Materiały źródłowe

• #1 The pathophysiology of myocardial ischaemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1768241/

  Myocardial ischaemia is responsible for angina, unstable angina, and, less commonly, shortness of breath secondary to ischaemic left ventricular dysfunction (angina equivalent) as well as cardiac arrhythmias. This article will deal with the mechanisms of myocardial ischaemia likely to be encountered in patients presenting with the chronic coronary insufficiency and stable symptoms of angina. […] The undergraduate, see-saw diagram showing the perfect match between myocardial oxygen consumption (MVo2) and oxygen delivery to the myocardium remains at the core of our understanding of myocardial ischaemia. Changes in MVo2, because of their relation to symptomatology and the rather more tractable nature of this parameter experimentally, have been concentrated on as a mechanism explaining myocardial ischaemia. However, not only is it plausible that changes in oxygen delivery influence the process of myocardial ischaemia, but to explain the day to day symptoms of patients with angina, changes in both MVo2 and oxygen delivery together or separately must occur.

• #1 An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives

  https://www.mdpi.com/2073-4409/11/7/1165

  Conditions leading to myocardial ischemia in patients may occur both acutely and chronically. These conditions are characterized by a lack of balance between demand and supply of oxygen and nutrients to myocardial tissue. […] Acute myocardial ischemia usually involves the rapid reduction or arrest of coronary blood flow to the myocardium, which impairs cardiomyocyte function and survival, eventually leading to myocardial infarction (MI) if blood flow is not rapidly restored. […] The heart requires an extensive energy supply to maintain its function, which is provided by adenosine triphosphate (ATP), mainly produced through oxidative phosphorylation. Cardiomyocytes are strictly dependent on oxygen to meet their metabolic demands. An interruption of coronary blood flow rapidly stresses cardiomyocytes and ultimately leads to apoptosis and necrosis.

• #1 Angina Pectoris: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150215-overview

  Myocardial ischemia can result from (1) a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary artery (ie, conductive vessel) stenosis, (2) abnormal constriction or deficient relaxation of coronary microcirculation (ie, resistance vessels), or (3) reduced oxygen-carrying capacity of the blood. […] Atherosclerosis is the most common cause of epicardial coronary artery stenosis and, hence, angina pectoris. Patients with a fixed coronary atherosclerotic lesion of at least 50% show myocardial ischemia during increased myocardial metabolic demand as the result of a significant reduction in CFR. […] Fixed atherosclerotic lesions of at least 90% almost completely abolish the flow reserve; patients with these lesions may experience angina at rest. […] Coronary spasm can also reduce CFR significantly by causing dynamic stenosis of coronary arteries. Prinzmetal angina is defined as resting angina associated with ST-segment elevation caused by focal coronary artery spasm.

• #1 ISCHEMIC HEART DISEASE: General concepts – Pathology Made Simple

  https://ilovepathology.com/ischemic-heart-disease-general-concepts/

  Myocardial ischemia occurs when there is an imbalance between the oxygen supply (through blood perfusion) to the heart muscle and the hearts demand for oxygenated blood. […] The primary cause is obstruction of blood flow in the coronary arteries due to atherosclerosis. Over 90% of cases are attributed to atherosclerotic plaques in the epicardial coronary arteries. […] Progressive narrowing of coronary arteries due to atherosclerosis reduces blood supply, leading to myocardial ischemia. […] Acute plaque changes, such as rupture, fissure, ulceration, or hemorrhage within the plaque, can lead to sudden obstruction or occlusion of coronary arteries. […] When myocardial ischemia occurs, the lack of oxygen leads to: Reduced ATP production Decreased availability of nutrients Impaired removal of metabolic waste products This eventually causes cell injury, which manifests as chest pain, necrosis of cardiac tissue (infarction), or arrhythmias.

• #1 Myocardial Infarction: Risk Factors, Pathophysiology, Classification, Assessment and Management | Auctores

  https://www.auctoresonline.org/article/myocardial-infarction-risk-factors-pathophysiology-classification-assessment-and-management

  Coronary endothelial dysfunction precedes the lesion formation and increases with progression of CAD. It results from endothelial injury that occurs in response to oxidized LDL, increased levels of blood glucose, hypertension and increased free radicals derived from oxygen. […] Atherosclerosis is the main cause of plaque formation by causing internal inflammation, fibrosis, necrosis and calcification. […] The direct mechanism is through accumulation of LDLs in the arterial endothelium with an intrinsic adaptive thickening (Bentzon et al, 2014). […] Plaque rupture leads to exposure of blood with the necrotic core that is rich with erythrocytes and highly thrombogenic material leading to clot formation. Plaque rupture represents the most common cause for occurrence of thrombosis (Bentzon et al, 2014).

• #1 Angina Pectoris: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150215-overview

  Approximately 30% of patients with chest pain referred for cardiac catheterization have normal or minimal atherosclerosis of coronary arteries. A subset of these patients demonstrates reduced CFR that is believed to be caused by functional and structural alterations of small coronary arteries and arterioles (ie, resistance vessels). […] Angina due to dysfunction of small coronary arteries and arterioles is called microvascular angina. […] The syndrome that includes angina pectoris, ischemialike ST-segment changes and/or myocardial perfusion defects during stress testing, and angiographically normal coronary arteries is referred to as syndrome X. […] A number of extravascular forces produced by contraction of adjacent myocardium and intraventricular pressures can influence coronary microcirculation resistance and thus reduce CFR.

• #1 Cardiac Syndrome X and Myocardial Ischemia: Pathogenesis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4471-4838-8_7

  Cardiac syndrome X (CSX) is characterized by: (1) angina chest pain triggered by effort; (2) ST-segment depression on exercise stress electrocardiogram or other findings compatible with myocardial ischemia; (3) normal coronary arteries at angiography, in absence of any specific cardiac or systemic disease. Myocardial ischemia related to abnormalities in coronary microcirculation is in most cases responsible for the angina symptoms (microvascular angina, MVA). […] The mechanisms responsible for coronary microvascular dysfunction (CMVD) include both reduced coronary microvascular dilation and enhanced coronary microvascular constriction. Moreover, the impaired microvascular dilator function may involve both endothelium-independent and endothelium-dependent mechanisms. […] The causes responsible for CMVD in CSX are also heterogeneous. Traditional cardiovascular risk factors, including hypertension, dyslipidaemia, blood glucose disorders and smoking might play some role. Some conditions frequently found associated with CSX, however, include abnormal adrenergic nerve function, insulin resistance, inflammation and (in women) estrogen deficiency.

• #1 Angina Pectoris: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/150215-overview

  Myocardial ischemia can also be the result of factors affecting blood composition, such as reduced oxygen-carrying capacity of blood, as is observed with severe anemia (hemoglobin, 8 g/dL), or elevated levels of carboxyhemoglobin. […] Ambulatory ECG monitoring has shown that silent ischemia is a common phenomenon among patients with established coronary artery disease.

• #1 Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation, and Clinical Applications

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10399947/

  Myocardial ischemia is a major mechanism in the pathogenesis of cardiac dysfunction in a variety of clinical settings. […] In response to impaired coronary blood flow, myocardial ischemic injury is manifested as progressive alteration in function, metabolism, and structure of the affected myocardium. […] Reperfusion halts the progression of myocardial ischemic injury, salvages myocardium by restoration of blood flow, and simultaneously produces sublethal to lethal reperfusion injury in marginally viable myocardium. […] Myocardial ischemic injury is manifested by progressive alterations in high energy phosphate metabolism and electrolyte homeostasis. […] With the onset of myocardial ischemia, oxygen is rapidly depleted, causing mitochondrial respiration to cease, thereby reducing the availability of the high energy phosphate, adenosine triphosphate (ATP).

• #1 Myocardial Response To Ischemia – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/myocardial-response-to-ischemia

  Cocaine and vasospastic angina can cause coronary artery vasoconstriction, further decreasing the coronary oxygen supply. Diminished coronary oxygen supply can also arise from coronary embolism, dissection, arteritis, myocardial fibrosis, or in systemic hypoxia due to conditions like hypotension, shock, anemia, and carbon monoxide poisoning. […] In ischemic conditions, myocardial cells switch to anaerobic glycolysis within seconds, leading to ATP depletion and myofibril relaxation. […] However, after 30 minutes, the damage becomes irreversible and is indicated by signs like mitochondrial vacuolization, and myocyte cell membrane breakdown which leads to the release of troponin creatine kinase, indicating irreversible cell damage. […] Reperfusion injury can occur during the restoration of blood flow, leading to further cellular damage through the buildup of intracellular calcium during ischemia, which causes hypercontracture and cytoskeletal damage upon reperfusion.

• #1 Different types of cell death and their interactions in myocardial ischemia–reperfusion injury | Cell Death Discovery

  https://www.nature.com/articles/s41420-025-02372-5

  Myocardial ischemiareperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow is restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, is pivotal in myocardial I/R injury. Preventing cell death during the process of I/R is vital for improving ischemic cardiomyopathy. […] These multiple forms of cell death can occur simultaneously, interact with each other, and contribute to the complexity of myocardial I/R injury. […] It is important to note that manipulating the molecules or targets involved in distinct cell death processes may have a significant impact on reducing myocardial I/R injury. […] Myocardial I/R injury obtains complex pathogenesis, including oxidative stress, the opening of mitochondrial permeability transition pore (MPTP), and local inflammatory response.

• #1 Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review)

  https://www.spandidos-publications.com/10.3892/etm.2022.11357

  Numerous studies have researched mechanisms underlying MIRI; the pathophysiological mechanisms of MIRI are associated with oxidative stress, intracellular calcium overload, energy metabolism disorder, apoptosis, endoplasmic reticulum stress (ERS), autophagy, pyroptosis, ferroptosis and necroptosis. […] Oxidative stress induced by reperfusion after ischemia is considered to be the primary mechanism of IRI. […] The opening of mPTP may contribute to loss of ATP, mitochondrial swelling and CytC release, leading to apoptosis. […] Previous studies have indicated that apoptotic cell death is one of the primary forms of cardiomyocyte death during MIRI. […] IRI may be associated with ERS. […] During MIRI, ERS is increased and inhibition of ERS has been shown to attenuate MIRI. […] Autophagy, the primary function of which is to remove and recover misfolded or damaged proteins and organelles, is not only associated with cell survival but also with cell death.

• #1 Different types of cell death and their interactions in myocardial ischemia–reperfusion injury | Cell Death Discovery

  https://www.nature.com/articles/s41420-025-02372-5

  The loss of cardiomyocytes is a certainly outcome of reperfusion injury, which can occur through apoptosis, necroptosis, autophagy, and other pathways, contributing to irreversible damage and cardiac dysfunction. […] During I/R, different types of cell death occur in a specific sequence, accompanied by distinct dynamic changes. […] However, emerging evidence now indicates a significant crosstalk and intricate interplay among these cell death mechanisms, blurring their traditional boundaries. […] Recognizing these processes and their interplay is essential for the formulation of effective therapeutic approaches aimed at alleviating I/R injury. […] During the later reperfusion phase, necroptosis occurs. […] The process involves the production of massive amounts of inflammatory factors, such as TNF-, which activate RIPK1.

• #1 Myocardial Ischemia/Reperfusion Injury: Mechanism and Targeted Treatment for Ferroptosis The Anatolian Journal of Cardiology

  https://anatoljcardiol.com/article/AJC-00850

  Myocardial ischemia/reperfusion injury (MIRI) is a pathophysiological process connected to the onset of numerous heart disorders. The pathogenesis of MIRI is complex, and it mainly involves calcium overload, classic oxidative stress, mitochondrial disorder, inflammation, microvascular disorder, and cell death. […] Recent studies have demonstrated that ferroptosis is the main cause of MIRI. Ferroptosis is a new type of regulated iron-dependent cell death whose mechanism and targeted therapy are anticipated to be novel therapeutic techniques for MIRI. […] The pathological pathway of MIRI is complex and completely unclear but mainly includes calcium overload, oxidative stress, inflammatory response, mitochondrial permeability transition pore opening, energy metabolism disorders, and activation of different cell death modes.

• #1 Different types of cell death and their interactions in myocardial ischemia–reperfusion injury | Cell Death Discovery

  https://www.nature.com/articles/s41420-025-02372-5

  The phosphorylation of mixed lineage kinase domain-like protein (MLKL) also increased, indicating necroptosis. […] During reperfusion, oxidative stress intensifies, intracellular iron metabolism is disrupted, and the antioxidant defense system, such as glutathione peroxidase 4 (GPX4), is damaged. […] Ferroptosis may emerge during prolonged reperfusion when intracellular redox state imbalance and lipid metabolism abnormality reach a critical level. […] In brief, during I/R injury, these distinct types of cell death occur sequentially with unique dynamic characteristics, hinting at potential interactions among them. […] The intricate connections among these pathways reveal cross-regulation. […] The complex collaboration of different cell death pathways in myocardial I/R injury requires a clearer explanation. […] Exploring the mechanisms of cell death in myocardial I/R injury in order to uncover novel cardioprotective interventions.

• #1 Myocardial Ischemia/Reperfusion Injury: Mechanism and Targeted Treatment for Ferroptosis The Anatolian Journal of Cardiology

  https://anatoljcardiol.com/article/AJC-00850

  Studies have indicated that MIRI is associated with various modes of cell death, including apoptosis, necrosis, autophagy, and ferroptosis. Ferroptosis is a critical factor in these processes. […] The cardiotoxic effects of iron, coupled with its correlation to reperfused MI in individuals with iron overload in the peri-infarct region, underscore the importance of investigating ferroptosis in MIRI. […] Ferroptosis have a vital function in the pathogenesis of MIRI, consequently, ferroptosis inhibition is a possible MIRI therapeutic target. […] Many challenges underlying the mechanism and treatment of MIRI are yet to be investigated. […] In conclusion, ferroptosis showed the potential to an efficient therapeutic target for MIRI. However, further investigation is required to fully uncover its molecular mechanism and potential role in this condition.

• #1 An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives

  https://www.mdpi.com/2073-4409/11/7/1165

  It takes 30–60 min to reestablish physiological calcium levels, and the transient accumulation of this ion in the cytoplasm is sufficient to activate calcium-dependent lipases and proteases and trigger cell hyper-contraction and mitochondrial permeability transition pore (mPTP) opening. […] Overall, these data suggest that both excessive activation and suppression of Nox proteins, compared to physiological levels, may contribute to I/R injury, particularly if they alter adaptive signaling mechanisms. […] Autophagy is one of the primary mechanisms ensuring cardiac homeostasis in response to stress, thus limiting cardiac damage and preserving heart function. […] The role of autophagy has been extensively studied in pre-clinical models of chronic and acute myocardial ischemia. […] Autophagy activation during myocardial ischemia is an adaptive response that limits cardiac injury.

• #1 Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review)

  https://www.spandidos-publications.com/10.3892/etm.2022.11357

  Myocardial infarction is one of the primary causes of mortality in patients with coronary heart disease worldwide. […] The pathophysiological mechanisms leading to MIRI are associated with oxidative stress, intracellular calcium overload, energy metabolism disorder, apoptosis, endoplasmic reticulum stress, autophagy, pyroptosis, necroptosis and ferroptosis. […] In the past, apoptosis and autophagy have attracted more attention but necroptosis and ferroptosis also serve key roles. […] The present study reviews the mechanisms underlying MIRI. […] Evidence has indicated that during myocardial ischemia/reperfusion (MIR), both ischemia and reperfusion cause injury to the ischemic myocardium. […] Therefore, myocardial reperfusion may further aggravate death of ischemic cardiomyocytes in patients with myocardial infarction (MI); this is known as MIR injury (MIRI).

• #1 An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives

  https://www.mdpi.com/2073-4409/11/7/1165

  Restoration of coronary blood flow is essential to save the life of patients with acute MI and reduce myocardial loss. However, myocardial reperfusion also contributes to the extension of MI through excessive production of ROS, intracellular calcium overload and mitochondrial damage, namely the reperfusion injury. […] The concept of biphasic ischemia/reperfusion (I/R) injury is now well established. […] Reperfusion induces a rapid normalization of the extracellular pH that determines the formation of a strong H+ gradient across the plasma membrane. […] The main result is a further massive flow of Na+ inside the cell to enable the expulsion of excess H+ ions through the Na+/H+ exchanger. […] The increase of intracellular Na+ forces the sodium-calcium exchanger (NCX) to operate unconventionally, secreting Na+ outside the cell to balance its accumulation and importing Ca2+.

• #1

  https://www.jci.org/articles/view/62874

  The four recognized forms of myocardial reperfusion injury are discussed in detail below, the first two reversible and the second two irreversible. […] The sudden reperfusion of acutely ischemic myocardium in STEMI patients undergoing PPCI may be accompanied by ventricular arrhythmias, which usually self-terminate or are easily treated (6). […] This form of reperfusion injury results from the detrimental effects of oxidative stress and intracellular calcium overload on the myocardial contractile apparatus (7). […] Importantly, 30%40% of PPCI patients in whom coronary blood flow in the infarct-related coronary artery appears normal on coronary angiography have evidence of MVO as detected by myocardial contrast echocardiography (14, 15), myocardial perfusion nuclear scanning (16), or contrast-enhanced cardiac MRI (17, 18).

• #1

  https://journal.hsforum.com/index.php/HSF/article/view/4725

  Acute myocardial infarction can be treated aggressively with intravenous thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting; however, recanalization can cause myocardial ischemia-reperfusion injury (MIRI). […] Inflammation can regulate cardiomyocyte apoptosis, autophagy, pyroptosis, and necrosis, and is the main initiating factor leading to MIRI in cardiomyocytes. […] This article reviews the mechanism of inflammatory response in the ischemia-reperfusion period after acute myocardial infarction and the clinical value and application prospect of inhibiting inflammatory response in the treatment of acute myocardial infarction.

• #1 Protective approaches against myocardial ischemia reperfusion injury (Review)

  https://www.spandidos-publications.com/10.3892/etm.2016.3877

  Cyclic repetition of this process leads to Ca2+ oscillations that lead to uncontrolled myofibrillar hypercontraction and also promote opening of the mitochondrial permeability transition pore (mPTP). […] The increased Ca2+ oscillations also enhance the activity of xanthine oxidases, promoting the production of ROS, which further exacerbate membrane damage by directly promoting opening of the mPTP, and thus contribute to cell death during reperfusion. […] Neutrophils entering the ischemic zone further aggravate the cellular damage by releasing inflammatory mediators, causing microvascular obstruction and local and eventually systemic inflammation.

• #1 Aging reimagined: Study finds immune resilience counters key drivers of disease, mortality    – UT Health San Antonio

  https://news.uthscsa.edu/aging-reimagined-study-finds-immune-resilience-counters-key-drivers-of-disease-mortality/

  „Our work shows that immune resilience is associated with TCF7, a central master regulator that maintains T-cell health,” said Muthu Manoharan, MS, co-first author and senior research scientist at UT Health San Antonio. […] The study proposes that TCF7-linked immune resilience may counterbalance what the authors term as a “pathogenic triad”—inflammaging (chronic inflammation with aging), immune aging and cell senescence. Immune resilience can diminish over time due to environmental threats (e.g., infections, trauma) or internal stressors (e.g., myocardial ischemia). […] „When salutogenesis declines and pathogenesis emerges, this may create a state of inflammation and immune aging that promotes disease,” Ahuja explained. „Individuals with TCF7-linked immune resilience appear better equipped to resist inflammatory stressors and maintain a low-inflammatory immune profile promoting survival and better health.”

• #1 The Protective Effect and Mechanism of Apigenin in Myocardial Ischemia/Reperfusion Injury by Regulating AMPK/Nrf2/HO-1 Pathway by Jianjun Xu, Xinliang Liu, Xiaoqiang Zhang, Kai Qi, Xiaqin Zha :: SSRN

  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4233883

  Apigenin (Api) has strong antioxidant and anti-inflammatory effects. However, the effect and mechanism of Api on acute myocardial ischaemia/reperfusion (I/R) injury are not fully understood. […] In this study, we assessed whether ferroptosis was involved in acute myocardial I/R injury by using a H9c2 cardiomyocyte-like cells (H9c2 cells) acute anoxia/reoxygenation (A/R) injury model and an acute myocardial I/R injury model in vivo and in vitro, and determined the protective effect and mechanism of Api in acute myocardial I/R injury. […] Api increased the expression of AMPK2, GSK3, Nrf2, and HO-1, decreased the expression of mTOR, and activated the AMPK/Nrf2/HO-1 pathway. […] In conclusion, this study showed that Api inhibited oxidative stress, stabilized mitochondrial function, and improved ferroptosis-mediated acute myocardial I/R injury by activating the AMPK/Nrf2/HO-1 pathway.

• #1

  https://www.jci.org/articles/view/62874

  Reperfusion-induced death of cardiomyocytes that were viable at the end of the index ischemic event is defined as lethal myocardial reperfusion injury (2). The major contributory factors are discussed below and include oxidative stress, calcium overload, mitochondrial permeability transition pore (MPTP) opening, and hypercontracture (3). […] The existence of lethal myocardial reperfusion injury has been inferred in both experimental MI models and in patients with STEMI by the observation that therapeutic interventions applied solely at the onset of myocardial reperfusion reduced MI size by 40%50% (3). […] However, no effective therapy currently exists for reducing lethal myocardial reperfusion injury in patients who have undergone PPCI. […] Many of the above proponents of myocardial reperfusion injury appear to converge on the MPTP. The MPTP is a nonselective channel of the inner mitochondrial membrane, the opening of which results in mitochondrial membrane depolarization and uncoupling of oxidative phosphorylation, leading to ATP depletion and cell death (34, 35).

• #1

  https://www.jci.org/articles/view/62874

  In the setting of acute myocardial IRI, the MPTP has been shown to remain closed during ischemia and only open at reperfusion in response to mitochondrial Ca2+ and phosphate overload, oxidative stress and relative ATP depletion, and rapid pH correction (36). […] The therapeutic intervention should confer conclusive cardioprotection in all experimental animal models tested before being investigated in the clinical setting. […] Acute myocardial IRI is the major cause of the detrimental effects of CHD on the myocardium. This form of myocardial injury is characterized in STEMI patients who present with acute myocardial ischemia, in whom treatment priority is timely and effective myocardial reperfusion using either thrombolytic therapy or PPCI. […] However, this is an active area of ongoing research, with the recent discovery of several mechanical and pharmacologic adjuncts to PPCI for preventing myocardial reperfusion injury.

• #1 An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives

  https://www.mdpi.com/2073-4409/11/7/1165

  However, excessive autophagy can trigger harmful mechanisms in the heart in some circumstances, increasing damage. […] Mitochondrial dynamics should be preserved within physiological levels for appropriate cardioprotection. Ischemic injury shifts the process towards fission, which can be reduced or counteracted by stimulating fusion. […] The above-described evidence suggests that alteration of different molecular mechanisms contributes to worsened cardiac function in response to ischemic injury.

• #1 Silent Myocardial Ischemia: From Pathophysiology to Diagnosis and Treatment

  https://www.mdpi.com/2227-9059/12/2/259

  Silent myocardial ischemia (SMI), characterized by a lack of overt symptoms despite an inadequate blood supply to the myocardium, remains a challenging entity in cardiovascular medicine. The pathogenesis involves intricate interactions of vascular, neurohormonal, and metabolic factors, contributing to perfusion deficits without the characteristic chest pain. […] Mechanistically, SMI involves the occurrence of myocardial ischemia without angina or its equivalents. Spinal cardiac fibers transmit anginal pain through afferent pathways to the thalamus and, subsequently, to the cerebral cortex. Biochemical substances and receptors, including substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors, play crucial roles in the neurotransmission of cardiac pain. […] The ischemic burden, reflecting the combined presence of overt and silent ischemia, correlates with the magnitude, duration, and severity of ischemic episodes. Two critical parameters in SMI genesis are the magnitude of the ischemic stimulus and the pain threshold. The pain threshold may be elevated, leading to a lack of pain sensation, as seen in conditions such as cardiovascular autonomic neuropathy, particularly in diabetic patients. […] In summary, the etiology of silent ischemia in the context of diabetes appears to involve anatomical disruptions in cardiac sensory nerve fibers.

• #1 Myocardial ischemia | PPT

  https://www.slideshare.net/slideshow/myocardial-ischemia/83053173

  Angina pectoris is the major symptom of myocardial ischemia. Angina pectoris most commonly presents as severe pain in the chest. […] Silent ischemia is a particularly dangerous form of myocardial ischemia as there is a lack of clinical symptoms, i.e., ischemia without angina. […] Treatment of myocardial ischemia and the resulting angina can involve two strategies: 1. Increase coronary blood flow by dilating coronary arteries. 2. Reduce cardiac workload by reducing heart rate and/or force of contraction. […] Myocardial infarction or heart attack is an irreversible injury to and eventual death of myocardial tissue that results from ischemia and hypoxia. […] Most heart attacks are the direct result of occlusion of a coronary blood vessel by a lipid deposit. […] A myocardial infarction may be: a) transmural, meaning it involves the full thickness of the ventricular wall, or b) subendocardial, in which the inner one third to one half of the ventricular wall is involved. […] Myocardial infarction is defined as myocardial necrosis due to ischemia that is detected by elevated cardiac biomarkers and clinical signs. […] Myocardial infarction occurs when blood flow to the heart is blocked, depriving heart muscle cells of oxygen and nutrients and causing cell death.

• #1 The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-024-04220-3

  Myocardial ischemia-reperfusion injury (MI/RI) is an unavoidable risk event for acute myocardial infarction, with ferroptosis showing close involvement. […] The ferroptosis-related SLC7A11/GSH/GPX4 pathway was repressed in MI/RI rat myocardial tissues, inducing myocardial injury. […] H/R affected GSH synthesis and inhibited GPX4 enzyme activity by down-regulating SLC7A11, thus promoting ferroptosis in cardiomyocytes, which was averted by Lip-1. […] H/R suppressed the ferroptosis-related SLC7A11/GSH/GPX4 pathway by inducing mitophagy, leading to cardiomyocyte injury. […] Increased ROS under H/R conditions triggered cardiomyocyte injury by inducing mitophagy to suppress the ferroptosis-related SLC7A11/GSH/GPX4 signaling pathway activation. […] MI/RI refers to the damage that occurs in the heart tissues as a result of the worsening of ischemia in the myocardium following the blockage of a coronary artery.

• #1 HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism | Scientific Reports

  https://www.nature.com/articles/srep33636

  Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. […] The development of myocardial I/R injury involves multiple mechanisms. Among of them, endothelial cell (EC) damage has been shown to be a critical mediator. […] Therefore, maintaining ECs integrity serves as a promising therapeutic target for the treatment of myocardial I/R injury. […] This action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. […] The data suggest that HSPA12B maintained endothelial integrity which in turn contributed to the cardioprotection from myocardial I/R injury. […] Activation of PI3K/Akt/mTOR signaling has been well demonstrated in the protection against myocardial I/R injury. […] Most importantly, administration with PI3K inhibitor Wortmannin abolished the HSPA12B-induced attenuation of cardiac dysfunction provoked by myocardial I/R, suggesting that PI3K/Akt/mTOR signaling plays important roles in mediating the cardioprotection of HSPA12B against I/R injury.

• #1 Protective approaches against myocardial ischemia reperfusion injury (Review)

  https://www.spandidos-publications.com/10.3892/etm.2016.3877

  However, it is important to understand the mechanisms of myocardial ischemia-reperfusion injury in order to develop therapies targeting both ischemic and reperfusion damage, to reduce the infarct size, considering that smaller infarct size can lead to better cardiac function, over long-term. […] Myocardial ischemia-reperfusion injury is a complex process, which involves several interrelated factors, including a decrease in cellular adenosine triphosphate (ATP) levels, accumulation of hydrogen ions, calcium overload, and production of reactive oxygen species (ROS). […] The increased availability of ATP upon reperfusion in the presence of increased Ca2+ activates sarcoplasmic reticulum (SR) uptake of Ca2+, exceeding the threshold of ryanodine channels, which release Ca2+ into the cytosol.

• #1 Mechanisms of Myocardial Ischemia in Cancer Patients: A State-of-the-Art Review of Obstructive Versus Non-Obstructive Causes

  https://www.imrpress.com/journal/RCM/23/7/10.31083/j.rcm2307227/htm

  In patients with cancer, myocardial infarction (MI) has distinct features and mechanisms compared to the non-oncology population. […] Triggers of myocardial ischemia specific to the oncology population have been increasingly identified. […] Coronary plaque disruption, coronary vasospasm, coronary microvascular dysfunction, spontaneous coronary artery dissection, and coronary oxygen supply-demand mismatch are all causes of MI that have been shown to have specific triggers related to either the treatments or complications of cancer. […] MI can occur in the presence or absence of atherosclerotic coronary artery disease (CAD). […] MI with nonobstructive CAD (MINOCA) is a heterogeneous syndrome that has distinct pathophysiology and different epidemiology from MI with significant CAD (MI-CAD).

• #1 Myocardial ischemia – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/myocardial-ischemia/diagnosis-treatment/drc-20375422

  The goal of myocardial ischemia treatment is to improve blood flow to the heart muscle. Depending on the severity of your condition, your doctor may recommend medications, surgery or both. […] Sometimes, more-aggressive treatment is needed to improve blood flow. Procedures that may help include: […] A long, thin tube (catheter) is inserted into the narrowed part of your artery. A wire with a tiny balloon is threaded into the narrowed area and inflated to widen the artery. A small wire mesh coil (stent) is usually inserted to keep the artery open. […] A surgeon uses a vessel from another part of your body to create a graft that allows blood to flow around the blocked or narrowed coronary artery. This type of open-heart surgery is usually used only for people who have several narrowed coronary arteries. […] This noninvasive outpatient treatment might be recommended if other treatments haven’t worked. Cuffs that have been wrapped around your legs are gently inflated with air then deflated. The resulting pressure on your blood vessels can improve blood flow to the heart.

• #1 The pathophysiology of myocardial ischaemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1768241/

  The assessment of the relation between the degree of epicardial coronary narrowing and the measured coronary flow reserve is complex and generalisations are difficult. […] The believed pathophysiological basis is microvascular instability that dysregulates coronary blood flow. […] The mechanisms of myocardial ischaemia may differ between patients and within the same patient. An understanding of these different mechanisms is of considerable help in understanding patients symptomatology and their management.

• #1 Clinical significance of chronic myocardial ischemia in coronary artery disease patients – Rezende – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/27749/html

  Myocardial ischemia is considered the cornerstone of the treatment of patients with coronary artery disease (CAD). […] Myocardial ischemia is a multifactorial pathophysiological condition that involves a complex and specific interaction between coronary vessels and the myocardium. Ultimately, it represents an imbalance between myocardial oxygen supply and demand that can occur in different situations. […] The most frequent cause of coronary blood flow limitation is obstruction due to atherosclerosis. […] The presence of collaterals may also play a role in coronary circulation. […] Once ischemia is triggered, anaerobic metabolism of myocytes begins, followed by tissue acidosis from generation of lactic acid and reduction of adenosine triphosphate (ATP) availability. […] After an ischemic insult, and depending on its intensity, duration, and compensatory mechanisms, the myocardium can exhibit distinct responses.

• #2 Ischemic heart disease – McMaster Pathophysiology Review

  https://www.pathophys.org/acs/

  Myocardial ischemia is a consequence of reduced blood flow in coronary arteries, due to a combination of fixed vessel narrowing and abnormal vascular tone as a result of atherosclerosis and endothelial dysfunction. This leads to an imbalance between myocardial oxygen supply and demand. […] In atherosclerotic arteries, however, endothelial dysfunction contributes to myocardial ischemia in the following ways: Inappropriate vasoconstriction of coronary arteries. […] Resulting impairment in blood flow causes a marked imbalance between myocardial oxygen supply and demand. […] The consequences of ischemia reflect the inadequate myocardial oxygenation and local accumulation of metabolic waste products. Ultimately, the severity and duration of imbalance between oxygen supply and demand will determine the fate of the myocardium.

• #2 Clinical significance of chronic myocardial ischemia in coronary artery disease patients – Rezende – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/27749/html

  Myocardial ischemia is considered the cornerstone of the treatment of patients with coronary artery disease (CAD). […] Myocardial ischemia is a multifactorial pathophysiological condition that involves a complex and specific interaction between coronary vessels and the myocardium. Ultimately, it represents an imbalance between myocardial oxygen supply and demand that can occur in different situations. […] The most frequent cause of coronary blood flow limitation is obstruction due to atherosclerosis. […] The presence of collaterals may also play a role in coronary circulation. […] Once ischemia is triggered, anaerobic metabolism of myocytes begins, followed by tissue acidosis from generation of lactic acid and reduction of adenosine triphosphate (ATP) availability. […] After an ischemic insult, and depending on its intensity, duration, and compensatory mechanisms, the myocardium can exhibit distinct responses.

• #2 Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation, and Clinical Applications

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10399947/

  Myocardial ischemia is a major mechanism in the pathogenesis of cardiac dysfunction in a variety of clinical settings. […] In response to impaired coronary blood flow, myocardial ischemic injury is manifested as progressive alteration in function, metabolism, and structure of the affected myocardium. […] Reperfusion halts the progression of myocardial ischemic injury, salvages myocardium by restoration of blood flow, and simultaneously produces sublethal to lethal reperfusion injury in marginally viable myocardium. […] Myocardial ischemic injury is manifested by progressive alterations in high energy phosphate metabolism and electrolyte homeostasis. […] With the onset of myocardial ischemia, oxygen is rapidly depleted, causing mitochondrial respiration to cease, thereby reducing the availability of the high energy phosphate, adenosine triphosphate (ATP).

• #2 Myocardial Ischemia: Causes, Symptoms and Treatment

  https://my.clevelandclinic.org/health/diseases/17848-myocardial-ischemia

  Myocardial ischemia is a lack of blood flow getting to your heart muscle. That means your heart muscle isnt getting enough blood to do what it needs to do. Often, the cause is a collection of fat and cholesterol (plaque) that doesnt let enough blood go through your coronary arteries. Medicines and surgeries can treat myocardial ischemia. […] Myocardial ischemia (or cardiac ischemia) means your heart muscle is not getting enough blood (which contains oxygen and nutrients) to work as it should. If this lack of blood from your coronary arteries is severe or goes on for more than a few minutes, it can damage your heart muscle. Then it becomes a myocardial infarction (heart attack). […] Causes of myocardial ischemia include: […] Coronary artery disease. This is a buildup of plaque and cholesterol inside your coronary arteries, which supply blood to your heart muscle. The buildup narrows your artery so much that the oxygen-rich blood your heart needs cant get through, and your heart muscle becomes starved for oxygen. This causes ischemia and angina. Atherosclerotic plaque causes 70% of fatal heart attacks.

• #2 Myocardial Infarction: Risk Factors, Pathophysiology, Classification, Assessment and Management | Auctores

  https://www.auctoresonline.org/article/myocardial-infarction-risk-factors-pathophysiology-classification-assessment-and-management

  Myocardial infarction (MI) is sudden ischemia of the heart muscle tissue due to lack or obstruction of coronary blood flow, which leads to its damage (Frangogiannis, 2015). […] The central mechanism of the pathophysiology is the same regardless of the etiological factors that may only modify the outcome. For example, hypertension is a main risk factor involved in strokes while smoking increases the incidence of MI (Bentzon et al, 2014). […] Myocardial infarction (MI) results from a severe and prolonged imbalance between the myocardial O2 supply and its requirements. In most cases, this occurs as a result of occlusive coronary atherosclerosis superimposed with luminal thrombus (Christia and Frangogiannis, 2013). […] The pathophysiology process can be summarized in the following steps:

• #2 Myocardial Infarction: Risk Factors, Pathophysiology, Classification, Assessment and Management | Auctores

  https://auctoresonline.org/article/myocardial-infarction-risk-factors-pathophysiology-classification-assessment-and-management

  Coronary endothelial dysfunction precedes the lesion formation and increases with progression of CAD. It results from endothelial injury that occurs in response to oxidized LDL, increased levels of blood glucose, hypertension and increased free radicals derived from oxygen. […] Atherosclerosis is the main cause of plaque formation by causing internal inflammation, fibrosis, necrosis and calcification. […] The direct mechanism is through accumulation of LDLs in the arterial endothelium with an intrinsic adaptive thickening (Bentzon et al, 2014). […] Plaque rupture occurs through the thin fibrous cap. Rupture of vulnerable plaque could be preceded by severe exertion. […] Plaque rupture leads to exposure of blood with the necrotic core that is rich with erythrocytes and highly thrombogenic material leading to clot formation.

• #2 Myocardial Response To Ischemia – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/myocardial-response-to-ischemia

  Cocaine and vasospastic angina can cause coronary artery vasoconstriction, further decreasing the coronary oxygen supply. Diminished coronary oxygen supply can also arise from coronary embolism, dissection, arteritis, myocardial fibrosis, or in systemic hypoxia due to conditions like hypotension, shock, anemia, and carbon monoxide poisoning. […] In ischemic conditions, myocardial cells switch to anaerobic glycolysis within seconds, leading to ATP depletion and myofibril relaxation. […] However, after 30 minutes, the damage becomes irreversible and is indicated by signs like mitochondrial vacuolization, and myocyte cell membrane breakdown which leads to the release of troponin creatine kinase, indicating irreversible cell damage. […] Reperfusion injury can occur during the restoration of blood flow, leading to further cellular damage through the buildup of intracellular calcium during ischemia, which causes hypercontracture and cytoskeletal damage upon reperfusion.

• #2 Cardiac Syndrome X and Myocardial Ischemia: Pathogenesis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4471-4838-8_7

  Cardiac syndrome X (CSX) is characterized by: (1) angina chest pain triggered by effort; (2) ST-segment depression on exercise stress electrocardiogram or other findings compatible with myocardial ischemia; (3) normal coronary arteries at angiography, in absence of any specific cardiac or systemic disease. Myocardial ischemia related to abnormalities in coronary microcirculation is in most cases responsible for the angina symptoms (microvascular angina, MVA). […] The mechanisms responsible for coronary microvascular dysfunction (CMVD) include both reduced coronary microvascular dilation and enhanced coronary microvascular constriction. Moreover, the impaired microvascular dilator function may involve both endothelium-independent and endothelium-dependent mechanisms. […] The causes responsible for CMVD in CSX are also heterogeneous. Traditional cardiovascular risk factors, including hypertension, dyslipidaemia, blood glucose disorders and smoking might play some role. Some conditions frequently found associated with CSX, however, include abnormal adrenergic nerve function, insulin resistance, inflammation and (in women) estrogen deficiency.

• #2

  https://www.jci.org/articles/view/62874

  The deprivation of oxygen and nutrient supply results in a series of abrupt biochemical and metabolic changes within the myocardium (Figure 1). The absence of oxygen halts oxidative phosphorylation, leading to mitochondrial membrane depolarization, ATP depletion, and inhibition of myocardial contractile function. […] During acute myocardial ischemia, the absence of oxygen switches cell metabolism to anaerobic respiration, resulting in the production of lactate and a drop in intracellular pH. This induces the Na+-H+ exchanger to extrude H+ and results in intracellular Na+ overload, which activates the 2Na+-Ca2+ exchanger to function in reverse to extrude Na+ and leads to intracellular Ca2+ overload. […] After the onset of acute myocardial ischemia in patients with STEMI, timely myocardial reperfusion using PPCI is essential to salvage viable myocardium, limit MI size, preserve LV systolic function, and prevent the onset of heart failure. However, the reperfusion of acutely ischemic myocardium can independently induce cardiomyocyte death (13), although this concept has been difficult to accept over the years.

• #2 Myocardial ischemia | PPT

  https://www.slideshare.net/slideshow/myocardial-ischemia/83053173

  Angina pectoris is the major symptom of myocardial ischemia. Angina pectoris most commonly presents as severe pain in the chest. […] Silent ischemia is a particularly dangerous form of myocardial ischemia as there is a lack of clinical symptoms, i.e., ischemia without angina. […] Treatment of myocardial ischemia and the resulting angina can involve two strategies: 1. Increase coronary blood flow by dilating coronary arteries. 2. Reduce cardiac workload by reducing heart rate and/or force of contraction. […] Myocardial infarction or heart attack is an irreversible injury to and eventual death of myocardial tissue that results from ischemia and hypoxia. […] Most heart attacks are the direct result of occlusion of a coronary blood vessel by a lipid deposit. […] A myocardial infarction may be: a) transmural, meaning it involves the full thickness of the ventricular wall, or b) subendocardial, in which the inner one third to one half of the ventricular wall is involved. […] Myocardial infarction is defined as myocardial necrosis due to ischemia that is detected by elevated cardiac biomarkers and clinical signs. […] Myocardial infarction occurs when blood flow to the heart is blocked, depriving heart muscle cells of oxygen and nutrients and causing cell death.

• #2 Different types of cell death and their interactions in myocardial ischemia–reperfusion injury | Cell Death Discovery

  https://www.nature.com/articles/s41420-025-02372-5

  The loss of cardiomyocytes is a certainly outcome of reperfusion injury, which can occur through apoptosis, necroptosis, autophagy, and other pathways, contributing to irreversible damage and cardiac dysfunction. […] During I/R, different types of cell death occur in a specific sequence, accompanied by distinct dynamic changes. […] However, emerging evidence now indicates a significant crosstalk and intricate interplay among these cell death mechanisms, blurring their traditional boundaries. […] Recognizing these processes and their interplay is essential for the formulation of effective therapeutic approaches aimed at alleviating I/R injury. […] During the later reperfusion phase, necroptosis occurs. […] The process involves the production of massive amounts of inflammatory factors, such as TNF-, which activate RIPK1.

• #2

  https://www.jci.org/articles/view/62874

  Reperfusion-induced death of cardiomyocytes that were viable at the end of the index ischemic event is defined as lethal myocardial reperfusion injury (2). The major contributory factors are discussed below and include oxidative stress, calcium overload, mitochondrial permeability transition pore (MPTP) opening, and hypercontracture (3). […] The existence of lethal myocardial reperfusion injury has been inferred in both experimental MI models and in patients with STEMI by the observation that therapeutic interventions applied solely at the onset of myocardial reperfusion reduced MI size by 40%50% (3). […] However, no effective therapy currently exists for reducing lethal myocardial reperfusion injury in patients who have undergone PPCI. […] Many of the above proponents of myocardial reperfusion injury appear to converge on the MPTP. The MPTP is a nonselective channel of the inner mitochondrial membrane, the opening of which results in mitochondrial membrane depolarization and uncoupling of oxidative phosphorylation, leading to ATP depletion and cell death (34, 35).

• #2 Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review)

  https://www.spandidos-publications.com/10.3892/etm.2022.11357

  A recent study indicated that myocardial ferroptosis (as well as apoptosis pyroptosis) is increased during MIRI in diabetes and is attenuated by effective treatment with antioxidant N-acetylcysteine. […] Studies have shown that ferroptosis is involved in regulation of tumor, liver cancer, Alzheimer’s disease, cerebral ischemic and acute kidney injury and other types of disease. […] It is hypothesized that during ischemia and early reperfusion, cellular acidosis, internal environmental instability and other factors promote release of ferrivalent or ferrous ions from enzymes containing iron and sulfur clusters and activate the iron-mediated Fenton reaction, resulting in increased generation of ROS, which leads to oxidative stress injury and ferroptosis of cardiomyocytes. […] Expression levels of necroptosis-associated proteins, including RIPK1, RIPK3 and MLKL, have been shown to be increased in an in vivo MIRI model.

• #2 Myocardial Ischemia/Reperfusion Injury: Mechanism and Targeted Treatment for Ferroptosis The Anatolian Journal of Cardiology

  https://anatoljcardiol.com/article/AJC-00850

  Studies have indicated that MIRI is associated with various modes of cell death, including apoptosis, necrosis, autophagy, and ferroptosis. Ferroptosis is a critical factor in these processes. […] The cardiotoxic effects of iron, coupled with its correlation to reperfused MI in individuals with iron overload in the peri-infarct region, underscore the importance of investigating ferroptosis in MIRI. […] Ferroptosis have a vital function in the pathogenesis of MIRI, consequently, ferroptosis inhibition is a possible MIRI therapeutic target. […] Many challenges underlying the mechanism and treatment of MIRI are yet to be investigated. […] In conclusion, ferroptosis showed the potential to an efficient therapeutic target for MIRI. However, further investigation is required to fully uncover its molecular mechanism and potential role in this condition.

• #2 Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review)

  https://www.spandidos-publications.com/10.3892/etm.2022.11357

  Numerous studies have researched mechanisms underlying MIRI; the pathophysiological mechanisms of MIRI are associated with oxidative stress, intracellular calcium overload, energy metabolism disorder, apoptosis, endoplasmic reticulum stress (ERS), autophagy, pyroptosis, ferroptosis and necroptosis. […] Oxidative stress induced by reperfusion after ischemia is considered to be the primary mechanism of IRI. […] The opening of mPTP may contribute to loss of ATP, mitochondrial swelling and CytC release, leading to apoptosis. […] Previous studies have indicated that apoptotic cell death is one of the primary forms of cardiomyocyte death during MIRI. […] IRI may be associated with ERS. […] During MIRI, ERS is increased and inhibition of ERS has been shown to attenuate MIRI. […] Autophagy, the primary function of which is to remove and recover misfolded or damaged proteins and organelles, is not only associated with cell survival but also with cell death.

• #2

  https://journal.hsforum.com/index.php/HSF/article/view/4725

  Acute myocardial infarction can be treated aggressively with intravenous thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting; however, recanalization can cause myocardial ischemia-reperfusion injury (MIRI). […] Inflammation can regulate cardiomyocyte apoptosis, autophagy, pyroptosis, and necrosis, and is the main initiating factor leading to MIRI in cardiomyocytes. […] This article reviews the mechanism of inflammatory response in the ischemia-reperfusion period after acute myocardial infarction and the clinical value and application prospect of inhibiting inflammatory response in the treatment of acute myocardial infarction.

• #2 The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-024-04220-3

  It has been established that genetic modifications in the ferroptosis pathway effectively impede ferroptosis and reduce myocardial damage. […] Suppressing SLC7A11 expression leads to reductions in GSH/GPX4 activity, while SLC7A11 and its downstream GPX4 or GSH are considered key modulatory genes in ferroptosis, and their downregulation indicates the occurrence of ferroptosis-related damage, such as myocardial injury. […] In this study, we first created an MI/RI rat model and confirmed the protective role of the SLC7A11/GSH/GPX4 pathway in I/RI. […] Our findings unearthed that SLC7A11 could potentially be developed into a new therapeutic target in MI/RI. […] It is interesting to note that upregulation of SLC7A11 ameliorates H/R-induced cardiomyocyte ferroptosis via the GSH/GPX4 signaling pathway.

• #2 Protective approaches against myocardial ischemia reperfusion injury (Review)

  https://www.spandidos-publications.com/10.3892/etm.2016.3877

  However, it is important to understand the mechanisms of myocardial ischemia-reperfusion injury in order to develop therapies targeting both ischemic and reperfusion damage, to reduce the infarct size, considering that smaller infarct size can lead to better cardiac function, over long-term. […] Myocardial ischemia-reperfusion injury is a complex process, which involves several interrelated factors, including a decrease in cellular adenosine triphosphate (ATP) levels, accumulation of hydrogen ions, calcium overload, and production of reactive oxygen species (ROS). […] The increased availability of ATP upon reperfusion in the presence of increased Ca2+ activates sarcoplasmic reticulum (SR) uptake of Ca2+, exceeding the threshold of ryanodine channels, which release Ca2+ into the cytosol.

• #2 Protective approaches against myocardial ischemia reperfusion injury (Review)

  https://www.spandidos-publications.com/10.3892/etm.2016.3877

  Cyclic repetition of this process leads to Ca2+ oscillations that lead to uncontrolled myofibrillar hypercontraction and also promote opening of the mitochondrial permeability transition pore (mPTP). […] The increased Ca2+ oscillations also enhance the activity of xanthine oxidases, promoting the production of ROS, which further exacerbate membrane damage by directly promoting opening of the mPTP, and thus contribute to cell death during reperfusion. […] Neutrophils entering the ischemic zone further aggravate the cellular damage by releasing inflammatory mediators, causing microvascular obstruction and local and eventually systemic inflammation.

• #2 Mechanisms of Myocardial Ischemia in Cancer Patients: A State-of-the-Art Review of Obstructive Versus Non-Obstructive Causes

  https://www.imrpress.com/journal/RCM/23/7/10.31083/j.rcm2307227/htm

  Recognition and differentiation of MI-CAD and MINOCA is essential in the oncology population, due to unique etiology and impact on diagnosis, management, and overall outcomes. […] The purpose of this review is to analyze the literature for studies related to known triggers of myocardial ischemia in cancer patients, with a focus on MINOCA. […] We propose that certain cancer treatments can induce MINOCA-like states, and further research is warranted to investigate mechanisms that may be unique to certain cancer states and types of treatment. […] The epidemiology of these specific causes of MI is different in cardio-oncology patients compared to the general cardiovascular population, given the unique risk profile of cancer patients and various cardiotoxic anti-cancer therapies. […] Supply-demand mismatch in stable CAD is common in cancer patients due to a high risk of anemia, sepsis, tachycardia, and hypovolemia, in this population, although this represents a different mechanism and will be discussed separately.

• #2 The pathophysiology of myocardial ischaemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1768241/

  The assessment of the relation between the degree of epicardial coronary narrowing and the measured coronary flow reserve is complex and generalisations are difficult. […] The believed pathophysiological basis is microvascular instability that dysregulates coronary blood flow. […] The mechanisms of myocardial ischaemia may differ between patients and within the same patient. An understanding of these different mechanisms is of considerable help in understanding patients symptomatology and their management.

• #3 Clinical significance of chronic myocardial ischemia in coronary artery disease patients – Rezende – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/27749/html

  Myocardial ischemia is considered the cornerstone of the treatment of patients with coronary artery disease (CAD). […] Myocardial ischemia is a multifactorial pathophysiological condition that involves a complex and specific interaction between coronary vessels and the myocardium. Ultimately, it represents an imbalance between myocardial oxygen supply and demand that can occur in different situations. […] The most frequent cause of coronary blood flow limitation is obstruction due to atherosclerosis. […] The presence of collaterals may also play a role in coronary circulation. […] Once ischemia is triggered, anaerobic metabolism of myocytes begins, followed by tissue acidosis from generation of lactic acid and reduction of adenosine triphosphate (ATP) availability. […] After an ischemic insult, and depending on its intensity, duration, and compensatory mechanisms, the myocardium can exhibit distinct responses.

• #3 The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-024-04220-3

  Myocardial ischemia-reperfusion injury (MI/RI) is an unavoidable risk event for acute myocardial infarction, with ferroptosis showing close involvement. […] The ferroptosis-related SLC7A11/GSH/GPX4 pathway was repressed in MI/RI rat myocardial tissues, inducing myocardial injury. […] H/R affected GSH synthesis and inhibited GPX4 enzyme activity by down-regulating SLC7A11, thus promoting ferroptosis in cardiomyocytes, which was averted by Lip-1. […] H/R suppressed the ferroptosis-related SLC7A11/GSH/GPX4 pathway by inducing mitophagy, leading to cardiomyocyte injury. […] Increased ROS under H/R conditions triggered cardiomyocyte injury by inducing mitophagy to suppress the ferroptosis-related SLC7A11/GSH/GPX4 signaling pathway activation. […] MI/RI refers to the damage that occurs in the heart tissues as a result of the worsening of ischemia in the myocardium following the blockage of a coronary artery.

• #3 The Protective Effect and Mechanism of Apigenin in Myocardial Ischemia/Reperfusion Injury by Regulating AMPK/Nrf2/HO-1 Pathway by Jianjun Xu, Xinliang Liu, Xiaoqiang Zhang, Kai Qi, Xiaqin Zha :: SSRN

  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4233883

  Apigenin (Api) has strong antioxidant and anti-inflammatory effects. However, the effect and mechanism of Api on acute myocardial ischaemia/reperfusion (I/R) injury are not fully understood. […] In this study, we assessed whether ferroptosis was involved in acute myocardial I/R injury by using a H9c2 cardiomyocyte-like cells (H9c2 cells) acute anoxia/reoxygenation (A/R) injury model and an acute myocardial I/R injury model in vivo and in vitro, and determined the protective effect and mechanism of Api in acute myocardial I/R injury. […] Api increased the expression of AMPK2, GSK3, Nrf2, and HO-1, decreased the expression of mTOR, and activated the AMPK/Nrf2/HO-1 pathway. […] In conclusion, this study showed that Api inhibited oxidative stress, stabilized mitochondrial function, and improved ferroptosis-mediated acute myocardial I/R injury by activating the AMPK/Nrf2/HO-1 pathway.

• #4 HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism | Scientific Reports

  https://www.nature.com/articles/srep33636

  Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. […] The development of myocardial I/R injury involves multiple mechanisms. Among of them, endothelial cell (EC) damage has been shown to be a critical mediator. […] Therefore, maintaining ECs integrity serves as a promising therapeutic target for the treatment of myocardial I/R injury. […] This action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. […] The data suggest that HSPA12B maintained endothelial integrity which in turn contributed to the cardioprotection from myocardial I/R injury. […] Activation of PI3K/Akt/mTOR signaling has been well demonstrated in the protection against myocardial I/R injury. […] Most importantly, administration with PI3K inhibitor Wortmannin abolished the HSPA12B-induced attenuation of cardiac dysfunction provoked by myocardial I/R, suggesting that PI3K/Akt/mTOR signaling plays important roles in mediating the cardioprotection of HSPA12B against I/R injury.

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