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Basic Research in Cardiology Jan 2018Research on cardioprotection has attracted considerable attention during the past 30 years following the discovery of ischemic preconditioning with great advances being... (Review)
Review
Research on cardioprotection has attracted considerable attention during the past 30 years following the discovery of ischemic preconditioning with great advances being made in the field, particularly in the description of the molecular signalling behind this cardioprotective intervention. In a time when basic research is struggling to translate its findings into therapies in the clinical setting, this viewpoint has the intention of presenting to clinical and basic scientists how the reperfusion injury salvage kinase pathway has been described and dissected, as well as highlighting its relevance in cardioprotection.
Topics: Animals; Apoptosis; Humans; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Phosphotransferases
PubMed: 29143177
DOI: 10.1007/s00395-017-0662-x -
Circulation Research Jun 2015The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to... (Review)
Review
The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and prevention of reperfusion injury, as this holds the promise of restoring life to many patients for whom our current therapies fail.
Topics: Calcium Signaling; Cardiopulmonary Resuscitation; Cardiovascular Agents; Chest Wall Oscillation; Combined Modality Therapy; Defibrillators; Defibrillators, Implantable; Drug Therapy, Combination; Electric Countershock; Equipment Design; Heart Arrest; Humans; Mitochondria, Heart; Models, Cardiovascular; Myocardial Contraction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Survival Rate; Treatment Outcome; Ventricular Fibrillation
PubMed: 26044255
DOI: 10.1161/CIRCRESAHA.116.304495 -
Journal of Cardiovascular Pharmacology... Nov 2021Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous... (Review)
Review
Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous cardioprotection protocols and therapies have been pursued with success in pre-clinical models. Unfortunately, there has been lack of successful large-scale clinical translation, perhaps in part due to the multiple pathways that reperfusion can contribute to cell death. The search continues for new cardioprotection protocols based on what has been learned from past results. One class of cardioprotection protocols that remain under active investigation is that of controlled reperfusion. This class consists of those approaches that modify, in a controlled manner, the content of the reperfusate or the mechanical properties of the reperfusate (e.g., pressure and flow). This review article first provides a basic overview of the primary pathways to cell death that have the potential to be addressed by various forms of controlled reperfusion, including no-reflow phenomenon, ion imbalances (particularly calcium overload), and oxidative stress. Descriptions of various controlled reperfusion approaches are described, along with summaries of both mechanistic and outcome-oriented studies at the pre-clinical and clinical phases. This review will constrain itself to approaches that modify endogenously-occurring blood components. These approaches include ischemic postconditioning, gentle reperfusion, controlled hypoxic reperfusion, controlled hyperoxic reperfusion, controlled acidotic reperfusion, and controlled ionic reperfusion. This review concludes with a discussion of the limitations of past approaches and how they point to potential directions of investigation for the future.
Topics: Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Oxidative Stress
PubMed: 34534022
DOI: 10.1177/10742484211046674 -
Basic Research in Cardiology Jan 2023Following an acute myocardial infarction, reperfusion of an occluded coronary artery is often accompanied by microvascular injury, leading to worse long-term prognosis....
Following an acute myocardial infarction, reperfusion of an occluded coronary artery is often accompanied by microvascular injury, leading to worse long-term prognosis. Experimental studies have revealed the potential of tyrosine-kinase inhibitor imatinib to reduce vascular leakage in various organs. Here, we examined the potential of imatinib to attenuate microvascular injury in a rat model of myocardial reperfusion injury. Isolated male Wistar rat hearts (n = 20) in a Langendorff system and male Wistar rats (n = 37) in an in vivo model were randomly assigned to imatinib or placebo and subjected to ischaemia and reperfusion. Evans-blue/Thioflavin-S/TTC staining and Cardiac Magnetic Resonance Imaging were performed to assess the extent of reperfusion injury. Subsequently, in vivo hearts were perfused ex vivo with a vascular leakage tracer and fluorescence and electron microscopy were performed. In isolated rat hearts, imatinib reduced global infarct size, improved end-diastolic pressure, and improved rate pressure product recovery compared to placebo. In vivo, imatinib reduced no-reflow and infarct size with no difference between imatinib and placebo for global cardiac function. In addition, imatinib showed lower vascular resistance, higher coronary flow, and less microvascular leakage in the affected myocardium. At the ultrastructural level, imatinib showed higher preserved microvascular integrity compared to placebo. We provide evidence that low-dose imatinib can reduce microvascular injury and accompanying myocardial infarct size in a rat model of acute myocardial infarction. These data warrant future work to examine the potential of imatinib to reduce reperfusion injury in patients with acute myocardial infarction.
Topics: Rats; Male; Animals; Imatinib Mesylate; Rats, Wistar; Myocardial Infarction; Heart; Myocardium; Myocardial Reperfusion Injury; Myocardial Reperfusion
PubMed: 36639597
DOI: 10.1007/s00395-022-00974-z -
International Journal of Molecular... Mar 2022Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as... (Review)
Review
Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia-reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.
Topics: Humans; MicroRNAs; Myocardial Infarction; Myocardial Reperfusion Injury; Nucleotides; RNA, Long Noncoding; RNA, Untranslated
PubMed: 35269870
DOI: 10.3390/ijms23052728 -
Heart (British Cardiac Society) Mar 2016Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation... (Review)
Review
Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is 'myocardial reperfusion injury', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury.
Topics: Animals; Cardiovascular Agents; Heart Failure; Humans; Ischemic Postconditioning; Ischemic Preconditioning; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Percutaneous Coronary Intervention; Risk Factors; Treatment Outcome
PubMed: 26674987
DOI: 10.1136/heartjnl-2015-307855 -
American Journal of Physiology. Heart... Jul 2021There is a lack of understanding in the cardiac remodeling field regarding the use of nonreperfused myocardial infarction (MI) and reperfused MI in animal models of MI....
There is a lack of understanding in the cardiac remodeling field regarding the use of nonreperfused myocardial infarction (MI) and reperfused MI in animal models of MI. This Perspectives summarizes the consensus of the authors regarding how to select the optimum model for your experiments and is a part of ongoing efforts to establish rigor and reproducibility in cardiac physiology research.
Topics: Animals; Disease Models, Animal; Heart; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion
PubMed: 34114891
DOI: 10.1152/ajpheart.00234.2021 -
Kardiologia Polska Oct 2019Little attention is paid to the coronary microvasculature when treating acute myocardial infarction (MI). Microvascular obstruction (MVO) contributes to... (Review)
Review
Little attention is paid to the coronary microvasculature when treating acute myocardial infarction (MI). Microvascular obstruction (MVO) contributes to ischemia-reperfusion injury, which hampers distal blood flow to the myocardium despite recanalization of the culprit epicardial vessel. One of the mechanisms behind reperfusion injury is MVO due to persistent vasoconstrictor tone during reperfusion. Arginine vasopressin (AVP) is a hormone with prominent vasoactive effects on the coronary microvessels. Its levels are elevated as part of a stress response triggered by MI, which was shown to exert vasoconstrictive effects on the coronary arteries in preclinical models, mainly in the nonepicardial vessels of the microcirculation. Circulating AVP levels are up to 100‑fold higher in MI and do not immediately decrease to baseline levels on reperfusion. This results in the so called coronary slow flow phenomenon and mediates ischemia-reperfusion injury. Recently, the C‑terminal fragment of preprovasopressin, copeptin, has emerged as a surrogate biomarker for AVP, as it is more stable in the circulation. Multiple studies have shown the predictive value of both AVP and copeptin with regards to long‑term prognoses of MI patients. We propose that both AVP and copeptin have more than just a predictive value but also play a role in the pathophysiology of adverse outcome post‑MI. Therefore, the treatment of choice for MI should not only focus on the epicardial vessel but also on targeting MVO that might pre‑exist or might directly follow reperfusion. This mandates a clinical trial with an AVP‑receptor antagonist in patients with acute MI undergoing reperfusion therapy.
Topics: Animals; Arginine Vasopressin; Humans; Myocardial Infarction; Myocardial Reperfusion
PubMed: 31553327
DOI: 10.33963/KP.14986 -
Anaesthesia May 2015Ischaemic heart disease remains the leading cause of death worldwide. Novel approaches to improve morbidity and mortality in this population are essential. Cardiac... (Review)
Review
Ischaemic heart disease remains the leading cause of death worldwide. Novel approaches to improve morbidity and mortality in this population are essential. Cardiac ischaemic postconditioning - the technique of applying alternating cycles of sublethal myocardial ischaemia and reperfusion after a sustained insult - is one cardioprotective strategy that can reduce reperfusion injury. Infarct size reduction and improvements in left ventricular ejection fraction have been demonstrated with mechanical or pharmacological postconditioning, both after spontaneous acute myocardial infarction, and associated with cardiac surgery. Nonetheless, the benefits of postconditioning can be easily attenuated. For maximal benefit, postconditioning demands a particular patient population (large area at risk, with little collateral blood flow), timely application and the measurement of appropriate clinical endpoints. Furthermore, confounders such age, sex and medication, as well as a plethora of co-morbidities common in patients with ischaemic heart disease, all impact on the efficacy of postconditioning. This fragility requires the security of outcomes from large-scale human trials to ensure robust applicability to everyday clinical practice, and to provide assurance of an impact on long-term clinical outcome. This review highlights the development of current postconditioning algorithms, the findings from current proof-of-concept trials, and the barriers that may limit its broad uptake into clinical practice.
Topics: Cardiac Surgical Procedures; Heart Diseases; Humans; Ischemic Postconditioning; Myocardial Ischemia; Myocardial Reperfusion
PubMed: 25682886
DOI: 10.1111/anae.12974 -
Biomedicine & Pharmacotherapy =... May 2022Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction.... (Review)
Review
Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria.
Topics: Biological Products; Humans; Mitochondria; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Reactive Oxygen Species; Reperfusion
PubMed: 35366532
DOI: 10.1016/j.biopha.2022.112893