Progression Of Infarction Research Articles

Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats.

Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After two weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure and echocardiography measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. MI was induced and cardiac parameters were measured 7 weeks later. Fractional shortening (FS) was decreased to 18.4±1.0% in vehicle-treated MI rats compared with corresponding sham (30.6±1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7±0.7%), markedly increased heme oxygenase-1 immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13% and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.

Cannabinoid receptor 2 deletion deteriorates myocardial infarction through the down-regulation of AMPK-mTOR-p70S6K signaling-mediated autophagy.

Cannabinoid receptor 2 (CB2R) has been reported to play an important role in the regulation of pathogenesis and progression of myocardial infarction (MI). Here we tried to investigate its potential mechanisms. The ratio of infarct size in heart issue was detected by TTC staining, and cardiac functions were calculated according to echocardiographic evaluation. Cell viability in cardiomyocytes was investigated by Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Western blot was used to detect autophagy-related proteins including Beclin-1, LC3, p62, adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K) signaling-related proteins including AMPK, mTOR, p70S6K, and their phosphorylation formation. Rapamycin was used for the induction of autophagy. Cleaved caspase-3 and Bax were detected for analyzing apoptosis. TEM was used for the detection of autophagosomes. We found that CB2R deletion (CB2R KO) largely deteriorated the severity of MI and the cardiac function as well as cell viability of cardiomyocytes. Knocking out CB2R decreased the level of autophagy in heart issues from MI mice as well as cardiomyocytes under oxygen-glucose deprivation (OGD). Furthermore, CB2R dysfunction significantly attenuated the cardiac protective effects of rapamycin both in vivo and in vitro. Finally, we found that CB2R-mediated autophagy was induced by AMPK-mTOR-p70S6K signaling pathway. Our current study demonstrated for the first time that CB2R deletion led to a detrimental effect of MI through the dysfunction of AMPK-mTOR-p70S6K signaling pathway, which might provide a novel insight in the treatment of MI.

The Elevated Soluble ST2 Predicts No-Reflow Phenomenon in ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Aim: The primary percutaneous procedure resulted in a significant improvement in the prognosis of myocardial infarction. However, no-reflow phenomenon restrains this benefit of the process. There are studies suggesting that soluble suppression of tumorigenicity (sST2) can be valuable in the diagnosis and progression of heart failure and myocardial infarction. In this study, we aimed to investigate the effect of sST2 on no-reflow phenomenon in ST-elevated myocardial infarction (STEMI).Method: This study included 379 patients (258 men; mean age, 60 ± 11 years) who underwent primary percutaneous treatment for STEMI. sST2 levels were measured from blood samples taken at admission. Patients were divided into two groups according to Thrombolysis in Myocardial Infarction(TIMI) flow grade: group 1 consists of TIMI 0,1,2, accepted as no-reflow, and group 2 consists of TIMI 3, accepted as reflow.Results: No-reflow phenomenon occurred in 60 patients (15.8%). The sST2 level was higher in the no-reflow group (14.2 ± 4.6 vs. 11.3 ± 5.0, p = 0.003). Moreover, regression analysis indicated that diabetes mellitus, lower systolic blood pressure, multivessel vascular disease, high plaque burden, and grade 0 initial TIMI flow rate were other independent predictors of the no-reflow phenomenon in our study. Besides, when the patients were divided into high and low sST2 groups according to the cut-off value from the Receiver operating characteristics analysis, being in the high sST2 group was associated with 2.7 times increased odds for no-reflow than being in the low sST2 group.Conclusion: sST2 is one of the independent predictors of the no-reflow phenomenon in STEMI patients undergoing primary percutaneous coronary intervention.

ACE inhibitor suppresses cardiac remodeling after myocardial infarction by regulating dendritic cells and AT2 receptor-mediated mechanism in mice

Dendritic cells (DCs) play a complex role in the progression of myocardial infarction (MI). The impact of angiotensin-converting enzyme (ACE) inhibitor therapy, partly via affecting DCs maturation and recruitment, was tested on a MI mouse model. Furthermore, the cardioprotective effects of ACEI were enhanced through attenuating migration of DCs from the spleen into peripheral circulation, thereby inhibiting DCs maturation and tissue inflammation. ACEI repress DCs immune inflammatory response through down-regulating DCs maturation surface markers and regulating inflammatory cytokines, which led to a higher survival rate, improved function and remodeling through decreased inflammatory response after MI. However, inhibition of AT2R activation, resulted in a reduction of ACEI effects on DCs. The potent anti-inflammatory effect of ACEI can partially be attributed to its impact on DCs through activation of AT2R, which may provide a new target mechanism for ACEI therapy after MI.

Association of lncRNA polymorphisms with triglyceride and total cholesterol levels among myocardial infarction patients in Chinese population

AimThe long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in the development and progression of myocardial infarction (MI). In this study, we hypothesized that genetic variant of cyclin-dependent kinase inhibitor 2B antisense RNA (ANRIL) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) may affect the prognosis of MI patients. MethodsThe study included 401 Han Chinese MI patients and 409 controls. Four lncRNA tag single nucleotide polymorphisms (SNPs)—ANRIL rs9632884 and rs1537373, MALAT1 rs619586 and rs3200401—were selected. SNP genotyping was performed by an improved multiplex ligation detection reaction assay. Resultsrs9632884 and rs3200401 SNPs were significantly associated with lipid levels in both controls and MI patients (P < 0.003–0.046). Several SNPs interacted with sex and age to modify total cholesterol, low-density lipoprotein cholesterol, and creatinine levels to modify the risk of MI. No association between the lncRNAs SNPs and susceptibility to MI was found (P > 0.05 for all). ConclusionsTaken together, this study provides additional evidence that genetic variation of the ANRIL rs9632884 and MALAT1 rs3200401 can mediate lipid levels in MI patients.

Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

The effective therapeutic approach of cerebral infarction is limited because of its underlying complexity. Recently, multiple long noncoding RNAs (lncRNAs) have been identified in the pathogenesis of cerebral infarction. Here, the current study aims to explore the interaction among lncRNA cyclin-dependent kinase inhibitor-2B-antisense RNA 1 (CDKN2B-AS1), transcription factor B-cell lymphoma/leukemia 11A (BCL11A), and MAPKK kinase kinase 1 (MAP4K1) and further investigate whether they affect cerebral infarction progression. The expression of CDKN2B-AS1, BCL11A, and MAP4K1 was altered in lymphocytes extracted from patients with cerebral infarction. In order to identify their roles in regulatory T (Treg) cells, the proliferation and apoptosis of the CD4+CD25+ Treg cells were examined, and levels of IL-4, IL-10, and TGF-β were determined. Also, the RNA crosstalk among CDKN2B-AS1, BCL11A, and MAP4K1 was validated. Finally, we established a rat model of middle cerebral arterial occlusion to evaluate the neurologic impairment and cerebral infarction volume. The results revealed that lymphocytes in patients with cerebral infarction presented with the up-regulated expression of CDKN2B-AS1. Moreover, BCL11A could specifically bind to CDKN2B-AS1 and MAP4K1 promoter so as to inhibit MAP4K1. Moreover, it was observed that down-regulated CDKN2B-AS1 inhibited CD4+CD25+ Treg-cell proliferation, reduced levels of IL-4, IL-10, and TGF-β and cerebral infarction volume, and elevated MAP4K1 expression. Collectively, our study provides evidence that CDKN2B-AS1 silencing could increase MAP4K1 expression to inhibit the CD4+CD25+ Treg-cell proliferation by reducing enrichment of transcription factor BCL11A, thereby protecting against cerebral infarction progression, highlighting a promising therapeutic strategy for treating cerebral infarction.-Lei, J.-J., Li, H.-Q., Mo, Z.-H., Liu, K.-J., Zhu, L.-J., Li, C.-Y., Chen, W.-L., Zhang, L. Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

IMPACT OF MEAN PLATELET VOLUME ON ST RESOLUTION FOLLOWING THROMBOLYSIS IN ACUTE ST ELEVATION MYOCARDIAL INFARCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Changing in size, density, and reactivity of platelets play an important role in occurrence and progression of myocardial infarction. Increased mean platelet volume (MPV) increases the incidence of fibrinolytic failure in ST segment elevation myocardial infarction (STEMI). Electrocardiographic

Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats.

Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio- and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of post-myocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (Ped) and reduced fractional shortening (FS) and the peak rate of pressure development [+(dP/dt)max] in untreated HanSD compared to sham (non-MI) group [Ped: 30.5 ± 3.3 vs. 9.7 ± 1.3 mmHg; FS: 11.1 ± 1.0 vs. 40.8 ± 0.5%; +(dP/dt)max: 3890 ± 291 vs. 5947 ± 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [Ped: 19.4 ± 2.2 mmHg; FS: 14.9 ± 1.0%; +(dP/dt)max: 5278 ± 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.

Abstract WP83: Stroke Severity and Collaterals are Associated With Infarct Progression During Inter-Facility Transfer for Endovascular Thrombectomy

Introduction: Endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Transfer from a referring hospital (RH) to a comprehensive stroke center (CSC) renders some patients ineligible for EVT due to infarct expansion. We evaluated the association of clinical and imaging factors, and the effect of time on infarct expansion using CT ASPECTS decay, subsequent impact on thrombectomy decision and consequent clinical outcomes. Methods: We retrospectively analyzed data on patients with AIS from LVO transferred for potential EVT from a RH to our comprehensive stroke center (hub) between September 2015 and December 2017. Patients were stratified into two groups, CT decay vs. CT non-decay, where CT ASPECTS decay was defined as deterioration of score from ≥6 at RH to &lt;6 at hub (since AHA guidelines for EVT are ASPECTS &gt; 6). Baseline characteristics, clinical and imaging variables were assessed for association with decay. Good outcomes (90 day mRS 0-2) were compared between the two groups. Multivariable logistic regression was applied to identify the independent predictors for decay and the adjusted odds ratio (aOR) was calculated. Results: Of a total 154 patients, 32 (21%) had ASPECTS decay. Baseline characteristics were similar in both groups except patients with decay had higher NIHSS [Median (IQR), 21(16, 25) vs. 16 (11, 21); P &lt;. 001] and poor collateral scores (mTICI 0-1) [n (%) 17 (68) vs. 22 (29); P 0.003]. Of the 101 patients that did not undergo EVT on arrival to hub, 26 were due to decay in ASPECTS, 20 due to absence of LVO and 19 due to clinical improvement. Transfer time was similar in patients with decay vs. non-decay [Median (IQR), minutes, 164 (124.5, 198.5) vs. 155.5 (117, 191); P 0.64]. Higher initial NIHSS [aOR 1.12 (95% CI: 1.03, 1.23); P 0.009] and poor collateral score [aOR 4.65 (95% CI: 1.65, 13.07); P 0.004] were associated with decay. None of the patients with decay had a good outcome [n (%), 0 (0) vs.41 (41); P &lt;0.0001]. Conclusion: In patients transferred for potential EVT, severity of stroke at initial presentation and poor collateral circulation had significant impact on ASPECTS deterioration. This information can be employed to develop stroke systems of care to triage patients with LVO to a CSC

Abstract TP34: Malignant CT Perfusion Profile is Associated With Increased Sensitivity to Blood Pressure Reductions During Endovascular Stroke Therapy

Background: After large-vessel occlusion (LVO), blood flow to the ischemic penumbra largely depends on collateral perfusion. Blood pressure (BP) reductions during endovascular therapy (EVT) have been associated with increased infarct size and unfavorable functional outcome. We hypothesized that patients with poor collateral circulation assessed using CT perfusion imaging are at increased risk for infarct progression associated with intraprocedural BP reductions. Methods: We prospectively enrolled 90 patients with LVO stroke who underwent perfusion imaging and EVT at two comprehensive stroke centers. Volumes of arterial tissue delay &gt;10 seconds (ATD10) were estimated with RAPID software; a malignant profile was defined as ADT10 &gt;100 ml. BP reduction was defined as the difference between baseline mean arterial pressure (MAP) at the start of EVT and the lowest MAP during the procedure. Sustained relative hypotension was calculated as the area between baseline MAP and continuous measurements of intraprocedural MAP. Results: Sixty-seven patients (mean age 67 ± 15, 38 F, mean NIHSS 16) who were successfully revascularized (TICI 2B/3) were included in analysis. Mean baseline MAP was 119 ± 23 mmHg and median BP reduction was 28 (IQR 20 - 53). These values did not differ significantly among those with malignant (n=19) and non-malignant (n=48) collateral profiles, yet average infarct volume on follow-up was significantly greater among patients with poor collaterals (65 mL vs 32 ml) after adjusting for age and admission NIHSS (p=0.029). A significant interaction was found between the malignant collateral profile and intraprocedural BP reduction (p=0.02, Figure 1A&amp;B). Conclusions: Patients with malignant collateral profiles are more sensitive to BP reductions during EVT, leading them to develop significantly larger infarcts. These results emphasize the importance of intraprocedural blood pressure management for this at-risk group.

Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke

Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression.

Selective Activation of Cannabinoid Receptor 2 Attenuates Myocardial Infarction via Suppressing NLRP3 Inflammasome

The administration of cannabinoid receptor 2 (CB2R) agonist has been reported to produce a cardioprotective effect against the pathogenesis and progression of myocardial infarction (MI). Here in this study, we investigated the specific mechanism related to inflammatory suppression. JWH-133 was used for the activation of CB2R. MI mice models and cardiomyocytes under oxygen-glucose deprivation (OGD) challenge were used for the in vivo and in vitro studies, respectively. Detection of cardiac infarct size and levels of myocardial enzymes as well as echocardiographic examination were applied to assess MI severity and cardiac function. Cell viability and lactate dehydrogenase (LDH) release were detected in vitro. Real-time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the levels of proinflammatory cytokines. Western blot was used for the analysis of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation. We found that the administration of CB2R agonist attenuated the severity of MI through reducing infarct size ratio and levels of myocardial enzymes and improved cardiac function in ejection fraction (EF), fractional shortening (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) in MI mice. JWH-133 also produced a cardioprotective effect in murine primary cardiomyocytes by improving cell viability and LDH release. JWH-133 largely reduced the production and secretion of proinflammatory cytokines, which was significantly attenuated by AM630. HU308 showed the same effects as JWH-133. Taken together, we demonstrated for the first time the cardioprotective effect of CB2R agonist and its NLRP3 inflammasome-related mechanism in MI.

Approaches to therapeutic angiogenesis for ischemic heart disease.

Ischemic heart disease (IHD) is caused by the narrowing of arteries that work to provide blood, nutrients, and oxygen to the myocardial tissue. The worldwide epidemic of IHD urgently requires innovative treatments despite the significant advances in medical, interventional, and surgical therapies for this disease. Angiogenesis is a physiological and pathophysiological process that initiates vascular growth from pre-existing blood vessels in response to a lack of oxygen. This process occurs naturally over time and has encouraged researchers and clinicians to investigate the outcomes of accelerating or enhancing this angiogenic response as an alternative IHD therapy. Therapeutic angiogenesis has been shown to revascularize ischemic heart tissue, reduce the progression of tissue infarction, and evade the need for invasive surgical procedures or tissue/organ transplants. Several approaches, including the use of proteins, genes, stem/progenitor cells, and various combinations, have been employed to promote angiogenesis. While clinical trials for these approaches are ongoing, microvesicles and exosomes have recently been investigated as a cell-free approach to stimulate angiogenesis and may circumvent limitations of using viable cells. This review summarizes the approaches to accomplish therapeutic angiogenesis for IHD by highlighting the advances and challenges that addresses the applicability of a potential pro-angiogenic medicine.

Outcomes in Children with Severe Vasculopathy from Sickle Cell Anemia after Treatment with Chronic Transfusion, Surgical Revascularization and/or Allogenic Hematopoetic Stem Cell Transplantation

Background: Cerebral vasculopathy is a frequent complication of sickle cell anemia (SCA) and is associated with a high risk for stroke. This vasculopathy seen in SCA can be progressive and severe. Sickle cell patients with severe vasculopathy, including Moyamoya syndrome are at increased risk for neurological disabilities and death. While chronic transfusions decrease the risk of stroke in SCA; unfortunately, progression of vasculopathy can occur despite treatment. Limited data exists regarding long term outcomes for this population. We evaluated effectiveness of three treatment approaches at our center, namely chronic transfusions, surgical revascularization plus chronic transfusions and allogenic hematopoietic stem cell transplant (HSCT).Methods: A retrospective chart review was preformed to identify patients with SCA (hemoglobin SS, Sβ0) and severe vasculopathy including Moyamoya syndrome between 1986 to 2017. Severe vasculopathy was defined as having at least one cerebral artery with > 70% stenosis and/or occlusion as seen on MR angiogram (MRA), CT angiogram (CTA) or conventional angiogram (DSA) as determined by a neuroradiologist at our institution. Patients were identified from an institutional stroke database. Patients were included for analysis if they received at least one of the following: chronic transfusions, surgical revascularization (i.e. encephalo-duro-arterio-synagiosis (EDAS) plus chronic transfusions or HSCT. For HSCT, all graft types (bone marrow, peripheral blood stem cells, umbilical cord blood), conditioning regimens and donor types (related, unrelated and haploidentical) were included. Time to event analyses were performed from the time of intervention (transfusion, HSCT, EDAS/chronic transfusions) using overt clinical stroke, new silent infarcts, progression of vasculopathy or new vasculopathy. Survival curves were analyzed using the log-rank (Mantel-Cox) test.Results: Of 35 patients identified, 54% (n =19) underwent chronic transfusions, 23% (n=8) of patients underwent HSCT after being on chronic transfusions, 23% (n=8) underwent EDAS with chronic transfusions and 1 patient underwent each of the above three modalities (Table 1). Median age at time of intervention was similar for all three cohorts (Table 1). Males were overrepresented in all treatment arms (62.5-79% of patients). Average hemoglobin level prior to intervention was also similar: 7.6 g/dL (IQR 7.1-8.3) for the chronic transfusion cohort, 7.3 gm/dL (IQR 6.3-8.2) for the HSCT cohort, and 7.5 gm/dL (IQR 7.2-8) for the EDAS/chronic transfusion cohort. Absolute reticulocyte count was 492.9 K/ul (IQR 358.4-550) for the chronic transfusion group, 389.4 (IQR 174.3-449) for HSCT, and 250.2 (IQR 107.3-393) for EDAS/chronic transfusions (p=0.08). One patient died of overt stroke in the chronic transfusion cohort. The median follow-up times for the transfusion, HSCT and EDAS plus transfusion groups were 4.4, 2.4 and 6 years respectively.Time from date of intervention (transfusion, HSCT, EDAS) to overt clinical or silent stroke was evaluated (Fig 1). Two of the nineteen patients in the chronic transfusion cohort suffered an overt stroke, while one of eight and two of eight had strokes in the post-HSCT and EDAS plus chronic transfusion cohorts respectively. Fourteen of nineteen (74%) in the chronic transfusion cohort had progression of severe vasculopathy after being on transfusions while two of eight (25%) in the HSCT and four of the eight (50%) patients in the EDAS plus chronic transfusion cohorts had progression. The one patient with all three different interventions did not have additional infarction (clinical or silent) or vasculopathy progression during 1.5 years of follow-up.Conclusions: The risk for cerebral infarction and/or vasculopathy progression after initiation of treatment with either chronic transfusion, HSCT or EDAS is still a major concern. Our data suggest HSCT and surgical revascularization with chronic transfusion provide the greatest benefit in reducing stroke risk and HSCT reduces risk for progression of a severe vasculopathy. Additional, large population studies are needed to clarify the risk. [Display omitted] DisclosuresMajumdar:NIMHD: Research Funding. Campbell:Functional Fluitics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Fish, Fish Oils and Cardioprotection: Promise or Fish Tale?

Fish and commercially available fish oil preparations are rich sources of long-chain omega-3 polyunsaturated fatty acids. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most important fatty acids in fish oil. Following dietary intake, these fatty acids get incorporated into the cell membrane phospholipids throughout the body, especially in the heart and brain. They play an important role in early brain development during infancy, and have also been shown to be of benefit in dementia, depression, and other neuropsychiatric disorders. Early epidemiologic studies show an inverse relationship between fish consumption and the risk of coronary heart disease. This led to the identification of the cardioprotective role of these marine-derived fatty acids. Many experimental studies and some clinical trials have documented the benefits of fish oil supplementation in decreasing the incidence and progression of atherosclerosis, myocardial infarction, heart failure, arrhythmias, and stroke. Possible mechanisms include reduction in triglycerides, alteration in membrane fluidity, modulation of cardiac ion channels, and anti-inflammatory, anti-thrombotic, and anti-arrhythmic effects. Fish oil supplements are generally safe, and the risk of toxicity with methylmercury, an environmental toxin found in fish, is minimal. Current guidelines recommend the consumption of either one to two servings of oily fish per week or daily fish oil supplements (around 1 g of omega-3 polyunsaturated fatty acids per day) in adults. However, recent large-scale studies have failed to demonstrate any benefit of fish oil supplements on cardiovascular outcomes and mortality. Here, we review the different trials that evaluated the role of fish oil in cardiovascular diseases.

Reperfusion Changes AfterStroke and PracticalApproaches forNeuroprotection.

Reperfusion is the first line of care in a growing number of eligible acute ischemic stroke patients. Early reperfusion with thrombolytic drugs and endovascular mechanical devices is associated with improved outcome and lower mortality rates compared with natural history. Reperfusion is not without risk, however, and may result in reperfusion injury, which manifests in hemorrhagic transformation, brain edema, infarct progression, and neurologic worsening. In this article, the functional and structural changes and underlying molecular mechanisms of ischemia and reperfusion are reviewed. The pathways that lead to reperfusion injury and novel neuroprotective strategies with endogenous properties are discussed.

GW29-e0457 Ultrasound targeted microbubbles destruction-mediating the Ang1 gene transfection can improve the left ventricular mechanical synchrony during the progression of myocardial infarction in canines

GW29-e0457 Ultrasound targeted microbubbles destruction-mediating the Ang1 gene transfection can improve the left ventricular mechanical synchrony during the progression of myocardial infarction in canines

Problems in Stem Cell Therapy for Cardiac Repair and Tissue Engineering Approaches Based on Graphene and Its Derivatives.

Today, coronary artery disease is still one of the most important causes of mortality despite advanced surgical methods, pharmacotherapies and organ transplantation. These treatment modalities are intended to prevent further progression of myocardial infarction and do not involve the repair of the damaged part. Therefore, stem cell therapy has emerged as a new approach for the treatment of coronary artery disease. However, there are some restrictions that limit the use of these cells for desired repair. The leading limitation is that newly formed cardiomyocytes do not provide electrical integrity with local cells. In this paper, we review the difficulties that limit the use of stem cell therapy in cardiac repair and emphasize the importance of the integration of stem cell with tissue scaffolds with conductivity. Furthermore, significance of using graphene scaffolds in cardiac tissue engineering is highlighted due to its conductivity features. Recently, the fabrication of tissue scaffoldings has made it possible to create a biomimetic cellular environment while providing a new approach to solving these problems in treatment. Especially, the integration of stem cell therapy with graphene-based tissue scaffolds with electrical conductivity, is one of the promising new strategies to turn the success of two approaches of tissue engineering into synergistic effect in cardiac repair. Literature analysis has demonstrated that there are some limitations in use of stem cell therapy for successful treatment of cardiac repair and graphene-based tissue engineering approaches which are promising to solve these problems in the near future.

The Role of Susceptibility Weighted Imaging (SWI) in Evaluation of Acute Stroke

Background and Objectives: SWI provides information about blood oxygenation levels in intracranial vessels. Prior reports have shown that SWI focusing on venous drainage can provide noninvasive information about the degree of brain perfusion in arterialischemic stroke. We aimed to evaluate the influence of the SWI venous signal pattern in predicting stroke evolution. Materials and Methods: a semiquantitative analysis of venous signal intensity on SWI and diffusion characteristics on DTI was performed in 2o adult patients with acute stroke of MCA vascular territories. The mismatch between areas with SWI-hypointense venous signal and restricted diffusion was correlated with stroke progression on follow-up. Results: we included 2O patients with a confirmed diagnosis of arterial ischemic stroke. Follow-up images were available for. MCA stroke progression on follow-up was observed in 11/12 patient with DWI -SWI mismatch. Initial SWI hypointense venous signal and areas of restricted diffusion on DTI. This mismatch showed a statistically significant association (P _ 0.00188) for infarct progression. Conclusion: SWI-DWI mismatch predicts stroke progression in arterial ischemic stroke.

The Role of Susceptibility Weighted Imaging (SWI) in Evaluation of Acute Stroke

Background and Objectives: SWI provides information about blood oxygenation levels in intracranial vessels. Prior reports have shown that SWI focusing on venous drainage can provide noninvasive information about the degree of brain perfusion in arterialischemic stroke. We aimed to evaluate the influence of the SWI venous signal pattern in predicting stroke evolution. Materials and Methods: a semiquantitative analysis of venous signal intensity on SWI and diffusion characteristics on DTI was performed in 2o adult patients with acute stroke of MCA vascular territories. The mismatch between areas with SWI-hypointense venous signal and restricted diffusion was correlated with stroke progression on follow-up. Results: we included 2O patients with a confirmed diagnosis of arterial ischemic stroke. Follow-up images were available for. MCA stroke progression on follow-up was observed in 11/12 patient with DWI -SWI mismatch. Initial SWI hypointense venous signal and areas of restricted diffusion on DTI. This mismatch showed a statistically significant association (P _ 0.00188) for infarct progression. Conclusion: SWI-DWI mismatch predicts stroke progression in arterial ischemic stroke.