Mitochondria may deteriorate under various pathological conditions, including ischemia reperfusion ir injury. Mitochondrial transplantation in myocardial ischemia and. Oct 06, 2019 this phenomenon has been suggested and obliquely shown in heart preservation, transplantation and reperfusion, and in cardiac cold ischemia reperfusion injury cir. Myocardial ischemia reperfusion injuryfrom basic science to clinical.
Many changes, including free radical production, calcium overload, protease activation, altered membrane lipids and leukocyte activation, contribute to iriinduced myocardium damage. Similar to the cns, a key consequence of gastrointestinal i. Mitochondria may deteriorate under various pathological conditions, including ischemiareperfusion ir injury. Three weeks later, hearts were isolated and perfused isovolumically under constant perfusion pressure conditions. Background myocardial ischemia reperfusion ir injury is a leading cause of death all over the world, so developing practical approaches to promote cardioprotection against ir injury is essential. Acute myocardial ischemiareperfusion ir injury is a significant, unsolved clinical puzzle. Although fatty acids are the predominant fuel of energy metabolism in the normal adult heart, glucose is an important preferential substrate under specific pathological conditions, such as ischemiareperfusion injury iri, as it provides greater efficiency for producing highenergy products per oxygen molecule consumed than fatty acids 1,2,3,4,5,6. Gastrointestinal ischemia reperfusion injury ischemia reperfusion of the gastrointestinal tract is associated with a variety of pathologic conditions and surgical procedures, including strangulated bowel, vascular surgery, and hemorrhagic shock. Cardiac ischemia reperfusion injury iri occurs when the myocardium is revascularized after an episode of limited or absent blood supply. Reperfusion injury occurs when tissue perfusion and oxygenation are restored to an affected area after an ischemic event. In pathological states, such as cardiac ischemia reperfusion ir injury, this ermitochondria microdomains may act to participate in the cellular redox imbalance, er stress, mitochondrial injury, energy deletion and programmed cell death. The beneficial effects of exercise cardiac ischemia reperfusion injury iri occurs when the myocardium is revascularized after an episode of.
Lucchesi, phd, md reperfusion of coronary arteries to limit myocardi al ischemic injury and extent of myocardial necrosis is possible by either the use of fibrinolytic therapy, coronary angiopiasty or coronary artery bypass surgery. There is no doubt that early reperfusion, both pharmacological and mechanical, is the only way to prevent progression to myocardial necrosis and thus to limit the size of. Ischemiareperfusion injury iri occurring with ischemia and restoration of blood flow to postischemic tissue, is associated with arrhythmias, myocardial necrosis and apoptosis resulting in increased mortality and morbidity. Reperfusion therapies, including primary percutaneous coronary intervention and fibrinolytic therapy, promptly restore blood flow to ischemic myocardium and limit infarct size. Mechanisms underlying acute protection from cardiac. Myocardial ischemia reperfusion injury is accompanied by an inflammatory response contributing to reversible and irreversible changes in tissue viability and organ function.
All hearts were perfused for 20 min for equilibration. Clinical manifestations and basic mechanisms of myocardial. The aim of this thesis was to gain knowledge about the complex pathophysiology behind. Pkcs promotes cardiac ischemia reperfusion injury through mitigating bi. Cardiac functional recovery after ischemiareperfusion injury with or without phlorizinperfusion. Rats were ovariectomized, not ovariectomized, or ovariectomized and treated with subcutaneous estrogen pellets 1. Heterogeneous mitochondrial damage has also been shown more directly by fluorescent confocal microscopy 43,45,99. Cardiac ischemia may be asymptomatic or may cause chest pain, known as angina pectoris. Calcium overload, ph recovery, and ros overproduction are major players in determining iri mitochondria play a pivotal. In the clinical realm, these include reperfusion for acute myocardial infarction ami and angioplasty and after cabg surgery and exercise.
Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50%. Request pdf myocardial ischemia and reperfusion injury. Reperfusion injury an overview sciencedirect topics. Reperfusion strategies are required to resuscitate the ischemic myocardium. Myocardial injury in the setting of an acute myocardial infarction is the result of ischemic and reperfusion injury. In the disease context of acute myocardial infarction, reperfusion. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction. Ischemiareperfusion injury iri occurs as an inevitable consequence of the transplant process, beginning with organ procurement and preservation and followed by reperfusion of the donor organ with recipient blood during transplant 1. Myocardium ischemic damage is most of the causing of disability and deaths in civilized worldwide. Jun 15, 2018 in pathological states, such as cardiac ischemia reperfusion ir injury, this ermitochondria microdomains may act to participate in the cellular redox imbalance, er stress, mitochondrial injury, energy deletion and programmed cell death. Mechanisms of cardiac protection from ischemiareperfusion injury. They are also a source of reactive oxygen species ros and proapoptotic factors. Briefly, mptp is formed by a ring of the c subunits of the adenosine triphosphate atp synthase. The role of cytoprotective cytokines in cardiac ischemiareperfusion injury.
Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. Neutrophil activity is also implicated in reperfusion injury. Ischaemiareperfusion injury iri is defined as the paradoxical exacerbation of cellular. Metabolomic characterization of myocardial ischemia. In either case c 60 exposure exacerbated myocardial infarction. Acute myocardial infarction mi is a major cause of death and disability worldwide.
Massive cardiomyocyte death occurs during acute myocardial infarction but emergency coronary recanalization is usually not able to prevent it. Humanin exerts neuroprotection during cardiac ischemia. Interaction of cardiovascular risk factors with myocardial. Cardiac ischemiareperfusion injury is inversely affected by thyroid hormones excess or deficiency in male wistar rats, plos one, 2018, volume, issue 1, doi. C60 exposure augments cardiac ischemiareperfusion injury. Importantly, mice injected with mir173p agomir were protected from adverse remodeling aftercardiac ischemia reperfusion injury. Prostaglandin pg i 2 and thromboxane tx a 2 are major prostanoids in the cardiovascular system. Roles of prostaglandin i2 and thromboxane a2 in cardiac. Evolving therapies for myocardial ischemiareperfusion injury jacc. Mechanisms of cardiac protection from ischemia reperfusion injury. Ischemia reperfusion injury iri occurring with ischemia and restoration of blood flow to postischemic tissue, is associated with arrhythmias, myocardial necrosis and apoptosis resulting in increased mortality and morbidity. The cpk activity released into the perfusate was measured at the point in the protocol indicated by the solid arrows. Obligatory hibernators such as the ground squirrels show resistance to ischemia reperfusion ir injury in liver, heart, and small intestine during the hibernation season when there is a switch from carbohydrate metabolism to lipid metabolism for cellular energy supply. Susceptibility to cardiac ischemiareperfusion injury is mod.
In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many. In the clinical realm, these include reperfusion for acute myocardial infarction ami and angioplasty and after cabg surgery and exercise or stressinduced ischemia. Susceptibility to cardiac ischemiareperfusion injury is. The involvement of apoptosis and necrosis are also. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size.
Ischemia is defined as inadequate blood supply to a part of the body, usually caused by partial or total blockage of an artery. Myocardial ischemia occurs when blood flow to your heart is reduced, preventing the heart muscle from receiving enough oxygen. It occurs when the heart muscle, or myocardium, receives insufficient blood flow this most frequently results from atherosclerosis, which is the longterm accumulation of cholesterolrich plaques in the coronary arter. Naseer ahmed, in pathophysiology of ischemia reperfusion injury and use of fingolimod in cardioprotection, 2019. Fundamentals of reperfusion injury for the clinical. In patients with mi, the treatment of choice for reducing acute myocardial ischemic injury and limiting mi size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention ppci. Human tissueengineered model of myocardial ischemia. Ischemia reperfusion injury and medicolegal issues. Methods and resultsmice c57bl6j, male, 8 to 12 weeks of age were subjected to either myocardial ischemia or myocardial ischemia and reperfusion for up to 28 days. Antiarrhythmogenic effects of quercetin postconditioning. Given that cardiac ischemia is either unpredictable mi or inevitable in the operating room, there is great interest in developing strategies to minimize reperfusion. Early reperfusion reduced mortality in ami so that, in many countries, the hospital mortality has declined to about 5%. The relative roles of ischemia and reperfusion in irreversible injury are discussed.
Myocardial ischemia symptoms and causes mayo clinic. Current mechanistic concepts in ischemia and reperfusion injury. Nos is a major oxidative stress factor in the liver, heart, and aortic endothelial cells 1416. Pdf pathophysiology of myocardial ischemia reperfusion injury. Mechanisms of ischemiareperfusion injury iri european society. The aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia. Oct 12, 2017 cardiac ischemia reperfusion injury iri occurs when the myocardium is revascularized after an episode of limited or absent blood supply. This most frequently results from atherosclerosis, which is the longterm accumulation of cholesterolrich plaques in the coronary arteries. The pathological manifestation of coronary artery disease is a myocardial injury, which is produced upon ischemia reperfusion ir insult. The role of mitochondria in the mechanisms of cardiac.
Pathophysiology, clinical manifestations, and prevention of. In this study, we utilized cardiac tissue engineering methods and cardiomyocytes derived from human induced pluripotent stem cells to establish a human tissueengineered model of iri. The ir groups were subjected to 20 min of global ischemia and 40 min of reperfusion, while the nonir groups were perfused continuously for 80 min without global ischemia. Data from murine models have indicated that liver iri has.
Gastrointestinal ischemiareperfusion injury ischemiareperfusion of the gastrointestinal tract is associated with a variety of pathologic conditions and surgical procedures, including strangulated bowel, vascular surgery, and hemorrhagic shock. Within each delivery route, infarct sizes in the male groups were larger than those in. Stsegment elevation myocardial infarction is of great individual and. The reduced blood flow is usually the result of a partial or complete blockage of your hearts arteries coronary arteries. Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial. Neutrophils use the destructive capabilities of free radicals to attack bacteria, and there is evidence that they also act on reperfused tissue. Myocardial ischemia, reperfusion and free radical injury. The failure to develop new therapeutic options that are able to effectively prevent reperfusion injury fully reflects the complexity of this process. In the last decades, a number of different strategies have been investigated figure 1. Iri occurs in a wide range of organs including the heart, lung, kidney, gut. Effects of slit2 on post ischemia reperfusion ir cardiac function. During ischemia, the metabolic shift towards anaerobiosis promotes calcium overload and longfatty. Pulmonary damage following bilateral hind limb ischemia was significantly.
It occurs when the heart muscle, or myocardium, receives insufficient blood flow. The role of cytoprotective cytokines in cardiac ischemia. The role of mitochondria has been established in many aspects of cell physiologypathophysiology, including cell signaling. Pathophysiology, clinical manifestations, and prevention. Ischemiareperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Our previous study showed that humanin treatment at 84. Myocardial ischemia, reperfusion and free radical injury benedict r.
Current strategies to reduce ischemic damage and reperfusion injury. Cardioprotection of dapagliflozin and vildagliptin in rats. Reperfusion reduces infarct size and enhances the rate of survival. The aim of the study was to discover the metabolomic changes in plasma that occur during human ischemiareperfusion ir injury and to evaluate the. Sodiumglucose cotransporter 2 inhibitor sglt2i effects on cardiac ischemiareperfusion ir injury are unclear. Cardiac ischemiareperfusion injury under insulinresistant. Endothelial and leukocyte responses are involved in tissue injury, orchestrated primarily by the complement cascade. In a quest to ameliorate various points in pathways from mitochondrial damage to myocardial necrosis, exhaustive pharmacologic and genetic tools have targeted various mediators of ischemia and reperfusion injury and procedural techniques without applicable success. We intended to clarify these roles of pgi2 and txa2 using mice lacking the pgi2 receptor, ip 22 mice, or the txa2 receptor, tp 22 mice. Ischemic heart disease is the most common cause of death in most western countries and. Mitochondria are therefore a likely site of reperfusion induced oxidative damage, the severity of which may increase with age. Conditions under which ischemiareperfusion injury is encountered include the different forms of acute vascular occlusions stroke, myocardial infarction, limb. The aim of this thesis was to gain knowledge about the complex pathophysiology behind myocardial reperfusion injury. Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarctionderived damage and to heal injury.
Myocardial ischemia reperfusion injury an overview. Finally, rat hearts were induced ischemia reperfusion injury for the purpose of infarct size analysis and determination of signal transduction. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Histopathological changes in myocardial tissues were determined using inverted microscope. Ischemiareperfusion injury following acute myocardial. Finally, rat hearts were induced ischemiareperfusion injury for the purpose of infarct size analysis and. Reperfusion therapies, including primary percutaneous coronary intervention and fibrinolytic therapy, promptly restore blood flow.
Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. Myocardial ischemia, also called cardiac ischemia, reduces the heart muscles ability to pump. Myocardial ischemia and reperfusion injury, clinical and. Pathophysiology of reperfusion injury mechanisms of vascular. Cardiac ischemiareperfusion injury is inversely affected by. Unlike sglt2i, dipeptidyl peptidase 4 inhibitors dpp4i have shown effective cardioprotection in cardiac ir injury. Mechanisms underlying acute protection from cardiac ischemia. Slit2 protects hearts against ischemiareperfusion injury. Impact of lymphangiogenesis on cardiac remodeling after. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. Although timely restoration of coronary blood flow reperfusion is the most effective therapeutics of myocardial infarction, reperfusion causes further cardiac damage, i. Sodiumglucose cotransporter 2 inhibitor sglt2i effects on cardiac ischemia reperfusion ir injury are unclear. Diagram depicts critical events in cardiac ischemia reperfusion injury suleiman et al 2001. Myocardial ischemia australia pdf ppt case reports.
Roles of calcium regulating micrornas in cardiac ischemia. The resulting cardiac constructs were subjected to conditions that simulated ischemiareperfusion. Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production. Diabetic parameters and cardiac functions were assessed. Protein expressions were measured by western blotting, while enzymelinked immunosorbent assay elisa was used to assay the expression levels of caspase3. Mitochondria are therefore a likely site of reperfusioninduced oxidative damage, the severity of which may increase with age. Myocardial ischemiareperfusion, free radicals, noreflow, necrosis, antioxidants.
This phenomenon has been suggested and obliquely shown in heart preservation, transplantation and reperfusion, and in cardiac cold ischemiareperfusion injury cir. Myocardial ischemiareperfusion injury is accompanied by an inflammatory response contributing to reversible and irreversible changes in tissue viability and organ function. Mitochondrial permeability transition pore mptp independent of the mechanisms accounting for the reperfusion damage, mptp opening is considered to be the key driver of injury. Ermitochondria microdomains in cardiac ischemiareperfusion. Section ii discusses mechanisms involved in cell death in cardiac ischemiareperfusion. To test the hypothesis that bag3 protects the heart from reperfusion injury, in vivo cardiac function was measured in hearts infected with either recombinant adenoassociated virus serotype 9expressing raav9expressing bag3 or gfp and subjected to ir.
C60 exposure augments cardiac ischemiareperfusion injury and. But reperfusion may also, in itself, cause reversible injury, stunning and arrhythmias, as well as irreversible lethal reperfusion injury. Cardiac ischemiareperfusion injury is inversely affected. Ischemiareperfusion injury is associated with serious clinical manifestations, including myocardial.
Pathogenesis of myocardial ischemiareperfusion injury and. Ischemia reperfusion injury iri occurring with ischemia and restoration of blood flow to post ischemic tissue, is associated with arrhythmias, myocardial necrosis and apoptosis resulting in increased mortality and morbidity. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies. Pdf mechanisms of cardiac protection from ischemia. Section ii discusses mechanisms involved in cell death in cardiac ischemia reperfusion. The damage inflicted on the myocardium during acute myocardial infarction is the result. Male and female rats were subjected to regional cardiac ir 20120 min injury in situ, 24 h following intratracheal it or intravenous iv delivery of c 60 or vehicle. Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Similar to the cns, a key consequence of gastrointestinal ir is the. Analysis revealed that both models increased the protein expression of vascular. Pathophysiology, clinical manifestations, and prevention of ether. Role of p38 inhibition in cardiac ischemiareperfusion injury.
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