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Journal of Cardiovascular Pharmacology... Jul 2018p53 is well known as a regulator of apoptosis and autophagy. In addition, a recent study showed that p53 is a modulator of the opening of the mitochondrial permeability...
p53 is well known as a regulator of apoptosis and autophagy. In addition, a recent study showed that p53 is a modulator of the opening of the mitochondrial permeability transition pore (mPTP), a trigger event of necrosis, but the role of p53 in necrosis induced by myocardial ischemia-reperfusion (I/R) remains unclear. The aim of this study was to determine the role of p53 in acute myocardial I/R injury in perfused mouse hearts. In male C57BL6 mice between 12 and 15 weeks of age, 2 types of p53 inhibitors were used to suppress p53 function during I/R: pifithrin-α, an inhibitor of transcriptional functions of p53, and pifithrin-μ, an inhibitor of p53 translocation from the cytosol to mitochondria. Neither infusion of these inhibitors before ischemia nor infusion for the first 30-minute period of reperfusion reduced infarct size after 20-minute ischemia/120-minute reperfusion. Infarct sizes were similar in p53 heterozygous knockout mice (p53) and wild-type mice (WT), but recovery of rate pressure product (RRP) 120 minutes after reperfusion was higher in p53 than in WT. The protein expression of p53 in WT was negligible under baseline conditions, during ischemia, and at 10 minutes after the start of reperfusion, but it became detectable at 120 minutes after reperfusion. In conclusion, upregulation of p53 during the late phase of reperfusion plays a significant role in contractile dysfunction after reperfusion, although p53 is not involved in cardiomyocyte necrosis during ischemia or in the early phase of reperfusion.
Topics: Animals; Benzothiazoles; Disease Models, Animal; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Necrosis; Sulfonamides; Time Factors; Toluene; Tumor Suppressor Protein p53; Ventricular Function, Left
PubMed: 29554809
DOI: 10.1177/1074248418763612 -
Arquivos Brasileiros de Cardiologia Mar 2022About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy.
BACKGROUND
About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy.
OBJECTIVE
The use of a telemedicine network based on WhatsApp® could increase the percentage of patients receiving reperfusion therapy.
METHODS
A cross-sectional study analyzed outcomes before and after the organization of a telemedicine network to send the electrocardiogram via WhatsApp® of patients suspected of STEMI from 25 municipalities that are members of the Regional Health Department of Ribeirão Preto (DRS-XIII) to a tertiary hospital, which could authorize immediate patient transfer using the same system. The analyzed outcomes included the percentage of patients who received reperfusion therapy and the in-hospital mortality rate. A p value < 0.05 was considered statistically significant.
RESULTS
The study compared 82 patients before (February 1, 2016 to January 31, 2018) with 196 patients after this network implementation (February 1, 2018 to January 31, 2020). After implementing this network, there was a significant increase in the proportion of patients who received reperfusion therapy (60% vs. 92%), relative risk (RR): 1.594 [95% confidence interval (CI) 1.331 - 1.909], p < 0.0001 and decrease in the in-hospital mortality rate (13.4% vs. 5.6%), RR: 0.418 [95%CI 0.189 - 0.927], p = 0.028.
CONCLUSION
The use of WhatsApp®-based telemedicine has led to an increase in the percentage of patients with STEMI who received reperfusion therapy and a decrease in the in-hospital mortality rate.
Topics: Cross-Sectional Studies; Electrocardiography; Hospital Mortality; Humans; Myocardial Infarction; Myocardial Reperfusion; ST Elevation Myocardial Infarction; Telemedicine
PubMed: 35137785
DOI: 10.36660/abc.20201243 -
Circulation. Cardiovascular... Nov 2022
Topics: Humans; Treatment Outcome; ST Elevation Myocardial Infarction; Myocardial Reperfusion; Percutaneous Coronary Intervention; Electrocardiography
PubMed: 36305317
DOI: 10.1161/CIRCINTERVENTIONS.122.012528 -
Journal of the American College of... Jul 2019After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and... (Review)
Review
After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes.
Topics: Biomedical Research; Cardiac Imaging Techniques; Clinical Trials as Topic; Heart; Humans; Magnetic Resonance Imaging; Myocardial Infarction; Myocardial Reperfusion; Postoperative Period
PubMed: 31296297
DOI: 10.1016/j.jacc.2019.05.024 -
Medical Science Monitor : International... Jun 2020Early reperfusion remains the key therapy to salvage viable myocardium and must be applied as soon as possible following an acute myocardial infarction (AMI) to... (Review)
Review
Early reperfusion remains the key therapy to salvage viable myocardium and must be applied as soon as possible following an acute myocardial infarction (AMI) to attenuate the ischemic insult. However, reperfusion injury may develop following reintroduction of blood and oxygen to vulnerable myocytes, which results in more severe cell death than in the preceding ischemic episode. Ischemic postconditioning (I-PostC) provides a cardioprotective effect in combination with pharmacological agents. Although nitrates have been tested in many experimental and clinical studies of acute AMI to evaluate the cardioprotective effect, few investigations have been focused on nitrates postconditioning in patients undergoing percutaneous coronary intervention (PCI). This review presents the manifestations of myocardial reperfusion injury (RI) and potential mechanisms underlying it, and provides the mechanisms involved in the cardioprotection of I-PostC. We also present a new therapeutic approach to attenuate RI by use of an 'old' agent - nitrates - in AMI patients.
Topics: Animals; Humans; Ischemia; Ischemic Postconditioning; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Nitrates; Percutaneous Coronary Intervention
PubMed: 32516304
DOI: 10.12659/MSM.923129 -
Human & Experimental Toxicology 2022Bone marrow mesenchymal stem cells (BMMSCs) exert protective effects against myocardial infarction (MI). Here, we focused on the function and mechanism of miR-455-3p...
OBJECTIVE
Bone marrow mesenchymal stem cells (BMMSCs) exert protective effects against myocardial infarction (MI). Here, we focused on the function and mechanism of miR-455-3p from BMMSCs-derived exosomes (BMMSCs-Exo) in myocardial infarction.
MATERIALS AND METHODS
BMMSCs were isolated from rat bone marrow, and the exosomes from the culture medium of BMMSCs were separated, and administered to H9C2 cells under hypoxia-reperfusion (H/R) stimulation. MTT and TUNEL staining analyzed cell viability and apoptosis, respectively. RT-qPCR determined miR-455-3p expression. Apoptosis-related proteins, autophagy-associated proteins, and the MEKK1-MKK4-JNK signaling pathway were detected. The interaction between miR-455-3p and MEKK1 was confirmed through dual luciferase activity and RIP assay. An in vivo ischemia reperfusion (I/R) model was established in rats. 2, 3, 5 triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, Masson staining, and TUNEL staining evaluated the infarct volume and histopathological changes.
RESULTS
miR-455-3p's expression was down-regulated in BMMSCs-derived exosomes, I/R myocardial tissues, and H/R myocardial cells. miR-455-3p enriched by BMMSC exosomes reduced H/R-mediated cardiomyocyte damage and death-related autophagy. miR-455-3p upregulation suppressed MEKK1-MKK4-JNK. MEKK1 overexpression notably mitigated cell apoptosis, cramped cell viability, suppressed autophagy expansion, and attenuated Exo-miR-455-3p's protection on H/R myocardial cells. trials reflected that BMMSC exosomes enriched with miR-455-3p repressed ischemia reperfusion-induced myocardial damage and myocardial cell function.
CONCLUSION
miR-455-3p, shuttled by exosomes from MSCs, targets the MEKK1-MKK4-JNK signaling pathway to guard against myocardial ischemia-reperfusion damage.
Topics: Animals; Apoptosis; Exosomes; Mesenchymal Stem Cells; MicroRNAs; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats
PubMed: 35577544
DOI: 10.1177/09603271221102508 -
Journal of Women's Health (2002) Nov 2015
Topics: Female; Health Services Accessibility; Hospital Mortality; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Sex Factors
PubMed: 26288193
DOI: 10.1089/jwh.2015.5412 -
Frontiers in Immunology 2018Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in modern medicine. Early reperfusion accomplished by primary percutaneous coronary... (Review)
Review
The Lectin Pathway of Complement in Myocardial Ischemia/Reperfusion Injury-Review of Its Significance and the Potential Impact of Therapeutic Interference by C1 Esterase Inhibitor.
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in modern medicine. Early reperfusion accomplished by primary percutaneous coronary intervention is pivotal for reducing myocardial damage in ST elevation AMI. However, restoration of coronary blood flow may paradoxically trigger cardiomyocyte death secondary to a reperfusion-induced inflammatory process, which may account for a significant proportion of the final infarct size. Unfortunately, recent human trials targeting myocardial ischemia/reperfusion (I/R) injury have yielded disappointing results. In experimental models of myocardial I/R injury, the complement system, and in particular the lectin pathway, have been identified as major contributors. In line with this, C1 esterase inhibitor (C1INH), the natural inhibitor of the lectin pathway, was shown to significantly ameliorate myocardial I/R injury. However, the hypothesis of a considerable augmentation of myocardial I/R injury by activation of the lectin pathway has not yet been confirmed in humans, which questions the efficacy of a therapeutic strategy solely aimed at the inhibition of the lectin pathway after human AMI. Thus, as C1INH is a multiple-action inhibitor targeting several pathways and mediators simultaneously in addition to the lectin pathway, such as the contact and coagulation system and tissue leukocyte infiltration, this may be considered as being advantageous over exclusive inhibition of the lectin pathway. In this review, we summarize current concepts and evidence addressing the role of the lectin pathway as a potent mediator/modulator of myocardial I/R injury in animal models and in patients. In addition, we focus on the evidence and the potential advantages of using the natural inhibitor of the lectin pathway, C1INH, as a future therapeutic approach in AMI given its ability to interfere with several plasmatic cascades. Ameliorating myocardial I/R injury by targeting the complement system and other plasmatic cascades remains a valid option for future therapeutic interventions.
Topics: Animals; Biomarkers; Complement C1 Inhibitor Protein; Complement Pathway, Mannose-Binding Lectin; Humans; Molecular Targeted Therapy; Myocardial Reperfusion Injury; Treatment Outcome
PubMed: 29910807
DOI: 10.3389/fimmu.2018.01151 -
Basic Research in Cardiology Mar 2016Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in... (Review)
Review
Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in experimental models of ischemia/reperfusion and in humans undergoing reperfusion therapy for AMI have examined potential beneficial effects of nitric oxide (NO) supplemented at the time of reperfusion. Using a rigorous systematic search approach, we have identified and critically evaluated all the relevant experimental and clinical literature to assess whether exogenous NO given at reperfusion can limit infarct size. An inclusive search strategy was undertaken to identify all in vivo experimental animal and clinical human studies published in the period 1990-2014 where NO gas, nitrite, nitrate or NO donors were given to ameliorate reperfusion injury. Articles were screened at title and subsequently at abstract level, followed by objective full text analysis using a critical appraisal tool. In twenty-one animal studies, all NO treatments except nitroglycerin afforded protection against measures of reperfusion injury, including infarct size, creatinine kinase release, neutrophil accumulation and cardiac dysfunction. In three human AMI RCT's, there was no consistent evidence of infarct limitation associated with NO treatment as an adjunct to reperfusion. Despite experimental evidence that most NO treatments can reduce infarct size when given as adjuncts to reperfusion, the value of these interventions in clinical AMI is unproven. Our study raises issues for the design of further clinical studies and emphasises the need for improved design of animal studies to reflect more accurately the comorbidities and other confounding factors seen in clinical AMI.
Topics: Animals; Humans; Myocardial Infarction; Myocardial Reperfusion; Nitric Oxide
PubMed: 26912064
DOI: 10.1007/s00395-016-0540-y -
Hellenic Journal of Cardiology : HJC =... 2018
Comparative Study
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Cardiovascular Agents; Cyclopropanes; Disease Models, Animal; Humans; Ischemic Preconditioning, Myocardial; Metoprolol; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Protein Kinase Inhibitors; Pyridines; Ventricular Dysfunction, Left
PubMed: 30448621
DOI: 10.1016/j.hjc.2018.11.002