scholarly journals Empagliflozin protects the heart against ischemia/reperfusion-induced sudden cardiac death

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhaoyang Hu ◽  
Feng Ju ◽  
Lei Du ◽  
Geoffrey W. Abbott
Keyword(s):  
Coronary Artery ◽  
Sudden Cardiac Death ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Cardiac Death ◽  
Ischemia Reperfusion ◽  
Sglt2 Inhibitor ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Myocardial Ischemia And Reperfusion

Abstract Background Empagliflozin is a selective sodium–glucose cotransporter 2 (SGLT2) inhibitor used to lower blood sugar in adults with type 2 diabetes. Empagliflozin also exerts cardioprotective effects independent from glucose control, but its benefits on arrhythmogenesis and sudden cardiac death are not known. The purpose of this study was to examine the effect of empagliflozin on myocardial ischemia/reperfusion-provoked cardiac arrhythmia and sudden cardiac death in vivo. Methods Male Sprague Dawley rats were randomly assigned to sham-operated, control or empagliflozin groups. All except for the sham-operated rats were subjected to 5-min left main coronary artery ligation followed by 20-min reperfusion. A standard limb lead II electrocardiogram was continuously measured throughout the experiment. Coronary artery reperfusion-induced ventricular arrhythmogenesis and empagliflozin therapy were evaluated. The hearts were used for protein phosphorylation analysis and immunohistological assessment. Results Empagliflozin did not alter baseline cardiac normal conduction activity. However, empagliflozin eliminated myocardial vulnerability to sudden cardiac death (from 69.2% mortality rate in the control group to 0% in the empagliflozin group) and reduced the susceptibility to reperfusion-induced arrhythmias post I/R injury. Empagliflozin increased phosphorylation of cardiac ERK1/2 after reperfusion injury. Furthermore, inhibition of ERK1/2 using U0126 abolished the anti-arrhythmic action of empagliflozin and ERK1/2 phosphorylation. Conclusions Pretreatment with empagliflozin protects the heart from subsequent severe lethal ventricular arrhythmia induced by myocardial ischemia and reperfusion injury. These protective benefits may occur as a consequence of activation of the ERK1/2-dependent cell-survival signaling pathway in a glucose-independent manner.

scholarly journals The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha Sadek El Derh ◽  
Samar Mohamed Abdel Twab ◽  
Mohamed Elgouhary
Keyword(s):  
Coronary Artery ◽  
Cardiac Index ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Off Pump ◽  
Coronary Artery Revascularization

Abstract Background Off pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease. Methods We divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration. Results This study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO. Conclusions This study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

scholarly journals Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Fadhil G. Al-Amran ◽  
Najah R. Hadi ◽  
Haider S. H. Al-Qassam
Keyword(s):  
Myocardial Ischemia ◽  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

Abstract 442: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis via Mir122 Induction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jingyuan Li ◽  
Negar Motayagheni ◽  
Neusha Barakati ◽  
Mansoureh Eghbali
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Microarray Analysis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Late Pregnancy ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Microrna Microarray

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.

scholarly journals The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gino A. Kurian ◽  
Rashmi Rajagopal ◽  
Srinivasan Vedantham ◽  
Mohanraj Rajesh
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Defenses ◽  
Common Denominator ◽  
Myocardial Ischemia And Reperfusion ◽  
Reductive Stress ◽  
Myocardial Infraction

Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions.

scholarly journals Noninvasive Delayed Limb Ischemic Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by a Mitochondrial KATP Channel-Dependent Mechanism

2011 ◽  
pp. 271-279 ◽  
Author(s):  
Y.-N. WU ◽  
H. YU ◽  
X.-H. ZHU ◽  
H.-J. YUAN ◽  
Y. KANG ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Katp Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Dependent Mechanism

We previously demonstrated in rats that noninvasive delayed limb ischemic preconditioning (LIPC) induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb per day for three days confers the same cardioprotective effect as local ischemic preconditioning of the heart, but the mechanism has not been studied in depth. The aim of this project was to test the hypothesis that delayed LIPC enhances myocardial antioxidative ability during ischemia-reperfusion by a mitochondrial KATP channel (mito KATP)-dependent mechanism. Rats were randomized to five groups: ischemia-reperfusion (IR)-control group, myocardial ischemic preconditioning (MIPC) group, LIPC group, IR-5HD group and LIPC-5HD group. The MIPC group underwent local ischemic preconditioning induced by three cycles of 5-min occlusion and 5-min reperfusion of the left anterior descending coronary arteries. The LIPC and LIPC-5HD groups underwent LIPC induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb using a modified blood pressure aerocyst per day for three days. All rats were subjected to myocardial ischemia-reperfusion injury. The IR-5HD and LIPC-5HD groups received the mito KATP channel blocker 5-hydroxydecanoate Na (5-HD) before and during the myocardial ischemia-reperfusion injury. Compared with the IR-control group, both the LIPC and MIPC groups showed an amelioration of ventricular arrhythmia, reduced myocardial infarct size, increased activities of total superoxide dismutase, manganese-superoxide dismutase (Mn-SOD) and glutathione peroxidase, increased expression of Mn-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration. These beneficial effects of LIPC were prevented by 5-HD. In conclusion, delayed LIPC offers similar cardioprotection as local IPC. These results support the hypothesis that the activation of mito KATP channels enhances myocardial antioxidative ability during ischemia-reperfusion, thereby contributing, at least in part, to the anti-arrhythmic and anti-infarct effects of delayed LIPC.

scholarly journals NARINGIN ATTENUATES OXIDATIVE STRESS AND PROTECT AGAINST MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN DIABETIC RAT

2019 ◽  
pp. 230-234
Author(s):  
NEELAM KUMARI ◽  
AJAY SINGH KUSHWAH
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Coronary Artery Ligation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Objective: The relative risk of coronary heart disease in diabetic patients is more than in non-diabetic population. The present study was undertaken to explore the cardioprotective effect of Naringin on ischemia-reperfusion injury in the diabetic model of rat. Methods: Adult Wistar rats (either sex) divided into six groups. Diabetes was induced by 5 weeks combine exposure to a high-fat diet with a low dose of streptozotocin (30 mg/kg i.p.), administered on the 1st day of starting of the 5th week. Naringin treatment 25 mg/kg and 50 mg/kg was given simultaneously for 5 weeks. On the 36th day, the study animals were subjected to induction myocardial ischemia-reperfusion injury induced by the ligation of the left anterior descending coronary artery ligation in anesthetizing rat. Serum glucose level and cholesterol level measured before performing of ischemic reperfusion. After reperfusion injury, the animals were sacrificed and estimate change in the heart in the course of biochemical alterations, in creatine kinase-muscle/ brain (CK-MB) and lactate dehydrogenase, lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and infarct size in the heart. Results and Conclusion: Naringin treatment significantly reduced the body weight, blood glucose, cholesterol, cardiac injury biomarkers, and LPO level and increased in antioxidant (GSH and SOD) level and also significantly increased in mean arterial pressure heart rate, reduced the myocardial infarction size. The present study concludes that Naringin 50 mg/kg being more prominent action to reduce the cardiotoxicity risk in ischemia-reperfusion injury state and increases myocardial susceptibility through having more prominent antioxidant potential properties.

Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning

2000 ◽  
Vol 279 (1) ◽  
pp. H116-H121 ◽  
Author(s):  
Hui-Lin Pan ◽  
Shao-Rui Chen ◽  
Gloria M. Scicli ◽  
Oscar A. Carretero
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Interstitial Fluid ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Period

Ischemic preconditioning is known to protect the myocardium from ischemia-reperfusion injury. We examined the transmural release of bradykinin during myocardial ischemia and the influence of ischemic preconditioning on bradykinin release during subsequent myocardial ischemia. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery in anesthetized cats. Cardiac microdialysis was performed by implantation and perfusion of dialysis probes in the epicardium and endocardium. In eight animals, bradykinin release was greater in the endocardium than in the epicardium (14.4 ± 2.8 vs. 7.3 ± 1.7 ng/ml, P < 0.05) during 30 min of ischemia. In seven animals subjected to preconditioning, myocardial bradykinin release was potentiated significantly from 2.4 ± 0.6 ng/ml during the control period to 23.1 ± 2.5 ng/ml during 30 min of myocardial ischemia compared with the non-preconditioning group (from 2.7 ± 0.6 to 13.4 ± 1.9 ng/ml, P < 0.05, n = 6). Thus this study provides further evidence that transmural gradients of bradykinin are produced during ischemia. The results also suggest that ischemic preconditioning enhances bradykinin release in the myocardial interstitial fluid during subsequent ischemia, which is likely one of the mechanisms of cardioprotection of ischemic preconditioning.

scholarly journals Study on the Protective Effect of Edaravone on Myocardial Ischemia Reperfusion Injury

2013 ◽  
Vol 2 ◽  
pp. 10
Author(s):  
Hui Hou
Keyword(s):  
Treatment Group ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Myocardial Ischemia ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

<div><p><strong>Objective: </strong>Discussion the role of edaravone as a free radical scavenger in protective effect of thrombolysis in acute myocardial ischemia reperfusion injury. Besides compared with the control group and analyze the possible mechanism which is widely used in clinical setting. <strong>Method: </strong>80 patients hospitalized within year 2012−2013 with acute myocardial infarction (AMI) were treated with intravenous thrombolytic therapy, and were divided into treatment group (n = 41) and control group (n = 39). Edaravone injection 30 mg + 0.9% normal saline solution 100 mL with intravenous drip, BID for 14 days was given to the treatment group before and after thrombolytic treatment. Whereas, control group was treated with intravenous drip of placebo. Both groups were monitored by echocardiography and hemodynamic monitoring, and the myocardium was measured by echocardiography. Coronary artery CT was used to determine the degree of obstruction. <strong>Results: </strong>Compared with the control group, pain and reperfusion arrhythmia in treatment group was reduced. The area of myocardial wall movement disorder was significantly decreased (<em>p</em> &lt; 0.05), the difference was statistically significant. CT result comparing treatment group and control group and show that rate of coronary recanalization increases 1.7 times (<em>p </em>&lt; 0.01), the differences were statistically significant. <strong>Conclusion: </strong>For acute myocardial ischemia injection of edaravone before reperfusion and combine with pharmacological treatment can alleviate myocardial ischemia reperfusion injury, effectively scavenge oxygen free radicals and improve the ability of antioxidant. Both improve the thrombolytic treatment and protective effect for acute myocardial ischemia were significant. Hence, edaravone can is a kind of new milestone in the clinical cardiovascular drugs.</p></div>

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