scholarly journals THE IMPACT OF ISCHEMIA-REPERFUSION ON LANGENDORFF RABBIT HEART WITH EXPERIMENTAL ATHEROSCLEROSIS

2021 ◽  
Vol 39 (Supplement 1) ◽  
pp. e228
Author(s):  
Cristian Romeo Revnic ◽  
Cosmin Sonea ◽  
Flory Revnic
Keyword(s):  
Ischemia Reperfusion ◽  
Rabbit Heart ◽  
Experimental Atherosclerosis ◽  
The Impact

The Impact of Royal Jelly against Hepatic Ischemia/Reperfusion-Induced Hepatocyte Damage in Rats: The Role of Cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α Signaling Pathways

2020 ◽  
Vol 14 (1) ◽  
pp. 88-100
Author(s):  
Fares E.M. Ali ◽  
Heba M. Saad Eldien ◽  
Nashwa A.M. Mostafa ◽  
Abdulrahman H. Almaeen ◽  
Mohamed R.A. Marzouk ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Royal Jelly ◽  
Ischemia Reperfusion ◽  
Histopathological Changes ◽  
Down Regulation ◽  
Hepatic Ischemia ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion ◽  
The Impact

Objective: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/reperfusion (IR) injury. Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment has lasted for 28 days. Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α signaling pathways.

scholarly journals Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Yang ◽  
Li’e Zang ◽  
Jingwen Cui ◽  
Linlin Wei
Keyword(s):  
Stem Cells ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neural Stem Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cerebral Ischemia Reperfusion ◽  
The Impact

Abstract Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

2006 ◽  
Vol 290 (3) ◽  
pp. C719-C727 ◽  
Author(s):  
Frank C. Chen ◽  
Ozgur Ogut
Keyword(s):  
Reperfusion Injury ◽  
Posttranslational Modifications ◽  
Actin Polymerization ◽  
Time Course ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Concentration ◽  
Cross Sectional ◽  
The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

Abstract 223: The Role Of Angiogenesis In The Myocardial Ischemia/reperfusion Injury In Pregnancy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jingyuan li ◽  
Zoltan Pierre Arany ◽  
Mansoureh Eghbali
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Angiogenic Factor ◽  
Daily Injection ◽  
Rate Pressure Product ◽  
Ctrl Group ◽  
The Impact ◽  
In Pregnancy

Angiogenesis plays an important role in the pathogenesis of cardiovascular disease. Pro-angiogenic and anti-angiogenic treatments have provided new insights into the impact of angiogenesis-based approaches on coronary artery disease. We have recently reported that the hearts of late pregnant (LP) mice are more prone to ischemia/reperfusion (I/R) injury compared to non pregnant(NP) mice. Provided the significant change of angiogenesis status in pregnancy, here we explored whether stimulating the angiogenesis with VEGF is able to protect the heart against I/R injury in late pregnancy, and whether anti-antigenic treatment with soluble endoglin(sENG), an anti-angiogenic factor, aggravates cardiac I/R injury in NP. Pregnant mice at day 12 either received daily injection of VEGF (100 ug/kg daily subcutaneous injection) or PBS(LP CTRL) for 7 days, and at day 19 the LP mice hearts were subjected to 20 min ischemia followed by 40 min reperfusion in Langendorff. NP mice either received a single adenovirus sENG(2х10 8particles via tail vein injection) or vehicle(NP CTRL), and 10 days later NP mice were subjected to 20 min ischemia followed by 40 min reperfusion in Langendorff. The heart function was recorded throughout the experiments, and the infarct size was measured by TTC staining at the end of experiments. Exogenous VEGF treatment significantly improved the cardiac function of LP mice after ischemia. The rate pressure product (RPP) at the end of reperfusion was improved from 1617±287 mmHg*beats/min (n=6) in LP CTRL to 11287±1783 mmHg*beats/min (n=3) in the VEGF group(p<0.01). The infarct size was also significantly reduced by VEGF treatment to 25.0±4.3% (n=3) from 57.4±5.2%(n=6) in CTRL (p<0.01). While sENG aggravated the cardiac I/R injury in NP, as the RPP at the end of reperfusion in the sENG group (4523±1281 mmHg*beats/min, n=4) was significantly lower compared with NP CTRL group(12818±1213 mmHg*beats/min, n=6)(p<0.01). Furthermore, the infarct size in the sENG group was markedly higher compared with NP CTRL group (34.0±3.3% (n=4) vs. 16.3±1.4%(n=6) in NP CTRL, p<0.05). In conclusion, anti-angiogenic treatment aggravates the cardiac I/R injury in NP, while angiogenic therapy protects the heart against I/R injury in LP.

Abstract 328: Hemodynamic Comparison of Zucker Diabetic Fatty Rats to Their Lean Littermates After Asphyxial Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz Baudenbacher ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
Susan Eagle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Arrest ◽  
Ejection Fraction ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Arterial Blood ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
The Impact

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.

Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice

2021 ◽  
Author(s):  
Yuika Osada ◽  
Shunsaku Nakagawa ◽  
Kanako Ishibe ◽  
Shota Takao ◽  
Aimi Shimazaki ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Kidney Injury ◽  
Short Chain Fatty Acids ◽  
Glucose Levels ◽  
The Impact

Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that the bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. The mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, the renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion (IR). Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to IR injury.

Abstract P311: Blocking Succinate Release Enhances Mitochondrial Reactive Oxygen Species Generation And Worsens Ischemia-reperfusion Injury

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Alexander S Milliken ◽  
Sergiy M Nadtochiy ◽  
Paul S Brookes
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen Species Generation ◽  
Ros Generation ◽  
Ros Production ◽  
Succinate Oxidation ◽  
Fluorescence Measurements ◽  
Mitochondrial Ros ◽  
The Impact ◽  
Infarction Heart

Succinate is a metabolite that plays a central role in ischemia-reperfusion (IR) injury,which is relevant to myocardial infarction (heart attack) and stroke. Succinateaccumulates during ischemia and is rapidly consumed at reperfusion driving reactiveoxygen species (ROS) generation at complex-I (Cx-I) and III of the mitochondrial electrontransport chain. This ROS production triggers cell-death, leading to tissue necrosis.Although succinate oxidation has been extensively studied and exploited as a noveltherapeutic target, only 1/3 of the succinate accumulated in ischemia is oxidized atreperfusion, with the remaining 2/3 being released from the cell via monocarboxylatetransporter 1 (MCT1). Extracellular succinate is thought to be pro-inflammatory, and ithas been proposed that preventing succinate release may be therapeutically beneficial.To determine the impact of preventing succinate release on IR injury, we comparedfunctional recovery (i.e. rate x pressure product, RPP) and infarction (i.e. tissue necrosis)of Langendorff perfused mouse hearts treated with an MCT1 inhibitor, AR-C155858,versus vehicle control. This revealed that succinate retention worsens IR injury (i.e.increased infarction and decreased functional recovery) likely due to increased ROS. Totest this hypothesis, we utilized a Langendorff apparatus positioned within aspectrofluorimeter, which permits real-time fluorescence measurements in beatingmouse hearts. Using the mitochondria targeted superoxide probe, MitoSOX red tomeasure ROS production at reperfusion + AR-C155858, demonstrated that succinateretention leads to enhanced mitochondrial ROS generation at the onset of reperfusion.Overall, these results suggest that inhibiting succinate release in the context of IR injurymay not be a viable therapeutic approach, regardless of any downstream anti-inflammatory effects.

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