scholarly journals Evaluating Novel Targets of Ischemia Reperfusion Injury in Pig Models

2019 ◽  
Vol 20 (19) ◽  
pp. 4749 ◽  
Author(s):  
Andrea Baehr ◽  
Nikolai Klymiuk ◽  
Christian Kupatt
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Health Care Systems ◽  
Ischemia Reperfusion ◽  
Developed Countries ◽  
Predictive Capacity ◽  
Coronary Heart Diseases ◽  
Care Systems ◽  
Clinical Experiments

Coronary heart diseases are of high relevance for health care systems in developed countries regarding patient numbers and costs. Disappointingly, the enormous effort put into the development of innovative therapies and the high numbers of clinical studies conducted are counteracted by the low numbers of therapies that become clinically effective. Evidently, pre-clinical research in its present form does not appear informative of the performance of treatments in the clinic and, even more relevant, it appears that there is hardly any consent about how to improve the predictive capacity of pre-clinical experiments. According to the steadily increasing relevance that pig models have gained in biomedical research in the recent past, we anticipate that research in pigs can be highly predictive for ischemia-reperfusion injury (IRI) therapies as well. Thus, we here describe the significance of pig models in IRI, give an overview about recent developments in evaluating such models by clinically relevant methods and present the latest insight into therapies applied to pigs under IRI.

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

2011 ◽  
Vol 301 (5) ◽  
pp. H1723-H1741 ◽  
Author(s):  
Shoji Sanada ◽  
Issei Komuro ◽  
Masafumi Kitakaze
Keyword(s):  
Reperfusion Injury ◽  
Clinical Evidence ◽  
Clinical Medicine ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Developed Countries ◽  
Adverse Outcomes ◽  
Ischemic Heart ◽  
Pathophysiological Mechanism

Heart diseases due to myocardial ischemia, such as myocardial infarction or ischemic heart failure, are major causes of death in developed countries, and their number is unfortunately still growing. Preliminary exploration into the pathophysiology of ischemia-reperfusion injury, together with the accumulation of clinical evidence, led to the discovery of ischemic preconditioning, which has been the main hypothesis for over three decades for how ischemia-reperfusion injury can be attenuated. The subcellular pathophysiological mechanism of ischemia-reperfusion injury and preconditioning-induced cardioprotection is not well understood, but extensive research into components, including autacoids, ion channels, receptors, subcellular signaling cascades, and mitochondrial modulators, as well as strategies for modulating these components, has made evolutional progress. Owing to the accumulation of both basic and clinical evidence, the idea of ischemic postconditioning with a cardioprotective potential has been discovered and established, making it possible to apply this knowledge in the clinical setting after ischemia-reperfusion insult. Another a great outcome has been the launch of translational studies that apply basic findings for manipulating ischemia-reperfusion injury into practical clinical treatments against ischemic heart diseases. In this review, we discuss the current findings regarding the fundamental pathophysiological mechanisms of ischemia-reperfusion injury, the associated protective mechanisms of ischemic pre- and postconditioning, and the potential seeds for molecular, pharmacological, or mechanical treatments against ischemia-reperfusion injury, as well as subsequent adverse outcomes by modulation of subcellular signaling mechanisms (especially mitochondrial function). We also review emerging translational clinical trials and the subsistent clinical comorbidities that need to be overcome to make these trials applicable in clinical medicine.

Prevention of Cerebral Oxidative Injury by Post-ischemic Intravenous Administration of Shengmai San

2006 ◽  
Vol 34 (04) ◽  
pp. 591-600 ◽  
Author(s):  
Haruyo Ichikawa ◽  
Lei Wang ◽  
Tetsuya Konishi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Oxidative Injury ◽  
Protein Carbonyl ◽  
Thiobarbituric Acid Reactive Substance ◽  
Cerebral Ischemia Reperfusion ◽  
Shengmai San

Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus schisandrae and has been used for treating coronary heart diseases (Bensky and Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative injury in rats when it administered into the duodenum before cerebral ischemia-reperfusion. In the present study, we examined whether post-ischemic administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats as well. Results showed that SMS injected immediately after ischemia also prevented the ischemia-reperfusion injury, when the effect was evaluated by the formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS), and the loss of glutathione peroxidase (GPX). The preventative potential of SMS was decreased rapidly dependent on the time lag until SMS was injected after ischemia. However, it was noted that intravenously administered SMS protected the oxidative injury approximately 30% even after 60 min of reperfusion in terms of protein carbonyl formation. It is thus suggested that SMS injection might be useful for preventing the progression of injury in cerebral infarction after stroke.

scholarly journals Molecular Mechanisms of Cardioprotective Actions of Tanshinones

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Hyou-Ju Jin ◽  
Chun-Guang Li
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Salvia Miltiorrhiza ◽  
Ischemia Reperfusion ◽  
Therapeutic Agents ◽  
Cardiac Ischemia ◽  
Mitochondrial Apoptosis ◽  
Lipophilic Compounds ◽  
Coronary Heart Diseases

Tanshinones are lipophilic compounds derived fromSalvia miltiorrhiza(Danshen) that has been widely used to treat coronary heart diseases in China. The cardioprotective actions of tanshinones have been extensively studied in various models of myocardial infarction, cardiac ischemia reperfusion injury, cardiac hypertrophy, atherosclerosis, hypoxia, and cardiomyopathy. This review outlines the recent development in understanding the molecular mechanisms and signaling pathways involved in the cardioprotective actions of tanshinones, in particular on mitochondrial apoptosis, calcium, nitric oxide, ROS, TNF-α, PKC, PI3K/Akt, IKK/NF-κB, and TGF-β1/Smad mechanisms, which highlights the potential of these compounds as therapeutic agents for treating cardiovascular diseases.

scholarly journals High cholesterol diet effects on ischemia–reperfusion injury of the heart

2012 ◽  
Vol 90 (9) ◽  
pp. 1185-1196 ◽  
Author(s):  
Verónica D’Annunzio ◽  
Martín Donato ◽  
Bruno Buchholz ◽  
Virginia Pérez ◽  
Verónica Miksztowicz ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Developed Countries ◽  
Lipid Lowering ◽  
Stunned Myocardium ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Lipid Lowering Effect

Ischemic heart disease is the leading cause of morbi-mortality in developed countries. Both ischemia–reperfusion injury and mechanisms of cardioprotection have been studied for more than 50 years. It is known that the physiopathological mechanism of myocardial ischemia involves several factors that are closely related to its development, of which hypercholesterolemia is one of the main ones. Therefore, the objective of this review was to elucidate the effects of a high-cholesterol diet on normal ventricular function and ischemia–reperfusion injury associated phenomenon such as post-ischemic ventricular dysfunction (stunned myocardium). Although there exist many studies considering several aspects of this physiopathological entity, the majority were carried out on normal animals. Thus, experiments carried out on hypercholesterolemic models are controversial, in particular those evaluating different mechanisms of cardioprotection such as ischemic preconditioning and postconditioning, and cardioprotection granted by drugs such as statins, which apart from exerting a lipid-lowering effect, exert pleiotropic effects providing cardioprotection against ischemia–reperfusion injury. These controversial results concerning the mechanisms of cardioprotection vary according to quality, composition, and time of administration of the high-cholesterol diet, as well as the species used in each experiment. Thus, to compare the results it is necessary to take all of these variables into account, since they can change the obtained results.

scholarly journals Remifentanil preconditioning alleviates myocardial ischemia/reperfusion injury in rats via activating Jagged-1/Notch signaling pathway

2021 ◽  
Author(s):  
Dejun Cao ◽  
Shaoxing Liu ◽  
Mengchang Yang ◽  
Keyu Xie ◽  
Zhuo Zheng ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Notch Signaling Pathway ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion

Ischemic heart diseases have emerged as great threats to human health. Nowadays, restoration of cardiac blood flow supply is widely regarded as a feasible treatment choice for ischemic heart diseases; however, this intervention would contradictorily elicit reperfusion injury. Recently, myocardial ischemia/reperfusion injury (MI/RI) has aroused widespread public concerns. Remifentanil, an ultra-short acting opioid analgesic, is frequently used for surgical anesthesia. Previous studies have demonstrated the cardioprotective effects of remifentanil preconditioning in clinical practice and in vitro experimental models; however, its exact mechanisms remain largely unclear. This study aimed to further evaluate the protective effects of remifentanil preconditioning against MI/RI and elucidate the potential molecular mechanisms. Rat models of MI/RI were successfully established via ligation of left anterior descending coronary artery for 30 minutes and restoration of blood flow for 2 hours. Herein, animal experiments displayed that remifentanil preconditioning could alleviate myocardial damage in rat models of MI/RI. Consistently, cell model experiments implied that remifentanil preconditioning attenuated hypoxia/reoxygenation exposure-induced injury in rat cardiomyocytes. Moreover, our findings verified the involvement of Notch signaling pathway in the protective effects of remifentanil preconditioning. In addition, mechanistic studies revealed that remifentanil preconditioning could up-regulate Jagged-1 expression and that Jagged-1 mediated the cardioprotective effects of remifentanil preconditioning through activating Notch signaling pathway. Taken together, our data indicate that remifentanil preconditioning ameliorates myocardial damage in rat MI/RI models via Jagged-1-mediated Notch signaling pathway activation. Thus, this study may offer some novel clues for understanding the cardioprotective mechanisms of remifentanil preconditioning against MI/RI.

scholarly journals Role of Higenamine in Heart Diseases: A Mini-Review

2022 ◽  
Vol 12 ◽  
Author(s):  
Jianxia Wen ◽  
Mingjie Li ◽  
Wenwen Zhang ◽  
Haoyu Wang ◽  
Yan Bai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Disease ◽  
Reperfusion Injury ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia

Higenamine, a natural product with multiple targets in heart diseases, is originally derived from Aconitum, which has been traditionally used in China for the treatment of heart disease, including heart failure, arrhythmia, bradycardia, cardiac ischemia/reperfusion injury, cardiac fibrosis, etc. This study is aimed to clarify the role of higenamine in heart diseases. Higenamine has effects on improving energy metabolism of cardiomyocytes, anti-cardiac fibroblast activation, anti-oxidative stress and anti-apoptosis. Accumulating evidence from various studies has shown that higenamine exerts a wide range of cardiovascular pharmacological effects in vivo and in vitro, including alleviating heart failure, reducing cardiac ischemia/reperfusion injury, attenuating pathological cardiac fibrosis and dysfunction. In addition, several clinical studies have reported that higenamine could continuously increase the heart rate levels of healthy volunteers as well as patients with heart disease, but there are variable effects on systolic blood pressure and diastolic blood pressure. Moreover, the heart protection and therapeutic effects of higenamine on heart disease are related to regulating LKB1/AMPKα/Sirt1, mediating the β2-AR/PI3K/AKT cascade, induction of heme oxygenase-1, suppressing TGF-β1/Smad signaling, and targeting ASK1/MAPK (ERK, P38)/NF-kB signaling pathway. However, the interventional effects of higenamine on heart disease and its underlying mechanisms based on experimental studies have not yet been systematically reviewed. This paper reviewed the potential pharmacological mechanisms of higenamine on the prevention, treatment, and diagnosis of heart disease and clarified its clinical applications. The literature shows that higenamine may have a potent effect on complex heart diseases, and proves the profound medicinal value of higenamine in heart disease.

scholarly journals Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lei Pang ◽  
Yin Cai ◽  
Eva Hoi Ching Tang ◽  
Michael G. Irwin ◽  
Haichun Ma ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
Prostaglandin E ◽  
Ischemic Heart Diseases ◽  
Ep4 Receptor ◽  
Arachidonic Acids

Prostaglandin E2(PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac-specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects.

1843: Role of Cxcr2 in Renal Ischemia/Reperfusion Injury

2004 ◽  
Vol 171 (4S) ◽  
pp. 487-487
Author(s):  
Motoo Araki ◽  
Masayoshi Miura ◽  
Hiromi Kumon ◽  
John Belperio ◽  
Robert Strieter ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury
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