaphyllum,...
Ischemia/reperfusion (I/R) injury is one of the major causes of cardiovascular disease. Gypenoside A (GP), the main active component of Gynostemma pentaphyllum, alleviates myocardial I/R injury. Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in the I/R injury. We explored the protective effect of GP on human cardiomyocytes (HCMs) via the circ_0010729/miR-370-3p/RUNX1 axis. Overexpression of circ_0010729 abolished the effects of GP on HMC, such as suppression of apoptosis and increase in cell viability and proliferation. Overexpression of miR-370-3p reversed the effect of circ_0010729 overexpression, resulting in the stimulation of HMC viability and proliferation and inhibition of apoptosis. The knockdown of miR-370-3p suppressed the effects of GP in HCMs. RUNX1 silencing counteracted the effect of miR-370-3p knockdown and maintained GP-induced suppression of apoptosis and stimulation of HMC viability and proliferation. The levels of RUNX1 mRNA and protein were reduced in cells expressing miR-370-3p. In conclusion, this study confirmed that GP alleviated the I/R injury of myocardial cell via the circ_0010729/miR-370-3p/RUNX1 axis.
Topics: Humans; MicroRNAs; RNA, Circular; Gynostemma; Core Binding Factor Alpha 2 Subunit; Myocardial Reperfusion Injury; Myocytes, Cardiac; Apoptosis; Cell Survival; Cell Proliferation; Plant Extracts
PubMed: 38880656
DOI: 10.1134/S000629792405016X -
Scientific Reports Jun 2024Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut...
Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia-reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was - 5.44, and the MM-GBSA result of - 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.
Topics: Animals; Ferroptosis; Gastrointestinal Microbiome; Male; Myocardial Reperfusion Injury; Benzhydryl Compounds; Methylamines; Rats; Glucosides; Rats, Sprague-Dawley; Molecular Docking Simulation; Diabetes Mellitus, Experimental
PubMed: 38879701
DOI: 10.1038/s41598-024-64909-5 -
Cell Death Discovery Jun 2024Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue... (Review)
Review
Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.
PubMed: 38879568
DOI: 10.1038/s41420-024-02064-6 -
Biomedicine & Pharmacotherapy =... Jul 2024Myocardial reperfusion injury occurs when blood flow is restored after ischemia, an essential process to salvage ischemic tissue. However, this phenomenon is intricate,... (Review)
Review
Myocardial reperfusion injury occurs when blood flow is restored after ischemia, an essential process to salvage ischemic tissue. However, this phenomenon is intricate, characterized by various harmful effects. Tissue damage in ischemia-reperfusion injury arises from various factors, including the production of reactive oxygen species, the sequestration of proinflammatory immune cells in ischemic tissues, the induction of endoplasmic reticulum stress, and the occurrence of postischemic capillary no-reflow. Secretory phospholipase A2 (sPLA2) plays a crucial role in the eicosanoid pathway by releasing free arachidonic acid from membrane phospholipids' sn-2 position. This liberated arachidonic acid serves as a substrate for various eicosanoid biosynthetic enzymes, including cyclooxygenases, lipoxygenases, and cytochromes P450, ultimately resulting in inflammation and an elevated risk of reperfusion injury. Therefore, the activation of sPLA2 directly correlates with the heightened and accelerated damage observed in myocardial ischemia-reperfusion injury (MIRI). Presently, clinical trials are in progress for medications aimed at sPLA2, presenting promising avenues for intervention. Cardiolipin (CL) plays a crucial role in maintaining mitochondrial function, and its alteration is closely linked to mitochondrial dysfunction observed in MIRI. This paper provides a critical analysis of CL modifications concerning mitochondrial dysfunction in MIRI, along with its associated molecular mechanisms. Additionally, it delves into various pharmacological approaches to prevent or alleviate MIRI, whether by directly targeting mitochondrial CL or through indirect means.
Topics: Humans; Myocardial Reperfusion Injury; Animals; Cardiolipins; Phospholipases A2, Secretory
PubMed: 38878685
DOI: 10.1016/j.biopha.2024.116936 -
Tissue & Cell Jun 2024Myocardial ischemia-reperfusion (MI/R) occurs due to temporary or permanent interruptions in the coronary and circulatory system, indirectly affecting kidney function...
Investigating the indirect therapeutic effect of hAMSCs utilizing a novel scaffold (PGS-co-PCL/PGC/PPy/Gelatin) in myocardial ischemia-reperfusion-induced renal failure in male Wistar rats.
BACKGROUND
Myocardial ischemia-reperfusion (MI/R) occurs due to temporary or permanent interruptions in the coronary and circulatory system, indirectly affecting kidney function through reduced cardiac output for metabolic needs. In this study, the aim was to explore the indirect effects of using human amniotic membrane mesenchymal stem cells (hAMSCs) with the PGS-co-PCL/PGC/PPy/Gelatin scaffold in male rats with renal failure induced by miocardial ischemia-reperfusion.
METHODS
MI/R injury was induced in 48 male Wistar rats through left anterior descending artery ligation, divided into four groups (n=12); control group, cell group, scaffold group, and celss+scaffold group. Evaluations were conducted at two and thirty days post MI/R injury, encompassing echocardiography, biochemical, inflammatory markers analysis, and histological assessment.
RESULTS
Echocardiographic findings exhibited notable enhancement in ejection fraction, fractional shortening, and stroke volume of treated groups compared to controls after 30 days (P< 0.05). Serum creatinine (P< 0.001) and urea (P< 0.05) levels significantly decreased in the scaffold+cells group) compared to the control group. The treated cells+ scaffold group displayed improved kidney structure, evidenced by larger glomeruli and reduced Bowman's space compared to the control group (P< 0.01). Immunohistochemical analysis indicated reduced TNF-α protein in the scaffold+ cells group (P< 0.05) in contrast to the control group (P< 0.05). Inflammatory factors IL-6, TNF-α, and AKT gene expression in renal tissues were improved in scaffold+ cells-treated animals.
CONCLUSION
Our research proposes the combination of hAMSCs and the PGS-co-PCL/PGC/PPy/Gelatin scaffold in MI/R injured rats appears to enhance renal function and reduce kidney inflammation by improving cardiac output.
PubMed: 38878657
DOI: 10.1016/j.tice.2024.102428 -
Basic Research in Cardiology Jun 2024Despite recent progress, ischemic heart disease poses a persistent global challenge, driving significant morbidity and mortality. The pursuit of therapeutic solutions... (Review)
Review
Despite recent progress, ischemic heart disease poses a persistent global challenge, driving significant morbidity and mortality. The pursuit of therapeutic solutions has led to the emergence of strategies such as ischemic preconditioning, postconditioning, and remote conditioning to shield the heart from myocardial ischemia/reperfusion injury (MIRI). These ischemic conditioning approaches, applied before, after, or at a distance from the affected organ, inspire future therapeutic strategies, including pharmacological conditioning. Gasotransmitters, comprising nitric oxide, hydrogen sulfide, sulfur dioxide, and carbon monoxide, play pivotal roles in physiological and pathological processes, exhibiting shared features such as smooth muscle relaxation, antiapoptotic effects, and anti-inflammatory properties. Despite potential risks at high concentrations, physiological levels of gasotransmitters induce vasorelaxation and promote cardioprotective effects. Noble gases, notably argon, helium, and xenon, exhibit organ-protective properties by reducing cell death, minimizing infarct size, and enhancing functional recovery in post-ischemic organs. The protective role of noble gases appears to hinge on their modulation of molecular pathways governing cell survival, leading to both pro- and antiapoptotic effects. Among noble gases, helium and xenon emerge as particularly promising in the field of cardioprotection. This overview synthesizes our current understanding of the roles played by gasotransmitters and noble gases in the context of MIRI and cardioprotection. In addition, we underscore potential future developments involving the utilization of noble gases and gasotransmitter donor molecules in advancing cardioprotective strategies.
PubMed: 38878210
DOI: 10.1007/s00395-024-01061-1 -
Applied Biochemistry and Biotechnology Jun 2024Although it is crucial to promptly restore blood perfusion to revive the ischemic myocardium, reperfusion itself can paradoxically contribute to the electrical...
Although it is crucial to promptly restore blood perfusion to revive the ischemic myocardium, reperfusion itself can paradoxically contribute to the electrical instability and arrhythmias of the myocardium. Several studies have revealed that cardiac fibroblasts can impact cardiac electrophysiology through various mechanisms including the deposition of extracellular matrix, release of chemical mediators, and direct electrical coupling with myocytes. Previously, we have shown that hypoxia/reoxygenation (H/R)-treated rat fibroblasts conditional medium (H/R-FCM) could decrease the spontaneous beating frequency of rat neonatal cardiomyocytes and downregulate the expression of gap junction proteins. However, the specific mechanism by which H/R-FCM affects the gap junctions requires further investigation. H/R-FCM was obtained by culturing confluent rat cardiac fibroblasts (RCF) for 4 h under hypoxic conditions. Gap junction function, hemichannel activity, and expression of Cx43 were examined upon treatment with H/R-FCM. Gelatin zymography was performed to detect matrix metalloproteinase (MMP) activity in the conditioned medium. The effect of H/R-FCM and MMP2 inhibitors on cardiac electrophysiology and arrhythmias was investigated with an isolated rat ischemia/reperfusion (I/R) model. H/R-FCM treatment impaired gap junction function, downregulated Cx43 expression, and increased hemichannel activity in rat cardiomyocytes (H9c2). The adverse effect of H/R-FCM on gap junction, which was confirmed by the cardiomyocyte H/R model, was involved in the activation of MMP2. MMP2 inhibition could partially attenuate the detrimental effects of I/R on myocardial electrophysiological indices and arrhythmia susceptibility. Our study indicates that inhibition of MMP2 may be a promising therapeutic target for the treatment of reperfusion arrhythmia.
PubMed: 38878160
DOI: 10.1007/s12010-024-04986-4 -
JACC. Heart Failure Jun 2024As a result of the widespread use of reperfusion therapies and secondary prevention over the last 30 years, there has been a dramatic reduction in the risk of mortality... (Review)
Review
As a result of the widespread use of reperfusion therapies and secondary prevention over the last 30 years, there has been a dramatic reduction in the risk of mortality and development of heart failure (HF) following acute myocardial infarction (MI). Despite this, the development of chronic HF remains a common occurrence in the days, months, and years following MI. Neurohormonal inhibition remains the mainstay of pharmacologic prevention of HF following MI, with recent trials showing an additive benefit of a neprilysin inhibitor or a sodium glucose co-transporter 2 inhibitor in reducing the risk of development of HF but no significant effect on mortality. Novel imaging tools may help refine risk stratification in high-risk patients and allow greater targeting of preventative therapies in patients most likely to benefit. Research is ongoing into novel therapies aiming to minimize the degree of myocardial damage and prevention of progressive adverse remodeling following MI.
PubMed: 38878010
DOI: 10.1016/j.jchf.2024.04.025