Abstract T P212: The Impact of the Method of Ischemia/reperfusion Injury on Stroke Outcomes in Type 2 Diabetes

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
Zhi Qu ◽  
Handong Ma ◽  
Roshini Prakash ◽  
Md Nasrul Hoda ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Functional Outcome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Motor Deficit ◽  
Vascular Protection ◽  
Gk Rats ◽  
The Impact

Diabetes worsens functional outcome after ischemic stroke and is associated with greater hemorrhagic transformation (HT) occurrence. We have shown that male diabetic Goto-Kakizaki (GK) rats develop greater HT and neurological deficit despite smaller infarcts after temporary (3/21 hr) middle cerebral artery occlusion (MCAO) induced by the suture model. The impact of the duration of ischemia/reperfusion (I/R) and the method of ischemia on neurovascular injury and functional outcome in diabetic stroke remain unknown. To address this gap, control Wistar and diabetic GK rats were subjected to 90 min/23 hr, 3 hr/21 hr, or 3 hr/7 day MCAO by suture occlusion or embolus placement. In all groups, infarct size, edema, HT occurrence and severity (hemoglobin level), and functional outcome (grip strength and composite deficit score) were measured (Table). Infarct size was smaller in GK rats with suture or embolic MCAO, but expanded with longer reperfusion period. Edema, HT occurrence and severity were all increased in GK rats after 90 min and 3 hr occlusion with the suture model, but not in the embolic MCAO. Motor deficit was greater in diabetic rats. These findings suggest that diabetes accelerates the development of HT and amplifies vascular damage especially in the suture model where blood flow is rapidly reestablished. These results highlight the importance of earlier vascular protection to improve neurological outcome of acute ischemic stroke in diabetes.

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.

scholarly journals Up-regulation of miR-499a-5p decreases cerebral ischemia/reperfusion injury by targeting PDCD4

2021 ◽  
Author(s):  
Weifeng Shan ◽  
Huifeng Ge ◽  
Bingquan Chen ◽  
Linger Huang ◽  
Shaojun Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Tunel Staining ◽  
Cerebral Ischemia Reperfusion

Abstract MiR-499a-5p was significantly down-regulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found the plasma levels of miR-499a-5p were significantly down-regulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.

Abstract 496: Genetic Neutrophil Deficiency Ameliorates Cerebral Ischemia-Reperfusion Injury

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ryan A Frieler ◽  
Yutein Chung ◽  
Jianrui Song ◽  
Thomas M Vigil ◽  
Richard M Mortensen
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Knockout Mice ◽  
Neutralizing Antibodies ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Artery Occlusion ◽  
Cross Reactivity

Background: Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Neutralizing antibodies and inhibition of neutrophil chemotactic molecules can be protective during models of stroke, but many of these techniques have the potential to result in cross-reactivity and non-specificity with other immune cell types. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Methods: Myeloid Mcl1 knockout mice were subjected to transient 90-min middle cerebral artery occlusion and infarct size was assessed by MRI after 24 hours reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry after 24 hours reperfusion. Results: We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1 +/+ : 78.0 mm 3 ; MyMcl1 +/- : 83.4 mm 3 ; MyMcl1 -/- : 55.1 mm 3 ). This was accompanied by a nearly complete absence of neutrophils in the ischemic hemisphere of myeloid Mcl1 knockout mice. Although myeloid Mcl1 knockout mice were protected from cerebral infarction, no significant differences in the expression of inflammatory genes were detected. Inhibition of neutrophil chemotaxis using CXCR2 pepducin treatment partially reduced neutrophil mobilization and recruitment to the brain after stroke, but did not reduce infarct size 24 hours after transient MCA occlusion. Conclusions: These data confirm that neutrophils have an important role in infarct development during stroke pathophysiology and suggest that complete deficiency, but not partial inhibition, is necessary to prevent neutrophil-mediated injury during stroke.

scholarly journals Metoprolol blunts the time-dependent progression of infarct size

2020 ◽  
Vol 115 (5) ◽  
Author(s):  
Manuel Lobo-Gonzalez ◽  
Carlos Galán-Arriola ◽  
Xavier Rossello ◽  
Maribel González‐Del‐Hoyo ◽  
Jean Paul Vilchez ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Primary Angioplasty ◽  
Primary Outcome Measure ◽  
Artery Occlusion ◽  
Area At Risk ◽  
Perfusion Computed Tomography ◽  
Myocardial Ischemia Reperfusion

Abstract Early metoprolol administration protects against myocardial ischemia–reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

scholarly journals Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo

2004 ◽  
Vol 286 (5) ◽  
pp. H1649-H1653 ◽  
Author(s):  
Yiru Guo ◽  
Adam B. Stein ◽  
Wen-Jian Wu ◽  
Wei Tan ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
At Risk ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Effective Means ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Water Soluble ◽  
Arterial Blood

Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 ± 3.5% vs. 36.5 ± 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 ± 4.9% of the region at risk ( n = 13) vs. 47.7 ± 3.8% ( n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.

scholarly journals Simulated urban carbon monoxide air pollution exacerbates rat heart ischemia-reperfusion injury

2010 ◽  
Vol 298 (5) ◽  
pp. H1445-H1453 ◽  
Author(s):  
G. Meyer ◽  
L. André ◽  
S. Tanguy ◽  
J. Boissiere ◽  
C. Farah ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Environmental Factors ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Urban Pollution ◽  
Epidemiological Studies ◽  
Lactate Dehydrogenase Release ◽  
Intracellular Ca ◽  
The Impact

Myocardial damages due to ischemia-reperfusion (I/R) are recognized to be the result of a complex interplay between genetic and environmental factors. Epidemiological studies suggested that, among environmental factors, carbon monoxide (CO) urban pollution can be linked to cardiac diseases and mortality. The aim of this work was to evaluate the impact of exposure to CO pollution on cardiac sensitivity to I/R. Regional myocardial I/R was performed on isolated perfused hearts from rats exposed for 4 wk to air enriched with CO (30–100 ppm). Functional variables, reperfusion ventricular arrhythmias (VA) and cellular damages (infarct size, lactate dehydrogenase release) were assessed. Sarcomere length shortening and Ca2+ handling were evaluated in intact isolated cardiomyocytes during a cellular anoxia-reoxygenation protocol. The major results show that prolonged CO exposure worsens myocardial I/R injuries, resulting in increased severity of postischemic VA, impaired recovery of myocardial function, and increased infarct size (60 ± 5 vs. 33 ± 2% of ischemic zone). The aggravating effects of CO exposure on I/R could be explained by a reduced myocardial enzymatic antioxidant status (superoxide dismutase −45%; glutathione peroxidase −49%) associated with impaired intracellular Ca2+ handling. In conclusion, our results are consistent with the idea that chronic CO pollution dramatically increases the severity of myocardial I/R injuries.

scholarly journals Comparative Effects of Verapamil, Nicardipine, and Nitroglycerin on Myocardial Ischemia/Reperfusion Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Hitoshi Yui ◽  
Uno Imaizumi ◽  
Hisashi Beppu ◽  
Mitsuhiro Ito ◽  
Munetaka Furuya ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Control Group ◽  
Area At Risk ◽  
Group A

The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have (1) infarct size-limiting effects and (2) antiarrhythmic effects inin vivorabbit hearts during ischemia/reperfusion. Rabbits received regional ischemia by 30 min of left anterior descending coronary artery occlusion followed by 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a verapamil group, a nicardipine group, and a nitroglycerin group. A continuous infusion of verapamil, nicardipine, or nitroglycerin was initiated 5 min prior to ischemia. Infarct size/area at risk decreased in verapamil, and nitroglycerin. The incidence of ischemia-induced arrhythmia decreased in nicardipine, verapamil and nitroglycerin. The incidence of reperfusion-induced arrhythmias decreased in verapamil and nitroglycerin. From the present experimental results, verapamil and nitroglycerin rather than nicardipine did afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model.

Cytoprotective effects ofN,N,N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes

2007 ◽  
Vol 293 (4) ◽  
pp. H2462-H2471 ◽  
Author(s):  
Susheel Gundewar ◽  
John W. Calvert ◽  
John W. Elrod ◽  
David J. Lefer
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Biological Effects ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Wild Type ◽  
Obesity And Diabetes

N, N, N-Trimethylsphingosine chloride (TMS), a stable N-methylated synthetic sphingolipid analog, has been shown to modulate protein kinase C (PKC) activity and exert a number of important biological effects, including inhibition of tumor cell growth and metastasis, inhibition of leukocyte migration and respiratory burst, and inhibition of platelet aggregation. We hypothesized that TMS would be cytoprotective in clinically relevant in vivo murine models of myocardial and hepatic ischemia-reperfusion (I/R) injury. Wild-type, obese ( ob/ ob), and diabetic ( db/ db) mice were subjected to 30 min of left coronary artery occlusion followed by 24 h of reperfusion in the myocardial I/R model. In additional studies, mice were subjected to 45 min of hepatic artery occlusion followed by 5 h of reperfusion. TMS was administered intravenously at the onset of ischemia. Myocardial infarct size, cardiac function, and serum liver enzymes were measured to assess the extent of tissue injury. TMS attenuated myocardial infarct size by 66% in the wild type and by 36% in the ob/ ob mice. Furthermore, TMS reduced serum alanine transaminase levels by 43% in wild-type mice. These benefits did not extend to the ob/ ob mice following hepatic I/R or to the db/ db mice following both myocardial and hepatic I/R. A likely mechanism is the failure of TMS to inhibit PKC-δ translocation in the diseased heart. These data suggest that although TMS is cytoprotective following I/R in normal animals, the cytoprotective actions of TMS are largely attenuated in obese and diabetic animals.

Protective Effect of Capparis spinosa Extract Against Focal Cerebral Ischemia-Reperfusion Injury in Rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Rakhshandeh ◽  
Samira Asgharzade ◽  
Mohammad Bagher Khorrami ◽  
Fatemeh Forouzanfar
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Public Health Problem ◽  
Artery Occlusion ◽  
Stroke Group ◽  
Capparis Spinosa

Background: Ischemic stroke is a serious public health problem. Despite extensive research focusing on the area, little is known about novel treatments. Objective: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. Methods: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content and malondialdehyde (MDA) levels, were measured 24 hr. after the termination of MCAO. Results: Pretreatment with C. spinosa, reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared with the stroke group. Conclusion: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through attenuation of suppressing oxidative stress.

Abstract 1616: The Role For Caveolin And Caveolae In Delayed Protection From Ischemia-reperfusion Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yasuo M Tsutsumi ◽  
Yoshihiro Ishikawa ◽  
David M Roth ◽  
Hemal H Patel
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Volatile Anesthetics ◽  
Wild Type ◽  
Cardiac Protection ◽  
Glut 4 ◽  
Discontinuous Sucrose Gradient ◽  
The Impact

Introduction: Caveolae are small, flask-like invaginations of the plasma membrane. Caveolins are structural proteins found in caveolae that have scaffolding properties to allow organization of signaling. We have recently shown that both caveolin-1 and caveolin-3 knockout (Cav-1 KO and Cav-3 KO, respectively) mice are unable to be protected from myocardial ischemia-reperfusion injury by acute treatment with volatile anesthetics. Therefore, we tested the hypothesis that delayed cardiac protection induced by volatile anesthetics is caveolin-dependent. Methods: Biochemical assays were performed in excised hearts. Electron microscopy was used to assess caveolae formation. An in vivo mouse model of ischemia-reperfusion injury with delayed anesthetic preconditioning (delayed APC) was tested in wild-type (WT), Cav-1 KO, and Cav-3 KO mice. Mice were exposed to 30 min isoflurane or oxygen and allowed to recover for 24 h. After 24 h recovery, mice underwent 30 min left anterior descending coronary artery occlusion, followed by 2 h of reperfusion at which time infarct size was determined. Results: To elucidate a role for caveolins in delayed APC, wild-type mice were exposed to delayed APC and hearts were fractionated on a discontinuous sucrose gradient to isolate buoyant caveolar membranes. Delayed APC increased the amount of Cav-3 protein but not Cav-1 protein in buoyant fractions. Glucose transporter-4 (GLUT-4), known to interact with Cav-3 and affect cardiac protection, was also increased in buoyant fractions after APC. Microscopically distinct caveolae were observed in WT and Cav-1 KO mice but not Cav-3 KO mice. We assessed the impact of caveolae formation in induction of delayed APC. Infarct size as a percent of the area at risk was reduced by isoflurane in WT (24.0 ± 2.5% vs. 45.1 ± 2.9%, p < 0.05) and Cav-1 KO mice (27.2 ± 4.4%). Cav-3 KO mice did not show delayed APC (41.5 ± 2.2%). Conclusions: These results demonstrate that isoflurane-induced delayed preconditioning involves translocation of Cav-3 and GLUT-4 to caveolae and the presence of microscopically distinct caveolae (dependent on Cav-3 expression) are a requisite for induction of delayed protection in the myocardium. This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada & Utah).

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