Effects of Extreme Temperatures on Cause-Specific Cardiovascular Mortality in China.

PubMed

Wang, Xuying; Li, Guoxing; Liu, Liqun; Westerdahl, Dane; Jin, Xiaobin; Pan, Xiaochuan

2015-12-21

Limited evidence is available for the effects of extreme temperatures on cause-specific cardiovascular mortality in China. We collected data from Beijing and Shanghai, China, during 2007-2009, including the daily mortality of cardiovascular disease, cerebrovascular disease, ischemic heart disease and hypertensive disease, as well as air pollution concentrations and weather conditions. We used Poisson regression with a distributed lag non-linear model to examine the effects of extremely high and low ambient temperatures on cause-specific cardiovascular mortality. For all cause-specific cardiovascular mortality, Beijing had stronger cold and hot effects than those in Shanghai. The cold effects on cause-specific cardiovascular mortality reached the strongest at lag 0-27, while the hot effects reached the strongest at lag 0-14. The effects of extremely low and high temperatures differed by mortality types in the two cities. Hypertensive disease in Beijing was particularly susceptible to both extremely high and low temperatures; while for Shanghai, people with ischemic heart disease showed the greatest relative risk (RRs = 1.16, 95% CI: 1.03, 1.34) to extremely low temperature. People with hypertensive disease were particularly susceptible to extremely low and high temperatures in Beijing. People with ischemic heart disease in Shanghai showed greater susceptibility to extremely cold days.

Hot shot induction and reperfusion with a specific blocker of the es-ENT1 nucleoside transporter before and after hypothermic cardioplegia abolishes myocardial stunning in acutely ischemic hearts despite metabolic derangement: Hot shot drug delivery before hypothermic cardioplegia

PubMed Central

Abd-Elfattah, Anwar Saad; Tuchy, Gert E.; Jessen, Michael E.; Salter, David R.; Goldstein, Jacques P.; Brunsting, Louis A.; Wechsler, Andrew S.

2013-01-01

Objective Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)–sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. Methods Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 µM EHNA and 25 µM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. Results Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. Conclusions Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery. PMID:23422047

Potential etiopathogenesis of seventh day syndrome following living donor liver transplantation: ischemia of the graft?

PubMed

Lan, Xiang; Li, Bo; Wang, Xiao-Fei; Wei, Yong-Gang; Yan, Lu-Nan; Zhao, Ji-Chun

2010-02-01

Seventh-day syndrome (7DS) is an early serious complication following liver transplantation with a high mortality because of its unknown etiopathogenesis. This study aimed to analyze the potential etiopathogenesis of 7DS. A retrospective analysis of 98 consecutive living donor liver transplants performed from 2001 to 2007 at our center revealed that 5 patients had suffered from 7DS; their age, MELD score, portal vein inflow and other parameters were compared with those of the other recipients. The 5 patients showed common features: (a) initial uneventful recovery, and a dramatic rise of serum liver enzyme levels 1 to 2 weeks later; (b) decreased inflow in the portal vein accompanied by augmentation of serum creatinine and urea nitrogen level; and (c) serial liver biopsy findings of apoptosis and ischemic necrosis of hepatocytes. Four of the 5 patients died. Age, waiting time to transplantation, MELD score, operation time, cold ischemic time, portal interceptive time and diameter of the portal vein were not significantly different between the 2 groups, but a difference was found in the flow rate of the portal vein (t=3.234, P<0.001). The 5 patients suffered from a decreased portal vein inflow, ischemic liver necrosis, and renal failure. Hence, hypoperfusion of the liver graft was considered to be the etiopathogenesis of 7DS, for which, however sufficient evidence is lacking. More studies of 7DS are needed.

Classification and evaluation of the functional results of replanted parts of the hand at the Prince of Wales Hospital and the Prince of Wales Children's Hospital: 1984 to 1988.

PubMed

Milroy, B C; Sackelariou, R P; Lendvay, P G; Baldwin, M R; McGlynn, M

1991-01-01

This paper describes a simple method of classification and evaluation of the functional results of replanted and revascularized parts in the hand. The results are presented in graphic form and have been analyzed to correlate various factors: injured part, cause, and zone (level) of injury. The type of injury, ischemic time and age have been studied in more detail to determine their influence of the final functional result. The series contains 187 amputated and devascularized parts of the hand in 119 patients who have undergone surgery at the Prince of Wales Hospital from 1984 through 1988. The length of cold or warm ischemic times, up to 16 hours in this series, while not affecting survival of the amputated part, does adversely affect the functional result. The survival rate of replanted parts in children was significantly less favorable than in adults, but the functional results were uniformly superior.

Taste and Temperature in Swallowing Transit Time after Stroke

PubMed Central

Cola, Paula C.; Gatto, Ana R.; da Silva, Roberta G.; Spadotto, André A.; Ribeiro, Priscila W.; Schelp, Arthur O.; Carvalho, Lidia R.; Henry, Maria A.C.A.

2012-01-01

Background Oropharyngeal dysphagia is common in individuals after stroke. Taste and temperature are used in dysphagia rehabilitation. The influence of stimuli, such as taste and temperature, on swallowing biomechanics has been investigated in both healthy individuals and in individuals with neurological disease. However, some questions still remain unanswered, such as how the sequence of offered stimuli influences the pharyngeal response. The goal of the present study was to determine the influence of the sequence of stimuli, sour taste and cold temperature, on pharyngeal transit time during deglutition in individuals after stroke. Methods The study included 60 individuals with unilateral ischemic stroke, 29 males and 31 females, aged 41–88 years (mean age: 66.2 years) examined 0–50 days after ictus (median: 6 days), with mild to moderate oropharyngeal dysphagia. Exclusion criteria were hemorrhagic stroke patients, patients with decreased level of consciousness, and clinically unstable patients, as confirmed by medical evaluation. The individuals were divided into two groups of 30 individuals each. Group 1 received a nonrandomized sequence of stimuli (i.e. natural, cold, sour, and sour-cold) and group 2 received a randomized sequence of stimuli. A videofluoroscopic swallowing study was performed to analyze the pharyngeal transit time. Four different stimuli (natural, cold, sour, and sour-cold) were offered. The images were digitalized and specific software was used to measure the pharyngeal transit time. Since the values did not present regular distribution and uniform variances, nonparametric tests were performed. Results Individuals in group 1 presented a significantly shorter pharyngeal transit time with the sour-cold stimulus than with the other stimuli. Individuals in group 2 did not show a significant difference in pharyngeal transit time between stimuli. Conclusions The results showed that the sequence of offered stimuli influences the pharyngeal transit time in a different way in individuals after stroke and suggest that, when the sour-cold stimulus is offered in a randomized sequence, it can influence the response to the other stimuli in stroke patients. Hence, the sour-cold stimulus could be used as a therapeutic aid in dysphagic stroke patients. PMID:23139681

State-of the-art review on the renal and visceral protection during open thoracoabdominal aortic aneurysm repair.

PubMed

Waked, Karl; Schepens, Marc

2018-01-01

During open thoracoabdominal aortic aneurysm repair (OTAAAR), there is an inevitable organ ischemic period that occurs when the abdominal arteries are being reattached to the aortic graft. Despite various protective techniques, the incidence of renal and visceral complications remains substantial. This state-of-the-art review gives an overview of the current and most evidence-based organ protection methods during OTAAAR, based on the most recent publications and personal experience. An electronic search was performed in four medical databases, using the following MeSH terms: thoracoabdominal aneurysm, TAAAR, visceral protection, renal protection, kidney, perfusion, and intestines. Every publication type was considered. The literature search was ended on August 31st, 2017. The left heart bypass (LHB) is currently the most frequent adjunct to provide distal aortic perfusion (DAP) during aortic clamping. Together with systemic hypothermia, it forms the cornerstone in organ protection during aortic clamping. Further renal protection can be obtained by selective renal perfusion (SRP) with cold blood or cold crystalloid solution, the latter enriched with mannitol. The perfusion should be administered in a volume- and pressure-controlled way and, if possible, by use of a pulsatile pump. Selective visceral perfusion (SVP) is not routinely used, as it does not provide adequate blood flow for visceral protection. The best way to protect the intestines is by minimizing the ischemic time. The preservation of renal and visceral function after OTAAAR can only be obtained with specific strategies before, during, and after the operation. This involves a series of measures, including selective digestive decontamination (SDD), avoidance of nephrotoxic drugs, minimizing the renal and intestinal ischemic time, systemic cooling, avoidance of hemodynamic instability, and regional protective perfusion of the kidneys. Future innovations in catheters, cardiac bypass flow types, mechanical components, hybrid vascular grafts, and pharmaceutical protection measures will hopefully further reduce organ complications.

Influence of Cold Ischemia Time in Combination with Donor Acute Kidney Injury on Kidney Transplantation Outcomes.

PubMed

Xia, Yu; Friedmann, Patricia; Cortes, Carlos M; Lubetzky, Michelle L; Kayler, Liise K

2015-08-01

Deceased-donor kidneys are often exposed to ischemic events from donor instability, as evidenced by acute kidney injury (AKI). Clinicians may be reluctant to transplant kidneys with AKI that also have prolonged cold ischemia time (CIT) for fear of an additional deleterious effect. We evaluated national data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys from donors with AKI (terminal serum creatinine ≥ 2 mg/dL), in which the CIT difference between recipients was ≥1, 5, 10, or 15 hours. On multivariate analysis of AKI kidney recipients, overall death-censored graft survival (DCGS) was comparable between recipients with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was at least 1 hour (adjusted hazard ratio [aHR] 0.98, 95% CI 0.85 to 1.13, n = 4,458), 5 hours (aHR 0.97, 95% CI 0.79 to 1.18, n = 2,412), 10 hours (aHR 0.82, 95% CI 0.59 to 1.15, n = 922), or 15 hours (aHR 0.94, 95% CI 0.57 to 1.58, n = 442). Overall patient survival of the longer CIT groups was comparable or protective with delta CIT of ≥1 (aHR 0.94, 95% CI 0.83 to 1.06), 5 (aHR 0.80, 95% CI 0.68 to 0.94), 10 (aHR 0.70, 95% CI 0.53 to 0.91), and 15 (aHR 0.64, 95%CI 0.43 to 0.95) hours. Between each of the 4 delta-CIT levels of shorter and longer CIT, there were no statistically significant differences in the proportion of acute rejection at delta ≥1, 5, 10, or 15 hours. These results suggest that in the setting of a previous ischemic donor event, prolonged CIT has limited bearing on long-term outcomes. This may be important evidence that despite the occurrence of other ischemic events, kidneys with prolonged CIT offer acceptable outcomes to recipients and are a potential source to expand the donor pool. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

The effect of the Statewide Sharing variance on geographic disparity in kidney transplantation in the United States.

PubMed

Davis, Ashley E; Mehrotra, Sanjay; Kilambi, Vikram; Kang, Joseph; McElroy, Lisa; Lapin, Brittany; Holl, Jane; Abecassis, Michael; Friedewald, John J; Ladner, Daniela P

2014-08-07

The Statewide Sharing variance to the national kidney allocation policy allocates kidneys not used within the procuring donor service area (DSA), first within the state, before the kidneys are offered regionally and nationally. Tennessee and Florida implemented this variance. Known geographic differences exist between the 58 DSAs, in direct violation of the Final Rule stipulated by the US Department of Health and Human Services. This study examined the effect of Statewide Sharing on geographic allocation disparity over time between DSAs within Tennessee and Florida and compared them with geographic disparity between the DSAs within a state for all states with more than one DSA (California, New York, North Carolina, Ohio, Pennsylvania, Texas, and Wisconsin). A retrospective analysis from 1987 to 2009 was conducted using Organ Procurement and Transplant Network data. Five previously used indicators for geographic allocation disparity were applied: deceased-donor kidney transplant rates, waiting time to transplantation, cumulative dialysis time at transplantation, 5-year graft survival, and cold ischemic time. Transplant rates, waiting time, dialysis time, and graft survival varied greatly between deceased-donor kidney recipients in DSAs in all states in 1987. After implementation of Statewide Sharing in 1992, disparity indicators decreased by 41%, 36%, 31%, and 9%, respectively, in Tennessee and by 28%, 62%, 34%, and 19%, respectively in Florida, such that the geographic allocation disparity in Tennessee and Florida almost completely disappeared. Statewide kidney allocations incurred 7.5 and 5 fewer hours of cold ischemic time in Tennessee and Florida, respectively. Geographic disparity between DSAs in all the other states worsened or improved to a lesser degree. As sweeping changes to the kidney allocation system are being discussed to alleviate geographic disparity--changes that are untested run the risk of unintended consequences--more limited changes, such as Statewide Sharing, should be further studied and considered. Copyright © 2014 by the American Society of Nephrology.

Optimization of Perioperative Conditions to Prevent Ischemic Cholangiopathy in Donation After Circulatory Death Donor Liver Transplantation.

PubMed

Kubal, Chandrashekhar; Mangus, Richard; Fridell, Jonathan; Saxena, Romil; Rush, Natalia; Wingler, Matthew; Ekser, Burcin; Tector, Joseph

2016-08-01

Donation after circulatory death (DCD) donor pool remains underutilized for liver transplantation (LT). We describe optimizing "modifiable risk factors," such as cold ischemia time (CIT) recipient warm ischemia time (WIT) and the use of thrombolytic flush at the time of procurement to minimize ischemic cholangiopathy (IC). From July 2011 (era II), to improve outcomes after DCD LT, measures were taken to minimize CIT, operative time and recipient WIT along with the use of tissue plasminogen activator (tPA) flush during DCD procurements. Thirty consecutive DCD LTs were performed prospectively in era II. Outcomes were compared with 61 historic controls (era I). Reperfusion biopsies were evaluated for the presence of necrosis and biliary epithelial damage. Median CIT (4.9 [3.5-5.9] vs 6.4 [4.3-12]; P < 0.001), hepatectomy time (70 [42-120] vs 81 [58-207]; P = 0.02), and recipient WIT (16 [13-31] vs 24[15-40]; P < 0.001) were significantly shorter in era II. All patients in era II received tPA flushed liver grafts. None of the patients in era II developed IC (0% vs 18%; P = 0.013). There were fewer biliary complications in era II, and there was no increased risk of bleeding associated with the use of tPA. One-year graft survival was slightly better in era II (n = 24 patients with 1 year follow-up) (88% vs 80%; P = 0.14). Optimizing peritransplant conditions, such as shortening ischemic times with the use of thrombolytic donor flush, may prevent IC after DCD LT. With this approach, the DCD donor pool may be expanded.

Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

PubMed

Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

2009-07-01

Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

Use and Outcomes of Kidneys from Donation after Circulatory Death Donors in the United States.

PubMed

Gill, John; Rose, Caren; Lesage, Julie; Joffres, Yayuk; Gill, Jagbir; O'Connor, Kevin

2017-12-01

Donation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country's 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10-26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area-level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes. Copyright © 2017 by the American Society of Nephrology.

Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women

PubMed Central

Grewen, Karen M.; Light, Kathleen C.; Mechlin, Beth; Girdler, Susan S.

2015-01-01

It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance. Objectives The purpose of this study was to examine the relationship between plasma oxytocin (OT) and pain sensitivity and to explore the relation of OT to other factors known to influence pain perception. Design OT concentration and sensitivity to ischemic, cold pressor, and thermal pain tasks were assessed in African American (n=25) and non-Hispanic White (n=23) pre-menopausal women. Results African American women demonstrated significantly lower pain tolerance across tasks compared with Whites (F1,46 =6.31, p=0.0156) and also exhibited lower plasma OT levels (AA: 3.90, W: 7.05 pg/mL; p=0.0014). Greater OT levels were correlated with greater tolerance to ischemic pain (r=0.36, p=0.013) and accounted for a marginally significant portion of the ethnic difference in ischemic pain tolerance (B=+0.29, p=0.06). Greater OT was also correlated with greater tolerance of cold pressor pain (r=0.31, p=0.03); however, this association was no longer seen after the variance due to ethnicity was accounted for. Conclusion These data suggest that reduced oxytocinergic function may be one of multiple biological factors contributing to the greater sensitivity to experimental ischemic pain, and to the greater burden of some types of clinical pain experienced by African Americans compared with Whites. PMID:18568974

Improving National Results in Liver Transplantation Using Grafts From Donation After Cardiac Death Donors.

PubMed

Croome, Kristopher P; Lee, David D; Keaveny, Andrew P; Taner, C Burcin

2016-12-01

Published reports describing the national experience with liver grafts from donation after cardiac death (DCD) donors have resulted in reservations with their widespread utilization. The present study aimed to investigate if temporal improvements in outcomes have been observed on a national level and to determine if donor and recipient selection have been modified in a fashion consistent with published data on DCD use in liver transplantation (LT). Patients undergoing DCD LT between 2003 and 2014 were obtained from the United Network of Organ Sharing Standard Transplant Analysis and Research file and divided into 3 equal eras based on the date of DCD LT: era 1 (2003-2006), era 2 (2007-2010), and era 3 (2011-2014). Improvement in graft survival was seen between era 1 and era 2 (P = 0.001) and between era 2 and era 3 (P < 0.001). Concurrently, an increase in the proportion of patients with hepatocellular carcinoma and a decrease in critically ill patients, retransplant recipients, donor age, warm ischemia time greater than 30 minutes and cold ischemic time also occurred over the same period. On multivariate analysis, significant predictors of graft survival included: recipient age, biologic MELD score, recipient on ventilator, recipient hepatitis C virus + serology, donor age and cold ischemic time. In addition, even after adjustment for all of the aforementioned variables, both era 2 (hazard ratio, 0.81; confidence interval, 0.69-0.94; P = 0.007), and era 3 (hazard ratio, 0.61; confidence interval, 0.5-0.73; P < 0.001) had a protective effect compared to era 1. The national outcomes for DCD LT have improved over the last 12 years. This change was associated with modifications in both recipient and donor selection. Furthermore, an era effect was observed, even after adjustment for all recipient and donor variables on multivariate analysis.

Serum Sodium and Potassium Levels in Cerebro-vascular Accident Patients.

PubMed

Farahmand, Farahmand; Choobi Anzali, Babak; Heshmat, Ramin; Ghafouri, Hamed-Basir; Hamedanchi, Sepehr

2013-05-01

We aim to assess serum sodium and potassium levels in patients with different types of cerebro-vascular accidents (CVA) in comparison to control group. A comparative cross-sectional study conducted on patients admitted to the emergency department from January to August 2012. Control group consisted of patients admitted to emergency department due to common cold, urinary tract infection, low back pain, cluster, and tension headache or migraine. Serum sodium and potassium levels were measured via standard laboratory methods. There were 77 patients in control group and 78 in CVA group. Forty nine patients from the CVA group had ischemic CVA, 11 had hemorrhagic CVA and 18 suffered a transient ischemic attack (TIA). Serum sodium level in control group was significantly lower than in patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). Serum potassium level in control group was higher than patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). Patients with hemorrhagic CVA showed significantly lower serum potassium level than patients with TIA and ischemic CVA (P < 0.001). Correspondingly, it was observed that serum sodium to potassium ratio was higher in patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). In patients with hemorrhagic CVA serum sodium to potassium ratio was higher when compared to patients with TIA and ischemic CVA (P < 0.001). This study shows that higher serum sodium and lower serum potassium level may be associated with higher incidence of CVA. Further studies are paramount to elucidate the role of serum electrolyte levels in vascular events.

The Siblings With Ischemic Stroke Study (SWISS) Protocol

PubMed Central

Meschia, James F; Brown, Robert D; Brott, Thomas G; Chukwudelunzu, Felix E; Hardy, John; Rich, Stephen S

2002-01-01

Background Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. Methods Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. Discussion Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members. PMID:11882254

Liver free fatty acid (FFA) accumulation as an indicator of ischemic injury during cold preservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemoto, E.M.; Kang, Y.; DeWolf, A.M.

1987-05-01

Reliable assessment of hepatic viability prior to harvest and transplant could improve graft success and aid in evaluating the efficacy of liver preservation techniques. Hepatic tissue metabolites, protein (Pr) synthesis, and ATP have been studied, but none reliably correlate with hepatic viability. Therefore, they studied changes in liver FFA relative to changes in ATP and Pr synthesis during cold ischemic preservation. Rats mechanically ventilated on 0.5% isoflurane/70% N/sub 2/O/30% O/sub 2/ were heparinized and their livers perfused with air-equilibrated Euro-Collins solution (ECS) at 0-4/sup 0/C and kept on ice. A piece of the liver was removed after 0, 2, 6,more » 8, 12, 24, 36 and 48 h of preservation for ATP and FFA analysis. A portion of the liver was sliced (250 ..mu..m thick) and incubated in vitro for /sup 14/C-lysine incorporation in albumin. ATP, FFA and Pr synthesis were unchanged in the first 8 h, but markedly decreased between 8 and 12 h with little change thereafter. In contrast, between 8 and 48 h, arachidonic and stearic acids increased by 5 and 2-fold, respectively. Changes in ATP and Pr synthesis correlate with the empirically derived clinical maximum of 8 to 12 h preservation. FFA accumulation appears to reflect hepatic ischemic injury and may be a means of evaluating the quality of a donor liver.« less

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

PubMed Central

Herrero-Fresneda, Immaculada; Torras, Joan; Cruzado, Josep M.; Condom, Enric; Vidal, August; Riera, Marta; Lloberas, Nuria; Alsina, Jeroni; Grinyo, Josep M.

2003-01-01

This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-β1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. The association of both factors accelerates and aggravates the progression of experimental chronic allograft nephropathy. PMID:12507896

Renal PKC-ε deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-α-dependent inhibition of apoptosis and inflammation.

PubMed

Rong, Song; Hueper, Katja; Kirsch, Torsten; Greite, Robert; Klemann, Christian; Mengel, Michael; Meier, Matthias; Menne, Jan; Leitges, Michael; Susnik, Nathan; Meier, Martin; Haller, Hermann; Shushakova, Nelli; Gueler, Faikah

2014-09-15

Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery and transplantation. We investigated the effect of PKC-ε deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC-ε-deficient and wild type (WT) control mice were subjected to 35 min of renal pedicle clamping to induce AKI. PKC-ε deficiency was associated with a marked improvement in survival and an attenuated loss of kidney function. Furthermore, functional MRI experiments revealed better renal perfusion in PKC-ε-deficient mice than in WT mice one day after IRI. Acute tubular necrosis and neutrophil infiltration were markedly reduced in PKC-ε-deficient mice. To determine whether this resistance to ischemia-reperfusion injury resulted from changes in local renal cells or infiltrating leukocytes, we studied a life-supporting renal transplant model of ischemic graft injury. We transplanted kidneys from H(2b) PKC-ε-deficient mice (129/SV) and their corresponding WT littermates into major histocompatibility complex-incompatible H(2d) recipients (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time. Recipients of WT allografts developed severe renal failure and died within 10 days of transplantation. Recipients of PKC-ε-deficient allografts had better renal function and survival; they had less generation of ROS and upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide synthase, and TNF-α) and showed less tubular epithelial cell apoptosis and inflammation in their allografts. These data suggest that local renal PKC-ε expression mediates proapoptotic and proinflammatory signaling and that an inhibitor of PKC-ε signaling could be used to prevent hypoxia-induced AKI. Copyright © 2014 the American Physiological Society.

Management of priapism with a trial of exercise in the emergency department.

PubMed

Gravel, Jonathan; LeBlanc, Constance; Varner, Catherine

2018-03-16

Priapism is characterized by persistent penile erection in the absence of sexual arousal or desire that does not subside with orgasm. Although relatively uncommon, it is a genitourinary emergency that necessities prompt work-up and appropriate management, as there is a time-dependent relationship between total duration of erection and an increasing risk of permanent erectile dysfunction. Confirming the type of priapism is key to proper management, but the majority of cases presenting to the emergency department are ischemic in nature. Conservative management strategies for ischemic priapism are sparsely described in the literature but generally include ice pack application to the area, cold showers, masturbation and rarely, exercise. These strategies lack sound evidence, but the risks of attempting them are minimal as long as access to more definitive treatment is not delayed. Lower-limb exercise as a first-line treatment warrants further study in the undifferentiated emergency department priapism population. The case we present and discuss here illustrates the potential benefits of a trial of acute lower-limb exercise, specifically stair climbing, as a treatment for medication-induced priapism. If effective, this simple non-invasive management strategy may decrease the time to effective treatment, requires minimal resource utilization, and ultimately, avoids the need for more invasive treatment.

[Acute effect of daily mean temperature on ischemic heart disease mortality: a multivariable meta-analysis from 12 counties across Hubei Province, China].

PubMed

Zhang, Y Q; Yu, C H; Bao, J Z

2016-11-06

Objective: To evaluate the acute effects of daily mean temperature on ischemic heart disease (IHD) mortality in 12 counties across Hubei Province, China. Methods: We obtained the daily IHD mortality data and meteorological data of the 12 counties for 2009-2012. The distributed lag nonlinear model (DLNM) was used to estimate the community-specific association between mean temperature and IHD mortality. A multivariate meta-analysis was then applied to pool the community-specific relationship between temperature and IHD mortality, and the effects of cold and heat on mortality risk. Results: In 2009-2012, of the 6 702 012 people included in this study, 19 688 died of IHD. A daily average of 1.2 IHD deaths occurred in each community. The annual average mean temperature was 16.6 ℃ during the study period. A nonlinear temperature-IHD mortality relationship was observed for different cumulative lag days at the provincial level. The pooled heat effect was acute but attenuated within 2 days. In contrast, the cold effect was delayed and persisted for more than 2 weeks. Compared with a reference temperature (25 th percentile of mean temperature during the study period, P 25 ), the cold effect for P 10 of mean temperature was associated with IHD mortality, the RR (95% CI ) was 1.084 (1.008-1.167) at lag 0-14, and 1.149 (1.053-1.253) at lag 0-21. For the P 1 cold temperature, the mortality RR (95% CI ) values were 1.116 (0.975-1.276) and 1.220 (1.04-1.428), respectively. We found no significant association between high temperatures and IHD mortality in the present study at different lag days. Conclusion: In Hubei Province, low temperature was associated with increased IHD mortality risk, and cold effects lasted for several days; no significant effect of high temperature was observed.

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs.

PubMed

Khan, Jenna; Lieberman, Joshua A; Lockwood, Christina M

2017-05-01

microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Pre-analytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissue-based analysis, warm ischemic time should be <1 h; cold ischemic time (4 °C) <24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.

Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study.

PubMed

Conti, V R; Bertranou, E G; Blackstone, E H; Kirklin, J W; Digerness, S B

1978-11-01

Seventeen of 34 consecutive patients undergoing coronary artery bypass grafting were randomly assigned to one of two methods of myocardial preservation. With the cold cardioplegic method (Group A), a 4 degrees C. asanguineous solution with 30 mEq. of potassium per liter was infused into the aortic root for about 2 minutes immediately after aortic cross-clamping and again after about 45 minutes or when myocardial temperature rose above 19 degrees C. External cardiac cooling was provided by constant infusion of 4 degrees C. Ringer's solution into the pericardium. Seventeen patients were assigned to simple cardiac cooling by hypothermic systemic perfusion before aortic cross-clamping plus external cardiac cooling (Group B). Electromechanical activity ceased within 1 to 2 minutes in Group A but continued throughout the ischemic period in 14 patients in Group B. Myocardial temperature (mean for all observations) during aortic cross-clamping was 17.2 +/- 0.44 degrees C. In Group A and 24.0 +/- 0.70 degrees C. in Group B. Operating conditions were better in Group A. Card-ac function early postoperatively was good in both groups clinically and according to measurements, but only in the cold cardioplegic group (A) was cardiac index not adversely affected by longer cross-clamp time. Myocardial necrosis occurred in both groups but was probably less in the cold cardioplegic group. Thirteen patients (76 percent) in Group A had no electrocardiographic evidence of myocardial injury, compared with eight (47 percent) in Group B (p = 0.08). Eleven (65 percent of Group A had no or short-lived appearance of ceatine phosphokinase isoenzyme (CK-MB), compared with six (35 percent) of Group B (p = 0.08). Time-related CK-MB and SGOT mean levels were consistently lower in Group A.

Normothermic perfusion: a new paradigm for organ preservation.

PubMed

Brockmann, Jens; Reddy, Srikanth; Coussios, Constantin; Pigott, David; Guirriero, Dino; Hughes, David; Morovat, Alireza; Roy, Debabrata; Winter, Lucy; Friend, Peter J

2009-07-01

Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%-86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.

One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study.

PubMed

Bergström, Lisa; Irewall, Anna-Lotta; Söderström, Lars; Ögren, Joachim; Laurell, Katarina; Mooe, Thomas

2017-08-01

Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age >75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with β-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment. © 2017 American Heart Association, Inc.

Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

PubMed

Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

2008-06-01

Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type.

PubMed

Yotsu, Rie Roselyne; Pham, Ngoc Minh; Oe, Makoto; Nagase, Takeshi; Sanada, Hiromi; Hara, Hisao; Fukuda, Shoji; Fujitani, Junko; Yamamoto-Honda, Ritsuko; Kajio, Hiroshi; Noda, Mitsuhiko; Tamaki, Takeshi

2014-01-01

To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time. Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test. The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values. Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs. Copyright © 2014 Elsevier Inc. All rights reserved.

Endobronchial perfluorocarbon reduces inflammatory activity before and after lung transplantation in an animal experimental model.

PubMed

Forgiarini Junior, Luiz Alberto; Holand, Arthur Rodrigo Ronconi; Forgiarini, Luiz Felipe; da Rosa, Darlan Pase; Marroni, Norma Anair Possa; Cardoso, Paulo Francisco Guerreiro; Andrade, Cristiano Feijó

2013-01-01

The aim of this study was to evaluate the use of liquid perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess its role in pulmonary protection after transplantation. Seventy-two rat lungs were flushed with low-potassium dextran (LPD) solution and randomized into three main groups: control with LPD alone and experimental with 3 (PFC3) and 7 mL/kg (PFC7) of endobronchial PFC instilled just after harvest. Each group was divided into four subgroups according to preservation time (3, 6, 12, and 24 hours). Afterwards, we performed lung transplantation using rat lungs preserved for 12 hours with LPD alone or with 7 mL/kg of endobronchial PFC. There was a significant increase in oxidative stress in the control group at 6 h of cold ischemic time compared with the PFC3 and PFC7 groups. The apoptotic activity and NF-κB expression were significantly higher in the control group compared with the PFC groups at 3, 12, and 24 h of cold preservation. After transplantation, the NF-κB, iNOS, and nitrotyrosine expression as well as caspase 3 activity were significantly lower in the PFC groups. The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability.

The effects of profound hypothermia on pancreas ischemic injury: a new experimental model.

PubMed

Rocha-Santos, Vinicius; Ferro, Oscar Cavalcante; Pantanali, Carlos Andrés; Seixas, Marcel Povlovistsch; Pecora, Rafael Antonio Arruda; Pinheiro, Rafael Soares; Claro, Laura Carolina López; Abdo, Emílio Elias; Chaib, Eleazar; D'Albuquerque, Luiz Augusto Carneiro

2014-08-01

Pancreatic ischemia-reperfusion (IR) has a key role in pancreas surgery and transplantation. Most experimental models evaluate the normothermic phase of the IR. We proposed a hypothermic model of pancreas IR to evaluate the benefic effects of the cold ischemic phase. We performed a reproducible model of hypothermic pancreatic IR. The ischemia was induced in the pancreatic tail portion (1-hour ischemia, 4-hour reperfusion) in 36 Wistar rats. They are divided in 3 groups as follows: group 1 (control), sham; group 2, normothermic IR; and group 3, hypothermic IR. In group 3, the temperature was maintained as close to 4.5°C. After reperfusion, serum amylase and lipase levels, inflammatory mediators (tumor necrosis factor α, interleukin 6), and pancreas histology were evaluated. In pancreatic IR groups, amylase, cytokines, and histological damage were significantly increased when compared with group 1. In the group 3, we observed a significant decrease in tumor necrosis factor α (P = 0.004) and interleukin 6 (P = 0.001) when compared with group 2. We did not observe significant difference in amylase (P = 0.867), lipase (P = 0.993), and histology (P = 0.201). In our experimental model, we reproduced the cold phase of pancreas IR, and the pancreas hypothermia reduced the inflammatory mediators after reperfusion.

Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T cells

PubMed Central

Tsuda, Hidetoshi; Su, Charles A.; Tanaka, Toshiaki; Ayasoufi, Katayoun; Min, Booki; Valujskikh, Anna; Fairchild, Robert L.

2018-01-01

Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade–induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS). Endogenous memory CD4+ and CD8+ T cell activation is markedly increased within complete MHC-mismatched cardiac allografts subjected to prolonged versus minimal CIS, and the memory CD8+ T cells directly mediate CTLA-4Ig–resistant allograft rejection. Memory CD8+ T cell activation within allografts subjected to prolonged CIS requires memory CD4+ T cell stimulation of graft DCs to produce p40 homodimers, but not IL-12 p40/p35 heterodimers. Targeting p40 abrogates memory CD8+ T cell proliferation within the allografts and their ability to mediate CTLA-4Ig–resistant allograft rejection. These findings indicate a critical role for memory CD4+ T cell–graft DC interactions to increase the intensity of endogenous memory CD8+ T cell activation needed to mediate rejection of higher-risk allografts subjected to increased CIS. PMID:29467328

Leukocyte and platelet depletion improves blood flow and function in a renal transplant model.

PubMed

Yates, Phillip J; Hosgood, Sarah A; Nicholson, Michael L

2012-01-01

Donation after cardiac death (DCD) donors are an important source of organs for transplantation. Due to warm and cold ischemic injury, DCD kidneys undergo a significant reperfusion insult when transplanted. This is manifested clinically as a high incidence of delayed graft function (DGF) and primary non-function (PNF). The importance of leukocytes in the generation of reperfusion injury is pivotal. Using an ex vivo porcine model of kidney transplantation, the effects of reperfusion with leukocyte and platelet depleted blood (LDB) and whole blood (WB) on renal blood flow and function were compared. Hemodynamic measurements were recorded, and biochemical, hematological, and histologic samples taken at set time-points. Reperfusion with LDB improved renal blood flow significantly compared with WB reperfusion. In addition, there was a significant improvement in creatinine clearance and renal oxygen consumption, but not fractional excretion of sodium, acid-base homeostasis, urinary nitric oxide (NO), or 8-isoprostane levels. This study represents a good model for the initial reperfusion period in renal transplantation. Improvement in only some functional markers and neither urinary NO nor 8-isoprostane levels indicates that improved blood flow alone is not sufficient to reverse the severe ischemic insult endured by DCD kidneys. Copyright © 2012 Elsevier Inc. All rights reserved.

Muscle cooling delays activation of the muscle metaboreflex in humans.

PubMed

Ray, C A; Hume, K M; Gracey, K H; Mahoney, E T

1997-11-01

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

Apoptosis in fresh and cryopreserved cardiac valves of pig samples.

PubMed

Rendal Vázquez, M Esther; Díaz Román, T M; Rodríguez Cabarcos, M; Zavanella Botta, C; Domenech García, N; González Cuesta, M; Sánchez Dopico, M J; Pértega Díaz, S; Andión Núñez, C

2008-06-01

To analyse the influence of cold ischemic time (CIT) (2-24 h) and of cryopreservation (liquid phase) on the viability of the valvular fibroblasts and in the presence of apoptosis. Cardiac valves from 10 pigs were evaluated by anatomo-pathological study of the wall, muscle and leaflet. At the same time, the presence of cellular death due to apoptosis was investigated in two ways; directly on tissue by Apodetec system and by two-colour flow cytometry assay analyzing a suspension of fibroblast from valve leaflets using Anexina V and propidium iodure (PI). We established three groups of samples to compare different experimental conditions: 2 h of ischemia (group 1), 24 h of ischemia (group 2), and a programme of cryopreservation (-1 degrees C/min) after 2 h of ischemia, followed by storage in liquid nitrogen during a week and thawing was performed (group 3). The analysis of viabilities showed slight differences between all three groups. The results indicated CIT of 24 h undergoing more structural affectation than CIT of 2 h. Flow cytometry analysis did not show important differences between groups; however cryopreserved samples (group 3) slightly less viability and a higher percentage of death by apoptosis than group 1 and 2 using flow cytometry. Apoptosis was confirmed on tissue from all valves but mainly in samples of group 2 and group 3. In summary, the viability of the valves in the case of ischemic times of 2 h, 24 h or after cryopreservation/thawing differs slightly. The death of the cells is mainly mediated by necrosis and not by apoptosis.

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PubMed

Yossepowitch, Ofer; Eggener, Scott E; Serio, Angel; Huang, William C; Snyder, Mark E; Vickers, Andrew J; Russo, Paul

2006-10-01

The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Total donor ischemic time: relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients.

PubMed

Rodrigues, Warren; Carr, Michelle; Ridout, Deborah; Carter, Katherine; Hulme, Sara Louise; Simmonds, Jacob; Elliott, Martin; Hoskote, Aparna; Burch, Michael; Brown, Kate L

2011-11-01

Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Retrospective cohort review. Tertiary pediatric transplant center in the United Kingdom. Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood pressure, as well as more prolonged ventilation and intensive care unit and hospital stays post-orthotopic heart transplant, reflecting increased morbidity.

Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review.

PubMed

Lau, Kui Kai; Lovelock, Caroline E; Li, Linxin; Simoni, Michela; Gutnikov, Sergei; Küker, Wilhelm; Mak, Henry Ka Fung; Rothwell, Peter M

2018-06-01

In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke. In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors. Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P <0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden ( P trend =0.87), but the 5-year risk of ICH was steeply related ( P trend <0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden ( P trend =0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events ( P trend =0.007), the association with ICH was accounted for ( P trend <0.0001) by disabling/fatal events (≥5 microbleeds: 82% disabling/fatal ICH versus 40% disabling/fatal ischemic stroke; P =0.035). In white and Chinese patients with ≥5 microbleeds, withholding antiplatelet drugs during the first year after transient ischemic attack/ischemic stroke may be inappropriate. However, the risk of ICH may outweigh any benefit thereafter. © 2018 The Authors.

Time Is Brain: The Stroke Theory of Relativity.

PubMed

Gomez, Camilo R

2018-04-25

Since the introduction of the philosophical tenet "Time is Brain!," multiple lines of research have demonstrated that other factors contribute to the degree of ischemic injury at any one point in time, and it is now clear that the therapeutic window of acute ischemic stroke is more protracted than it was first suspected. To define a more realistic relationship between time and the ischemic process, we used computational modeling to assess how these 2 variables are affected by collateral circulatory competence. Starting from the premise that the expression "Time=Brain" is mathematically false, we reviewed the existing literature on the attributes of cerebral ischemia over time, with particular attention to relevant clinical parameters, and the effect of different variables, particularly collateral circulation, on the time-ischemia relationship. We used this information to construct a theoretical computational model and applied it to categorically different yet abnormal cerebral perfusion scenarios, allowing comparison of their behavior both overall (i.e., final infarct volume) and in real-time (i.e., instantaneous infarct growth rate). Optimal collateral circulatory competence was predictably associated with slower infarct growth rates and prolongation of therapeutic window. Modeling of identifiable specific types of perfusion maps allows forecasting of the fate of the ischemic process over time. Distinct cerebral perfusion map patterns can be readily identified in patients with acute ischemic stroke. These patterns have inherently different behaviors relative to the time-ischemia construct, allowing the possibility of improving parsing and treatment allocation. It is clearly evident that the effect of time on the ischemic process is relative. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Scanning Electron Microscopy Findings of Machine Perfused Liver Graft After Warm Ischemia Between Hypothermic and Rewarming Machine Perfusion in Pigs.

PubMed

Meng, L; Matsuno, N; Watanabe, K; Furukori, M; Obara, H; Bochimoto, H; Watanabe, T; Fukukawa, H

2016-09-01

The shortage of organ donors is a universal problem. Use of grafts from donors after cardiac death would greatly contribute to the expansion of the donor organ pool. The two major methods of preservation are cold storage and machine perfusion (MP) preservation, and each has its own advantages. Several studies have reported the relative merits of MP for the preservation for grafts from donors after cardiac death. In this study, we used scanning electron microscopy (SEM) to assess the damage to the liver between hypothermic and rewarming preservation conditions. Porcine livers were perfused with a newly developed MP system. The livers were perfused for 4 hours with a modified University of Wisconsin solution-gluconate solution. In group 1, grafts were preserved with warm ischemic time for 60 minutes and hypothermic machine perfusion (HMP) for 4 hours. In group 2, grafts were preserved with warn ischemic time for 60 minutes and had rewarming up to 22°C by MP (RMP) for 4 hours. A significant enlargement of the mitochondria were observed in both the HMP and RMP groups under higher magnification, Additionally, vacuoles appeared occasionally in hepatocytes in the RMP for 4 hours group, but not in the HMP for 4 hours group. An analysis by scanning electron microscope appears to be useful to evaluate the levels of damage of hepatocytes compared with transmission electron microscopy, and further study is needed to analyze the significance of the appearance of swelling of mitochondria and vacuolization during preservation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Temporal trends in incidence of myocardial infarction and ischemic stroke by socioeconomic position in Sweden 1987-2010.

PubMed

Malki, Ninoa; Koupil, Ilona; Eloranta, Sandra; Weibull, Caroline E; Tiikkaja, Sanna; Ingelsson, Erik; Sparén, Pär

2014-01-01

We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2-1.4) in 1997 to 1.5 (1.4-1.7) in 2010 among men, and from 1.4 (1.3-1.6) in 1997 to 2.1 (1.8-2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

Delayed Post-ischemic Conditioning Significantly Improves the Outcome after Retinal Ischemia

PubMed Central

Dreixler, John C.; Poston, Jacqueline N.; Shaikh, Afzhal R.; Alexander, Michael; Tupper, Kelsey Y.; Marcet, Marcus M.; Bernaudin, Myriam; Roth, Steven

2011-01-01

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within one hour) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 minutes of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia. PMID:21501608

Comparative efficacy of Belzer or Euro-Collins solutions for pancreatic preservation during cold ischemic storage in rats.

PubMed

Perez, Rogério Renato; Goldenberg, Alberto; Netto, Alcides Augusto Salzedas; Gonzalez, Adriano Miziara

2014-03-01

To compare the efficacy of different types of solutions (Belzer or Euro-Collins) for the preservation of rat pancreas during cold ischemia. Thirty Wistar rats were divided into three groups according to the perfusion or storage solution: Group E (perfusion and storage in Euro-Collins solution); Group B (perfusion and storage in Belzer solution) and Group BE (Perfusion in Belzer solution and storage in Euro-Collins solution). After perfusion, the pancreas was excised and stored at 4˚C for 18 hours. Amylase was measured at 6, 12 and 18h, and histological analysis of the pancreas was performed after 18h of cold storage. Amylase was elevated and comparable in Groups E and BE after 12 and 18 hours of ischemia (p<0.05). In the exocrine pancreas, histological differences in the amount of necrosis (p=0.049), lymphocytic infiltrate (p<0.001) and neutrophilic infiltrate (p=0.004) were observed, with more favorable features present in Group B. In the endocrine pancreas, Group B showed less edema (p<0.001), but other parameters were similar among all groups. The Euro-Collins solution is inferior to the Belzer solution for the preservation of rat pancreas during cold ischemia.

Impacts of cold weather on all-cause and cause-specific mortality in Texas, 1990-2011.

PubMed

Chen, Tsun-Hsuan; Li, Xiao; Zhao, Jing; Zhang, Kai

2017-06-01

Cold weather was estimated to account for more than half of weather-related deaths in the U.S. during 2006-2010. Studies have shown that cold-related excessive mortality is especially relevant with decreasing latitude or in regions with mild winter. However, only limited studies have been conducted in the southern U.S. The purpose of our study is to examine impacts of cold weather on mortality in 12 major Texas Metropolitan Areas (MSAs) for the 22-year period, 1990-2011. Our study used a two-stage approach to examine the cold-mortality association. We first applied distributed lag non-linear models (DLNM) to 12 major MSAs to estimate cold effects for each area. A random effects meta-analysis was then used to estimate pooled effects. Age-stratified and cause-specific mortalities were modeled separately for each MSA. Most of the MSAs were associated with an increased risk in mortality ranging from 0.1% to 5.0% with a 1 °C decrease in temperature below the cold thresholds. Higher increased mortality risks were generally observed in MSAs with higher average daily mean temperatures and lower latitudes. Pooled effect estimate was 1.58% (95% Confidence Interval (CI) [0.81, 2.37]) increase in all-cause mortality risk with a 1 °C decrease in temperature. Cold wave effects in Texas were also examined, and several MSAs along the Texas Gulf Coast showed statistically significant cold wave-mortality associations. Effects of cold on all-cause mortality were highest among people over 75 years old (1.86%, 95% CI [1.09, 2.63]). Pooled estimates for cause-specific mortality were strongest in myocardial infarction (4.30%, 95% CI [1.18, 7.51]), followed by respiratory diseases (3.17%, 95% CI [0.26, 6.17]) and ischemic heart diseases (2.54%, 95% CI [1.08, 4.02]). In conclusion, cold weather generally increases mortality risk significantly in Texas, and the cold effects vary with MSAs, age groups, and cause-specific deaths. Copyright © 2017 Elsevier Ltd. All rights reserved.

An investigation of a hypothermic to ischemic ratio in patients following out-of-hospital cardiac arrest presenting with a shockable rhythm.

PubMed

Sawyer, Kelly N; Kurz, Michael C; Elswick, R K

2014-06-01

Targeted temperature management (TTM) improves outcome after out-of-hospital cardiac arrest (OHCA). We hypothesized that there may be a significant relationship between the dose of hypothermia, the time to return of spontaneous circulation (ROSC), and survival to discharge. Retrospective pilot investigation on 99 consecutive OHCA patients with initial shockable rhythm, surviving to admission, and undergoing TTM between 2008 and 2011. Dose of hypothermia was defined as the sum of the induction interval (time to target temperature [from ROSC to 33°C]); the controlled hypothermia interval (from reaching 33°C until rewarming); and the rewarming interval (from 33°C to 37°C). Time to ROSC was measured from pulselessness or 911 call time to ROSC. The ratio between the two was termed the hypothermic to ischemic ratio. Purposeful variable selection for logistic regression modeling was used to assess the influence of the hypothermic/ischemic ratio on survival. Odds ratios (OR) were used to examine the effects of predictor variables on survival. Of 99 patients, eight were excluded for deviation from protocol, death during protocol, or missing data. From the univariate models, survivors were more likely to be younger, have a shorter time to ROSC, and have a larger hypothermic/ischemic ratio. Survivors also had a nonsignificant trend toward a longer time to target temperature. In multivariable modeling, the hypothermic/ischemic ratio was the most significant predictor for survival (OR 2.161 [95% confidence interval 1.371, 3.404]). In this pilot study, the hypothermic to ischemic ratio was significantly associated with survival to discharge for patients with an initial shockable rhythm. Further investigation of the relationship between the dose of hypothermia and time to ROSC for postresuscitation TTM is needed.

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

PubMed

Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

PubMed

Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for brain penetration. This indicates that variables influencing brain penetration may not be limiting factors for use of piracetam in ischemic stroke.

The time dependence of the effect of ischemic preconditioning on successive sprint swimming performance.

PubMed

Lisbôa, Felipe D; Turnes, Tiago; Cruz, Rogério S O; Raimundo, João A G; Pereira, Gustavo S; Caputo, Fabrizio

2017-05-01

The present study aimed to determine the effects of ischemic preconditioning on performance in three successive 50-m swimming trials and to measure stroke rate, stroke length and blood lactate accumulation. Counterbalanced, repeated-measures cross-over study. On two separate days, eleven competitive male swimmers (20±3 years, 182±5cm, 77±5kg) performed three successive 50-m trials in a 50-m swimming pool, preceded by intermittent bilateral cuff inflation (4× 5-min of blood flow restriction+5-min of cuff deflation) at either 220 for thighs and 180mmHg for arms (ischemic preconditioning) or 20mmHg for both limbs (control-treatment). The 50-m trials were conducted 1-, 2-, and 8-h after the procedure. While no ergogenic effect of ischemic preconditioning was observed for 1-h (0.4%, 95% confidence limits of ±0.6%, p=0.215), there were clear beneficial effects of ischemic preconditioning on 2- and 8-h (1.0% and 1.2%, respectively; 95% confidence limits of ±0.6% in both cases, p≤0.002). Furthermore, ischemic preconditioning increased blood lactate accumulation in 2-(p<0.001) and 8-h (p=0.010) and stroke rate for 2- and 8-h in specific 10-m segments (p<0.05). These findings suggest a time-dependent effect of ischemic preconditioning on 50-m swimming performance for competitive athletes, with the time window of the beneficial effect starting after about 2-h and lasting for at least 8-h after ischemic preconditioning. This change in performance was accompanied by an increase in blood lactate accumulation and faster strokes in front crawl. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.

PubMed

Wetmore, James B; Mahnken, Jonathan D; Phadnis, Milind A

2016-09-21

Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis. We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified. Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved. Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.

Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors.

PubMed

Kayler, Liise; Yu, Xia; Cortes, Carlos; Lubetzky, Michelle; Friedmann, Patricia

2017-07-01

Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear of an additional deleterious effect. We performed a retrospective cohort study examining US registry data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys (derived from the same donor transplanted into different recipients) from DCD donors. On multivariable analysis, death-censored graft survival (DCGS) was comparable between recipients of kidneys with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5 hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer (aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66-1.99; n = 498). There was a higher rate of primary non function in the long CIT groups for delta 1 hour or longer (0.89% vs 1.63%; P = 0.006), 5 hours (1.09% vs 1.67%, P = 0.13); 10 hours (0.53% vs 1.78%; P = 0.03), and 15 hours (0.40% vs 1.61%; P = 0.18), respectively. Between each of the 4 delta CIT levels of shorter and longer CIT, there was a significantly and incrementally higher rate of delayed graft function in the long CIT groups for delta 1 hour or longer (37.3% vs 41.7%; P < 0.001), 5 hours (35.9% vs 42.7%; P < 0.001), 10 hours (29.4% vs 44.2%, P < 0.001), and 15 hours (29.6% vs 46.1%, P < 0.001), respectively. Overall patient survival was comparable with delta CITs of 1 hour or longer (aHR, 0.96; 95% CI, 0.84-1.08), 5 hours (aHR, 1.01; 95% CI, 0.85-1.20), and 15 hours (aHR, 1.27; 95% CI, 0.79-2.06) but not 10 hours (aHR, 1.47; 95% CI, 1.09-1.98). These results suggest that in the setting of a prior ischemic donor event, prolonged CIT has limited bearing on long-term outcomes.

Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors

PubMed Central

Kayler, Liise; Yu, Xia; Cortes, Carlos; Lubetzky, Michelle; Friedmann, Patricia

2017-01-01

Background Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear of an additional deleterious effect. Methods We performed a retrospective cohort study examining US registry data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys (derived from the same donor transplanted into different recipients) from DCD donors. Results On multivariable analysis, death-censored graft survival (DCGS) was comparable between recipients of kidneys with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5 hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer (aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66-1.99; n = 498). There was a higher rate of primary non function in the long CIT groups for delta 1 hour or longer (0.89% vs 1.63%; P = 0.006), 5 hours (1.09% vs 1.67%, P = 0.13); 10 hours (0.53% vs 1.78%; P = 0.03), and 15 hours (0.40% vs 1.61%; P = 0.18), respectively. Between each of the 4 delta CIT levels of shorter and longer CIT, there was a significantly and incrementally higher rate of delayed graft function in the long CIT groups for delta 1 hour or longer (37.3% vs 41.7%; P < 0.001), 5 hours (35.9% vs 42.7%; P < 0.001), 10 hours (29.4% vs 44.2%, P < 0.001), and 15 hours (29.6% vs 46.1%, P < 0.001), respectively. Overall patient survival was comparable with delta CITs of 1 hour or longer (aHR, 0.96; 95% CI, 0.84-1.08), 5 hours (aHR, 1.01; 95% CI, 0.85-1.20), and 15 hours (aHR, 1.27; 95% CI, 0.79-2.06) but not 10 hours (aHR, 1.47; 95% CI, 1.09-1.98). Conclusions These results suggest that in the setting of a prior ischemic donor event, prolonged CIT has limited bearing on long-term outcomes. PMID:28706980

A case of pediatric live-donor liver transplantation with a left lateral segment reduction by a linear stapler after reperfusion.

PubMed

Zenitani, Masahiro; Ueno, Takehisa; Nara, Keigo; Nakahata, Kengo; Uehara, Shuichiro; Soh, Hideki; Oue, Takaharu; Kondo, Hiroki; Nagano, Hiroaki; Usui, Noriaki

2014-09-01

In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre-operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post-operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Remote pre-procedural ischemic stroke as the greatest risk in carotid‑stenting‑associated stroke and death: a single center's experience.

PubMed

Rašiová, Mária; Špak, Ľubomír; Farkašová, Ľudmila; Pataky, Štefan; Koščo, Martin; Hudák, Marek; Moščovič, Matej; Leško, Norbert

2017-08-01

The goal of carotid artery stenting (CAS) is to decrease the stroke risk in patients with carotid stenosis. This procedure carries an immediate risk of stroke and death and many patients do not benefit from it, especially asymptomatic patients. It is crucial to accurately select the patients who would benefit from carotid procedure, and to rule out those for whom the procedure might be hazardous. Remote ischemic stroke is a known risk factor for stroke recurrence during surgery. The aim of our study was to determine the periprocedural complication risk (within 30 days after CAS) associated with carotid stenting (stroke, death) in patients with and without remote pre-procedural ischemic stroke, to analyze periprocedural risk in other specific patient subgroups treated with CAS, and to determine the impact of observed variables on all-cause mortality during long-term follow-up. We conducted a retrospective review of prospectively collected data from all patients treated with protected CAS between June 20, 2008 and December 31, 2015. Patient age, gender, type of carotid stenosis (symptomatic versus asymptomatic), side of stenosis (right or left carotid artery), type of cerebral protection (proximal versus distal), presence of comorbidities (remote ischemic pre-procedural ischemic stroke, coronary artery disease, diabetes mellitus, peripheral artery disease), previous ipsilateral carotid endarterectomy (CEA), contralateral carotid occlusion (CCO) and previous contralateral CAS/CEA were analyzed to identify higher CAS risk and to determine the impact of these variables on all-cause mortality during follow-up. Survival data were obtained from the Health Care Surveillance Authority registry. Mean follow-up was 1054 days (interquartile range 547.3; 1454.8). Remote pre-procedural ischemic stroke was defined as any-territory ischemic stroke >6 months prior to CAS. Primary periprocedural endpoint incidence (stroke/death) in 502 patients was 3.8% (N.=19) of all patients, 5.4% (N.=10) of symptomatic patients and 2.8% (N.=9) of asymptomatic patients. The risk of periprocedural stroke/death was 3.4 times higher in patients with (N.=198) compared to patients without remote ischemic stroke (N.=304) (6.6% versus 2.0% of patients without remote ischemic stroke; P=0.008). Periprocedural stroke/death in symptomatic patients (N.=186) was non-significantly higher in patients with remote ischemic stroke (N.=76) compared with patients without remote ischemic stroke (N.=110) (7.9% versus 3.6%; P=0.206). Asymptomatic patients with remote ischemic stroke (N.=122) had a 5.6-time-higher periprocedural risk of stroke/death compared with asymptomatic patients without remote ischemic stroke (N.=194) (5.7% versus 1.0%; P=0.014). Patients ≥75 years (N.=83) had a 3.0-time-higher periprocedural risk of stroke/death compared with younger patients (N.=419) (8.4% versus 2.9%; P=0.015); a non-significant increase of periprocedural stroke/death was found in both symptomatic (N.=35) and asymptomatic (N.=48) elderly patients (11.4% versus 4.0%, P=0.078; and 6.3% versus 2.4%, P=0.124, respectively). Increased periprocedural risk of stroke/death was not documented in other analyzed patient subgroups. During long-term follow-up, a 1.5-time-higher mortality risk was found in patients with remote ischemic stroke compared with patients without remote ischemic stroke in multivariable analysis; other patient subgroups (except older versus younger patients) did not differ in long-term mortality following carotid stenting. In our experience, all patients with remote pre-procedural any-territory ischemic stroke belong to risky subgroup for periprocedural stroke death after CAS. All asymptomatic patients with remote ischemic stroke should not be treated with CAS. Remote ischemic stroke increases all-cause mortality in long-term follow-up after carotid stenting. Patients aged ≥75 years also have increased risk of periprocedural stroke and death after CAS. These factors should help us to be more selective when planning carotid procedures.

Clinical Implications of Cluster Analysis-Based Classification of Acute Decompensated Heart Failure and Correlation with Bedside Hemodynamic Profiles.

PubMed

Ahmad, Tariq; Desai, Nihar; Wilson, Francis; Schulte, Phillip; Dunning, Allison; Jacoby, Daniel; Allen, Larry; Fiuzat, Mona; Rogers, Joseph; Felker, G Michael; O'Connor, Christopher; Patel, Chetan B

2016-01-01

Classification of acute decompensated heart failure (ADHF) is based on subjective criteria that crudely capture disease heterogeneity. Improved phenotyping of the syndrome may help improve therapeutic strategies. To derive cluster analysis-based groupings for patients hospitalized with ADHF, and compare their prognostic performance to hemodynamic classifications derived at the bedside. We performed a cluster analysis on baseline clinical variables and PAC measurements of 172 ADHF patients from the ESCAPE trial. Employing regression techniques, we examined associations between clusters and clinically determined hemodynamic profiles (warm/cold/wet/dry). We assessed association with clinical outcomes using Cox proportional hazards models. Likelihood ratio tests were used to compare the prognostic value of cluster data to that of hemodynamic data. We identified four advanced HF clusters: 1) male Caucasians with ischemic cardiomyopathy, multiple comorbidities, lowest B-type natriuretic peptide (BNP) levels; 2) females with non-ischemic cardiomyopathy, few comorbidities, most favorable hemodynamics; 3) young African American males with non-ischemic cardiomyopathy, most adverse hemodynamics, advanced disease; and 4) older Caucasians with ischemic cardiomyopathy, concomitant renal insufficiency, highest BNP levels. There was no association between clusters and bedside-derived hemodynamic profiles (p = 0.70). For all adverse clinical outcomes, Cluster 4 had the highest risk, and Cluster 2, the lowest. Compared to Cluster 4, Clusters 1-3 had 45-70% lower risk of all-cause mortality. Clusters were significantly associated with clinical outcomes, whereas hemodynamic profiles were not. By clustering patients with similar objective variables, we identified four clinically relevant phenotypes of ADHF patients, with no discernable relationship to hemodynamic profiles, but distinct associations with adverse outcomes. Our analysis suggests that ADHF classification using simultaneous considerations of etiology, comorbid conditions, and biomarker levels, may be superior to bedside classifications.

Proteomic analysis of endothelial cold-adaptation

PubMed Central

2011-01-01

Background Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h) and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. Results Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic) processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine-cysteine transulfuration pathway in increasing glutathione levels and the NAD salvage pathway in increasing the reducing capacity of cold-adapted cells. Conclusions Endothelial adaptation to mild-moderate hypothermia down-regulates anabolic processes and increases the reducing capacity of cells to enhance their resistance to oxidation and injury associated with 0°C storage and rewarming. Inducing these characteristics in a clinical setting could potentially limit the damaging effects of energy insufficiency due to ischemia and prevent the disruption of integrated metabolism at low temperatures. PMID:22192797

First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

PubMed

Dutkowski, Philipp; Polak, Wojciech G; Muiesan, Paolo; Schlegel, Andrea; Verhoeven, Cornelia J; Scalera, Irene; DeOliveira, Michelle L; Kron, Philipp; Clavien, Pierre-Alain

2015-11-01

Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.

[Understanding the reasons behind the low utilization of thrombolysis in hyperacute ischemic stroke].

PubMed

Zhang, Xiaoxue; Zhang, Jingfen; Li, Ruiming; Cheng, Guojuan; Chen, Qiang

2016-03-22

The study aimed to analyze the influencing factors of thrombolysis therapy in acute ischemic stroke patients with onset time less than 4.5 hours. We consecutively prospectively screened acute ischemic stroke patients with onset time less than 4.5 hours from emergency department, outpatients and inpatients of neurology department, and image center in our hospital over a 31-month time period (April 2012-November 2014). The rate of thrombolysis and the reasons for not receiving thrombolysis were analyzed. A total of 538 patients who met the inclusion criteria were included (68.2% males, mean age 67±13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons for the patients not receiving thrombolysis included minor symptoms (172 cases, 39.6%), rapidly improving symptoms and high possibility of transient ischemic attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44, 10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years old (38, 8.8%). The thrombolysis rate within time window of acute ischemic stroke is remarkably higher than that of several years ago in China. The main reasons for not receiving thrombolysis are minor and rapidly improving symptoms, patients or families' refusal, in-hospital delay, elderly people with age over than 80 years old.

Kidney donation after circulatory death in a country with a high number of brain dead donors: 10-year experience in Belgium.

PubMed

Jochmans, Ina; Darius, Tom; Kuypers, Dirk; Monbaliu, Diethard; Goffin, Eric; Mourad, Michel; Ledinh, Hieu; Weekers, Laurent; Peeters, Patrick; Randon, Caren; Bosmans, Jean-Louis; Roeyen, Geert; Abramowicz, Daniel; Hoang, Anh-Dung; De Pauw, Luc; Rahmel, Axel; Squifflet, Jean-Paul; Pirenne, Jacques

2012-08-01

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five-year patient/graft survival was assessed using Kaplan-Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five-year patient and death-censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine-tryptophan-ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

[CHANGING OF ISCHEMIC M. SOLEUS TETANIC CONTRACTION PARAMETERS IN RATS WITH CHRONIC ALCOHOL INTOXICATION].

PubMed

Melnychuk, O A; Motuziuk, O P; Shvayko, S Ye

2015-01-01

This article deals with the changes of isolated ischemic m. soleus tetanus parameters in rats with chronic alcohol intoxication. The experiments were carried out on 15 male Wistar rats that were divided into three groups for 5 animals in each: group I (control) and two groups in which was induced hind limbs acute muscles ischemia: group II - rats without alcoholic intoxication, group III - rats with chronic alcoholic intoxication. Strain measurement muscle mechanical activity were conducted in isometric mode under conditions of direct electrical muscular preparation stimulation. It is proved that ischemic m. soleus tetanic force in rats with chronic alcoholic intoxication in comparison with rats without alcoholic intoxication does not significant changes. But signifycantly increases the reaching tetanus peak time. It is shown that in rats without alcoholic intoxication and with chronic alcoholic intoxication in comparison with intact animals, significantly decreases the duration of ischemic m. soleus stabile force level. It is shoved significant changes of individual muscles contraction time course of ischemic m. soleus tetanus in this rats group in comparison to intact animal. It is shown that these changes influence on successive muscular contraction efficiency of frequency summation in ischemic m. soleus tetanus and their speed-power characteristics.

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

PubMed

Pham, Thai H; Melton, Shelby D; McLaren, Patrick J; Mokdad, Ali A; Huerta, Sergio; Wang, David H; Perry, Kyle A; Hardaker, Hope L; Dolan, James P

2017-09-01

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls. Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit. © 2017 Wiley Periodicals, Inc.

Fever control and application of hypothermia using intravenous cold saline

PubMed Central

Fink, Ericka L.; Kochanek, Patrick M.; Clark, Robert S. B.; Bell, Michael J.

2013-01-01

Objective To describe the use and feasibility of cold saline to decrease body temperature in pediatric neurocritical care. Design Retrospective chart review. Setting Pediatric tertiary care university hospital. Patients Children between 1 week and 17 yrs of age admitted to the pediatric intensive care unit with acute brain injury and having received intravenous cold saline between June-August 2009. Intervention(s) None. Measurements and Main Results Eighteen subjects accounted for 20 infusions with mean infusion volume 18 ± 10 cc/kg. Eight subjects had traumatic brain injury (TBI), 2 had intracranial hemorrhage, 6 had cardiac arrest, and one each had ischemic stroke and status epilepticus. The mean age was 9.5 ± 4.8 yrs. Temperature decreased from 38.7 ± 1.1°C to 37.7 ± 1.2°C and 37.0 ± 2.0 to 35.3 ± 1.6°C one h after infusion for fever (n=14, p<.05) or hypothermia (HT) induction (n=6, p=.05), respectively. Cold saline was not bolused, rather infused over 10–15 minutes. Mean arterial blood pressure and oxygenation parameters (PaO2/FiO2 ratio, mean airway pressure) were unchanged, but heart rate decreased in HT subjects (121 ± 4 vs. 109 ± 12; p<.05). Serum sodium concentration and International normalized ratio were significantly increased after cold saline infusion. There were no differences between pre- and post-infusion serum glucose and hematocrit, nor cerebral perfusion pressure or intracranial pressure in TBI patients. Conclusions Cold saline was an effective method of reducing temperature in children with acute brain injury. This approach can be considered to treat fever or to induce HT. Prospective study comparing safety and efficacy versus other cooling measures should be considered. PMID:21037507

First-aid with warm water delays burn progression and increases skin survival.

PubMed

Tobalem, M; Harder, Y; Tschanz, E; Speidel, V; Pittet-Cuénod, B; Wettstein, R

2013-02-01

First aid treatment for thermal injuries with cold water removes heat and decreases inflammation. However, perfusion in the ischemic zone surrounding the coagulated core can be compromised by cold-induced vasoconstriction and favor burn progression. The aim of this study is to evaluate the effect of local warming on burn progression in the rat comb burn model. 24 male Wistar rats were randomly assigned to either no treatment (control) or application of cold (17 °C) or warm (37 °C) water applied for 20 min. Evolution of burn depth, interspace necrosis, and microcirculatory perfusion were assessed with histology, planimetry, respectively with Laser Doppler flowmetry after 1 h, as well as 1, 4, and 7 days. Consistent conversion from a superficial to a deep dermal burn within 24 h was obtained in control animals. Warm and cold water significantly delayed burn depth progression, however after 4 days the burn depth was similar in all groups. Interspace necrosis was significantly reduced by warm water treatment (62±4% vs. 69±5% (cold water) and 82±3% (control); p<0.05). This was attributed to the significantly improved perfusion after warming, which was present 1 h after burn induction and was maintained thereafter (103±4% of baseline vs. 91±3% for cold water and 80±2% for control, p<0.05). In order to limit damage after burn injury, burn progression has to be prevented. Besides delaying burn progression, the application of warm water provided an additional benefit by improving the microcirculatory perfusion, which translated into increased tissue survival. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

New Approach to Identify Ischemic Stroke Patients at Risk to Develop Hemorrhagic Transformation

PubMed Central

MANOLESCU, Bogdan Nicolae; JICKLING, Glen C.

2012-01-01

ABSTRACT Some patients with ischemic stroke are subject to hemorrhagic transformation, a complication leading to increased patient morbidity and mortality. The discovery of biomarkers that can be used to identify ischemic strokes prone to this complication are very important for the clinical practice because therapy could be altered to mitigate the risk. We discuss here the results of a trial that evaluated for the first time tight junction proteins as biomarkers of blood-brain barrier disruption and hemorrhagic transformation in ischemic stroke. PMID:23482691

Use of a Diagnostic Score to Prioritize Computed Tomographic (CT) Imaging for Patients Suspected of Ischemic Stroke Who May Benefit from Thrombolytic Therapy

PubMed Central

Bots, Michiel L.; Selvarajah, Sharmini; Kappelle, L. Jaap; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Vaartjes, Ilonca

2016-01-01

Background A shortage of computed tomographic (CT) machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging. Methods From the Malaysian National Neurology Registry, we selected patients aged 18 years and over with clinical features suggesting of a stroke, who arrived in the hospital 4.5 hours or less from ictus. The prioritization of receiving CT imaging was left to the discretion of the treating physician. We applied the Siriraj Stroke Score to all patients, refitted the score and defined a cut-off value to best distinguish an ischemic stroke from a hemorrhagic stroke. Results Of the 2176 patients included, 73% had an ischemic stroke. Only 33% of the ischemic stroke patients had CT imaging within 4.5 hours. The median door-to-scan time for these patients was 4 hours (IQR: 1;16). With the recalibrated score, it would have been possible to prioritize 95% (95% CI: 94%–96%) of patients with an ischemic stroke for urgent CT imaging. Conclusions In settings where CT imaging capacity is limited, we propose the use of the Siriraj Stroke Score to prioritize patients with a probable ischemic stroke for urgent CT imaging. PMID:27768752

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events.

PubMed

Bavry, Anthony A; Elgendy, Islam Y; Elbez, Yedid; Mahmoud, Ahmed N; Sorbets, Emmanuel; Steg, Philippe Gabriel; Bhatt, Deepak L

2017-09-01

The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined. Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events. Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time-varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke. In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73-1.45, P = 0.86). In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event. © 2017 Wiley Periodicals, Inc.

1.4 times increase in atrial fibrillation-related ischemic stroke and TIA over 12years in a stroke center.

PubMed

Yang, Qiong; Churilov, Leonid; Fan, Dongsheng; Davis, Stephen; Yan, Bernard

2017-08-15

Prevalence of atrial fibrillation (AF) has quadrupled in the past 50years in the general population. However, there is uncertainty regarding prevalence of AF over time in ischemic stroke patients given the aging population and enhanced surveillance of AF. We aimed to explore the changing prevalence of AF as well as other risk factors, stroke subtypes, investigations and pre-stroke medications among ischemic stroke and transient ischemic attack (TIA) patients. We performed a retrospective analysis of data from a prospective database of consecutive patients with acute ischemic stroke and TIA from 2004 to 2015. Trends in risk factors and other variables year by year were analyzed using logistic regression or median regression. Among 6275 patients (median age [interquartile range] 74 [62-82] years, 56% males), the prevalence of AF increased 1.4 times over 12years (from 23.3% to 32.7%, P<0.001). The increase in the prevalence of AF remained significant after adjustment for age and the use of Holter monitoring. There was also a significant increase in prevalence of hypertension (67.4% to 77.3%), structural heart disease (9.8% to 10.5%), and previous TIA (10.9% to 13.7%) and a significant decrease in prevalence of dyslipidemia (71.8% to 49.4%). There was a 1.4 times increase in the prevalence of AF among consecutive ischemic stroke and TIA patients in the past 12years in a hospital-based registry. More active screening of the general population for AF may be warranted in order to decrease the overall stroke burden. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort.

PubMed

Goulart, Alessandra C; Fernandes, Tiotrefis G; Santos, Itamar S; Alencar, Airlane P; Bensenor, Isabela M; Lotufo, Paulo A

2013-05-24

Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from "The Study of Stroke Mortality and Morbidity" (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

Automatic assessment of dynamic contrast-enhanced MRI in an ischemic rat hindlimb model: an exploratory study of transplanted multipotent progenitor cells.

PubMed

Hsu, Li-Yueh; Wragg, Andrew; Anderson, Stasia A; Balaban, Robert S; Boehm, Manfred; Arai, Andrew E

2008-02-01

This study presents computerized automatic image analysis for quantitatively evaluating dynamic contrast-enhanced MRI in an ischemic rat hindlimb model. MRI at 7 T was performed on animals in a blinded placebo-controlled experiment comparing multipotent adult progenitor cell-derived progenitor cell (MDPC)-treated, phosphate buffered saline (PBS)-injected, and sham-operated rats. Ischemic and non-ischemic limb regions of interest were automatically segmented from time-series images for detecting changes in perfusion and late enhancement. In correlation analysis of the time-signal intensity histograms, the MDPC-treated limbs correlated well with their corresponding non-ischemic limbs. However, the correlation coefficient of the PBS control group was significantly lower than that of the MDPC-treated and sham-operated groups. In semi-quantitative parametric maps of contrast enhancement, there was no significant difference in hypo-enhanced area between the MDPC and PBS groups at early perfusion-dependent time frames. However, the late-enhancement area was significantly larger in the PBS than the MDPC group. The results of this exploratory study show that MDPC-treated rats could be objectively distinguished from PBS controls. The differences were primarily determined by late contrast enhancement of PBS-treated limbs. These computerized methods appear promising for assessing perfusion and late enhancement in dynamic contrast-enhanced MRI.

Impact of Smartphone Applications on Timing of Endovascular Therapy for Ischemic Stroke: A Preliminary Study.

PubMed

Alotaibi, Naif M; Sarzetto, Francesca; Guha, Daipayan; Lu, Michael; Bodo, Andre; Gupta, Shaurya; Dyer, Erin; Howard, Peter; da Costa, Leodante; Swartz, Richard H; Boyle, Karl; Nathens, Avery B; Yang, Victor X D

2017-11-01

The metrics of imaging-to-puncture and imaging-to-reperfusion were recently found to be associated with the clinical outcomes of endovascular thrombectomy for acute ischemic stroke. However, measures for improving workflow within hospitals to achieve better timing results are largely unexplored for endovascular therapy. The aim of this study was to examine our experience with a novel smartphone application developed in house to improve our timing metrics for endovascular treatment. We developed an encrypted smartphone application connecting all stroke team members to expedite conversations and to provide synchronized real-time updates on the time window from stroke onset to imaging and to puncture. The effects of the application on the timing of endovascular therapy were evaluated with a secondary analysis of our single-center cohort. Our primary outcome was imaging-to-puncture time. We assessed the outcomes with nonparametric tests of statistical significance. Forty-five patients met our criteria for analysis among 66 consecutive patients with acute ischemic stroke who received endovascular therapy at our institution. After the implementation of the smartphone application, imaging-to-puncture time was significantly reduced (preapplication median time, 127 minutes; postapplication time, 69 minutes; P < 0.001). Puncture-to-reperfusion time was not affected by the application use (42 minutes vs. 36 minutes). The use of smartphone applications may reduce treatment times for endovascular therapy in acute ischemic stroke. Further studies are needed to confirm our findings. Copyright © 2017. Published by Elsevier Inc.

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

PubMed

Rivera-Lara, Lucia; Murthy, Santosh B; Nekoovaght-Tak, Saman; Ali, Hasan; McBee, Nichol; Dlugash, Rachel; Ram, Malathi; Thompson, Richard; Awad, Issam A; Hanley, Daniel F; Ziai, Wendy C

2018-03-27

Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

C60 Fullerene as Promising Therapeutic Agent for the Prevention and Correction of Skeletal Muscle Functioning at Ischemic Injury

NASA Astrophysics Data System (ADS)

Nozdrenko, D. M.; Zavodovskyi, D. O.; Matvienko, T. Yu.; Zay, S. Yu.; Bogutska, K. I.; Prylutskyy, Yu. I.; Ritter, U.; Scharff, P.

2017-02-01

The therapeutic effect of pristine C60 fullerene aqueous colloid solution (C60FAS) on the functioning of the rat soleus muscle at ischemic injury depending on the time of the general pathogenesis of muscular system and method of administration C60FAS in vivo was investigated. It was found that intravenous administration of C60FAS is the optimal for correction of speed macroparameters of contraction for ischemic muscle damage. At the same time, intramuscular administration of C60FAS shows pronounced protective effect in movements associated with the generation of maximum force responses or prolonged contractions, which increase the muscle fatigue level. Analysis of content concentration of creatine phosphokinase and lactate dehydrogenase enzymes in the blood of experimental animals indicates directly that C60FAS may be a promising therapeutic agent for the prevention and correction of ischemic-damaged skeletal muscle function.

Magnetic resonance imaging spectrum of perinatal hypoxic-ischemic brain injury

PubMed Central

Varghese, Binoj; Xavier, Rose; Manoj, V C; Aneesh, M K; Priya, P S; Kumar, Ashok; Sreenivasan, V K

2016-01-01

Perinatal hypoxic–ischemic brain injury results in neonatal hypoxic–ischemic encephalopathy and serious long-term neurodevelopmental sequelae. Magnetic resonance imaging (MRI) of the brain is an ideal and safe imaging modality for suspected hypoxic–ischemic injury. The pattern of injury depends on brain maturity at the time of insult, severity of hypotension, and duration of insult. Time of imaging after the insult influences the imaging findings. Mild to moderate hypoperfusion results in germinal matrix hemorrhages and periventricular leukomalacia in preterm neonates and parasagittal watershed territory infarcts in full-term neonates. Severe insult preferentially damages the deep gray matter in both term and preterm infants. However, associated frequent perirolandic injury is seen in term neonates. MRI is useful in establishing the clinical diagnosis, assessing the severity of injury, and thereby prognosticating the outcome. Familiarity with imaging spectrum and insight into factors affecting the injury will enlighten the radiologist to provide an appropriate diagnosis. PMID:27857456

MRI Features in a Canine Model of Ischemic Stroke: Correlation between Lesion Volume and Neurobehavioral Status during the Subacute Stage

PubMed Central

Kang, Byeong-Teck; Jang, Dong-Pyo; Gu, Su-Hyun; Lee, Jong-Hwan; Jung, Dong-In; Lim, Chae-Young; Kim, Ha-Jung; Kim, Young-Bo; Kim, Hyung-Joong; Woo, Eung-Je; Cho, Zang-Hee; Park, Hee-Myung

2009-01-01

The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI) and assess the correlation between the volume of the ischemic lesion and neurobehavioral status during the subacute stage of ischemic stroke. Ischemic stroke was induced in 6 healthy laboratory beagles through permanent occlusion of the middle cerebral artery (MCAO). T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), measurement of the apparent diffusion coefficient (ADC) ratio, and neurobehavioral evaluation were performed 3 times serially by using a 1.5-T MR system: before and 3 and 10 d after MCAO. Ischemic lesions demonstrated T2 hyperintensity, FLAIR hyperintensity, and DWI hyperintensity. The ADC ratio was decreased initially but then was increased at 10 d after MCAO. Ischemic lesion volumes on T2-weighted and FLAIR imaging were not significantly different from those on DWI. The lesion volume and neurobehavioral score showed strong correlation. Our results suggest that conventional MRI may be a reliable diagnostic tool during the subacute stage of canine ischemic stroke. PMID:19887030

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Relationship of ischemic times and left atrial volume and function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilic, Ivan; Stankovic, Ivan; Vidakovic, Radosav; Jovanovic, Vladimir; Vlahovic Stipac, Alja; Putnikovic, BiIjana; Neskovic, Aleksandar N

2015-04-01

Little is known about the impact of duration of ischemia on left atrial (LA) volumes and function during acute phase of myocardial infarction. We investigated the relationship of ischemic times, echocardiographic indices of diastolic function and LA volumes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). A total of 433 consecutive STEMI patients underwent echocardiographic examination within 48 h of primary PCI, including the measurement of LA volumes and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'). Time intervals from onset of chest pain to hospital admission and reperfusion were collected and magnitude of Troponin I release was used to assess infarct size. Patients with LA volume index (LAVI) ≥28 ml/m(2) had longer total ischemic time (410 ± 347 vs. 303 ± 314 min, p = 0.007) and higher E/e' ratio (15 ± 5 vs. 10 ± 3, p < 0.001) than those with LAVI <28 ml/m(2), while the indices of LA function were similar between the study groups (p > 0.05, for all). Significant correlation was found between E/e' and LA volumes at all stages of LA filling and contraction (r = 0.363-0.434; p < 0.001, for all) while total ischemic time along with E/e' and restrictive filling pattern remained independent predictor of LA enlargement. Increased LA volume is associated with longer ischemic times and may be a sensitive marker of increased left ventricular filling pressures in STEMI patients treated with primary PCI.

[Effect of "Xingnao Kaiqiao Zhenfa" (Acupuncture Technique for Restoring Consciousness) Combined with Rehabilitation Training on Nerve Repair and Expression of Growth-associated Protein-43 of Peri-ischemic Cortex in Ischemic Stroke Rats].

PubMed

Xu, Lei; Yan, Xing-Zhou; Li, Zhen-Yu; Cao, Xiao-Fang; Wang, Min

2017-06-25

To observe the effect of "Xingnao Kaiqiao Zhenfa" (acupuncture technique for restoring consciousness) combined with enriched rehabilitation training on motor function and expression of growth-associated protein-43 (GAP-43) of peri-ischemic cortex in ischemic stroke rats, so as to investigate its mechanism underlying improvement of ischemic stroke. SD rats were randomly divided into sham operation, model, rehabilitation and comprehensive rehabilitation groups, which were further divided into 3 time-points:7, 14 and 21 d ( n =6 in each). Cerebral ischemia(CI) model was established by occlusion of the middle cerebral artery with heat-coagulation. The rehabilitation group was treated by enriched rehabilitation training, once a day. The comprehensive rehabilitation group was treated by acupuncture combined with enriched rehabilitation training. Acupuncture was applied to bilateral "Neiguan"(PC 6) and "Shuigou"(GV 26) for 30 min, once a day. The neurological function score, balance-beam walking test and rotating-rod walking test were evaluated at the end of the corresponding treatment time. The expression of GAP-43 in peri-ischemic cortex was detected by immunohistochemistry. In comparison with the sham operation group, the scores of neurological function, beam walking test and rotating-rod walking test were significantly higher in the model group ( P <0.01). There were no significant changes in the scores of balance-beam walking and rotating-rod walking tests in the rehabilitation group compared with the model group on day 7 ( P >0.05). Compared with the model group at the other time points, the scores of neurological function, balance-beam walking test and rotating-rod walking test were significantly lower in the rehabilitation and comprehensive rehabilitation groups ( P <0.05). Compared with the rehabilitation group, the scores of neurological function, balance-beam walking test and rotating-rod walking test were significantly lower in the comprehensive rehabilitation group ( P <0.05). In comparison with the sham operation group, the number of GAP-43 positive cells of peri-ischemic cortex was significantly higher in the model group ( P <0.01). Compared with the model group, the numbers of GAP-43 positive cells of peri-ischemic cortex were significantly increased in the rehabilitation and comprehensive rehabilitation groups ( P <0.01). The number of GAP-43 positive cells of peri-ischemic cortex in the comprehensive rehabilitation group was significantly higher than that in the rehabilitation group ( P <0.01). "Xingnao Kaiqiao Zhenfa" combined with enriched rehabilitation training can promote the recovery of nerve function in ischemic stroke rats, which may be associated with its effect in up-regulating the expression of GAP-43 in the peri-ischemic cortex.

[The impact of non-thrombolytic management of acute ischemic stroke in older individuals: the experience of the Federal District, Brazil].

PubMed

Moura, Mirian; Casulari, Luiz Augusto

2015-07-01

To analyze the impact of a non-specific, decentralized treatment protocol for ischemic stroke in older individuals on the quality of the care provided in the public health care system (SUS, Sistema Único de Saúde) in the Federal District. This retrospective historical control study employed data from the SUS Hospital Information System (SIH/SUS). Two time periods were compared: before and after the adoption of a protocol based on non-specific measures (medical therapy without alteplase) and decentralized care. A set of 2 369 admissions of patients older than 60 years with ischemic stroke was analyzed for the period of 2006/2007, and 5 207 admissions for 2010/2011. The variables were frequency, length of stay, mortality, lethality of ischemic stroke, intensive care unit (ICU) admission, and hospital reimbursement for ischemic stroke admissions. Effectiveness was evaluated based on mortality and lethality rates and efficiency was evaluated based on length of stay, use of ICU, and reimbursed amounts. In the second time period, there was an increase of 119.8% in the number of ischemic stroke admissions (P = 0.0001), increase of 27.3% in absolute mortality, decrease of 5.0% in lethality rate (P = 0.02), and increase of 130.6% in ICU utilization rate (P = 0.0001). There was no difference between the periods regarding mean number of inpatient days and reimbursed amounts. The indicators used in the present study showed improved effectiveness of acute ischemic stroke treatment with the use of a non-specific, decentralized protocol. However, no impact was observed on efficiency.

The Effects of Various Weather Conditions as a Potential Ischemic Stroke Trigger in Dogs

PubMed Central

Silver, Gena M.

2017-01-01

Stroke is the fifth leading cause of death in the United States, and is the leading cause of serious, long-term disability worldwide. There are at least 795,000 new or recurrent strokes each year, and approximately 85% of all stroke occurrences are ischemic. Unfortunately, companion animals are also at risk for ischemic stroke. Although the exact incidence of ischemic stroke in companion animals is unknown, some studies, and the veterinary information network (VIN), report that approximately 3% of neurological case referrals are due to a stroke. There is a long list of predisposing factors associated with the risk of ischemic stroke in both humans and canines; however, these factors do not explain why a stroke happens at a particular time on a particular day. Our understanding of these potential stroke “triggers” is limited, and the effect of transient environmental exposures may be one such “trigger”. The present study investigated the extent to which the natural occurrence of canine ischemic stroke was related to the weather conditions in the time-period immediately preceding the onset of stroke. The results of the present study demonstrated that the change in weather conditions could be a potential stroke trigger, with the strokes evaluated occurring after periods of rapid, large fluctuations in weather conditions. There are currently no epidemiological data on the seasonal variability of ischemic stroke in dogs, and determining whether canine stroke parallels human stroke would further validate the use of companion dogs as an appropriate naturally occurring model. PMID:29144407

The effect of a hydrogen sulfide releasing molecule (Na2S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model.

PubMed

Balaban, Cecilia Lucía; Rodríguez, Joaquín Valentín; Tiribelli, Claudio; Guibert, Edgardo Elvio

2015-08-01

Liver transplantation is currently the preferred treatment option for end-stage liver disease. Donation after cardiac death was a common practice in the early years of organ donation before brain death criteria were established. Those organs were subjected to variable periods of warm ischemia that might intensify cold ischemia/reperfusion injuries. In the present, shortage of brain dead donors has led to the reassessment of organ donation after cardiac death. Since many cytoprotective roles have been describe for H2S during ischemia/reperfusion on a variety of tissues, we hypothesized that graft exposure to this bioactive gas might improve preservation of non-heart beating donated organs. Therefore, to establish a rat model of donation post-cardiac arrest and using this approach to judge H2S delivery effects on graft hypothermic preservation, were the main objectives of this investigation. Cardiopulmonary arrest was induced in sedated rats by overload of potassium (K(+)). Livers were surgically removed and subsequently stored in HTK Solution (Histidine-tryptophan-ketoglutarate) at 0-4°C. After 24 h of hypothermic preservation, livers were rewarmed in an ex vivo model. Three experimental groups were established as follows: I--Livers procured before cardiac death and cold stored 24 h in HTK (BCD); II--Livers procured after cardiac death (45 min) and cold stored 24 h in HTK (ACD); III--Livers procured after cardiac death (45 min) and cold stored 24 h in HTK+10 μM Sodium Sulfide (Na2S) (ACD-SS). Data suggest that after 45 min of warm ischemia, viability parameters assessed during reperfusion in the ex vivo model were significantly impaired. Real time PCR revealed that after ex vivo reperfusion there is an increased expression of HO-1 and TNF-α and a modest drop in Bcl-2 mRNA, which could be interpreted as the cellular response to the hypoxic insult sustained during warm ischemia. On the other hand, warm ischemic livers exposed to H2S during cold storage, improved microcirculation, morphology and viability parameters during ex vivo reperfusion and showed significant modulation of HO-1 mRNA expression. In conclusion, HTK supplementation with Na2S arose as a potential treatment to recover non-heart beating harvested organs. Furthermore, an appropriate model of cardiac dead liver donors was successfully developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effects of traditional Chinese medicine formula NaoShuanTong capsule on haemorheology and cerebral energy metabolism disorders in rats with blood stasis.

PubMed

Liu, Hong; Peng, Yao-Yao; Liang, Feng-Yin; Chen, Si; Li, Pei-Bo; Peng, Wei; Liu, Zhong-Zheng; Xie, Cheng-Shi; Long, Chao-Feng; Su, Wei-Wei

2014-01-02

NaoShuanTong capsule (NSTC), an oral traditional Chinese medicine formula, is composed of Pollen Typhae , Radix Paeoniae Rubra , Rhizoma Gastrodiae , Radix Rhapontici and Radix Curcumae . It has been widely used to treat ischemic stroke in clinic for many years in China. In addition to neuronal apoptosis, haemorheology and cerebral energy metabolism disorders also play an important role in the pathogenesis and development of ischemic stroke. The present study was designed to evaluate the in vivo protective effects of NSTC on haemorheology and cerebral energy metabolism disorders in rats with blood stasis. Sixty specific pathogen-free sprague-dawley rats, male only, were randomly divided into six groups (control group, model group, aspirin (100 mg/kg/d) group, NSTC low-dose (400 mg/kg/d) group, NSTC intermediate-dose (800 mg/kg/d) group, NSTC high-dose (1600 mg/kg/d) group) with 10 animals in each. The rats except those in the control group were placed in ice-cold water (0-4 °C) for 5 min during the time interval (4 h) of two adrenaline hydrochloride injections (0.8 mg/kg) to induce blood stasis. After treatment, whole blood viscosity at three shear rates, plasma viscosity and erythrocyte sedimentation rate significantly decreased in NSTC intermediate- and high-dose groups; erythrocyte aggregation index and red corpuscle electrophoresis index significantly decreased in all the three dose NSTC groups. Moreover, treatment with high-dose NSTC could significantly improve Na + -K + adenosine triphosphatase (ATPase) and Ca 2+ ATPase activity, as well as lower lactic acid level in brain tissues. These results demonstrated the protective effects of NSTC on haemorheology and cerebral energy metabolism disorders, which may provide scientific information for the further understanding of mechanism(s) of NSTC as a clinical treatment for ischemic stroke. Furthermore, the protective effects of activating blood circulation as observed in this study might create valuable insight for the utilisation of NSTC to be a feasible alternative therapeutic agent for patients with blood stasis.

C-reactive protein gene C1444T polymorphism and risk of recurrent ischemic events in patients with symptomatic intracranial atherostenoses.

PubMed

Arenillas, Juan F; Massot, Andreu; Alvarez-Sabín, Jose; Fernandez-Cadenas, Israel; del Rio-Espinola, Albert; Chacon, Pilar; Quintana, Manuel; Molina, Carlos A; Rovira, Alex; Montaner, Joan

2009-01-01

High levels of C-reactive protein (CRP) are associated with an increased risk of further ischemic events in patients with symptomatic intracranial atherosclerotic disease (ICAD). It remains unknown to which extent this increased risk might be genetically predetermined. We aimed to investigate the relationship between a common genetic polymorphism of the CRP gene and the risk of recurrent ischemic events in symptomatic ICAD patients. We studied 75 consecutive patients with a first-ever cerebral ischemic event attributable to symptomatic ICAD. Blood samples were drawn 3 months after the qualifying event. Genomic DNA was isolated and the C1444T single nucleotide polymorphism (SNP) of the CRP gene was determined. The blood concentration of CRP was also measured. Patients underwent long-term clinical follow-up to detect the occurrence of further major ischemic events. During a median follow-up time of 23 months, 18 patients (24%) suffered a major ischemic event (10 ischemic strokes, 3 transient ischemic attacks and 5 myocardial infarctions). Raised CRP levels at baseline (p = 0.02) and the presence of the T allele within the CRP C1444T SNP were associated with a higher risk of recurrent ischemic events (p = 0.02). Kaplan-Meier and multivariable Cox regression analyses adjusted for age, sex, vascular risk factors and CRP level identified that the presence of the T allele in the studied polymorphism predicted the occurrence of further ischemic events (hazard ratio 3.6, 95% confidence interval 1.2-11.1; p = 0.025). The presence of the T allele within the CRP gene C1444T polymorphism may be associated with a higher risk of further ischemic events in symptomatic ICAD patients. (c) 2009 S. Karger AG, Basel.

[Prevention of perioperative hypothermia].

PubMed

Horn, Ernst-Peter; Torossian, Alexander

2010-03-01

Inadvertent perioperative hypothermia impairs postoperative outcome in surgical patients due to ischemic myocardial events, wound infections and coagulation disorders. Body core temperature should be assessed 1-2h preoperatively and continuously during surgery. To prevent hypothermia patients and nursing clinical staff should be teached and trained. Preoperatively surgical patients should always be prewarmed by using convective warming devices and active warming should be continued in surgeries longer than 1 hour. Warming of IV fluids is effective if infusion rates are above 1l/h. Core temperature should be measured in the recovery room and active warming should be started when patients are hypothermic or if they feel cold. Georg Thieme Verlag Stuttgart * New York.

Relationship of initial hematocrit level to discharge destination and resource utilization after ischemic stroke: a pilot study.

PubMed

Diamond, Paul T; Gale, Shawn D; Evans, Brent A

2003-07-01

To examine the association between initial hematocrit level at the time of ischemic stroke, discharge destination, and resource utilization. Case series. University hospital. A total of 1012 consecutive patients with ischemic stroke admitted to a university health system between August 3, 1995, and June 24, 1999. Not applicable. Length of stay, hospital cost, and discharge disposition. Of 1012 patients presenting with ischemic stroke, 58% were discharged home, 10% were discharged home with home care services, 15% were discharged to a rehabilitation hospital, 11% were discharged to a skilled or intermediate care facility, and 6% died. After adjusting for age, sex, race, and comorbidities, a significant association (P=.009) existed between discharge outcome and initial hematocrit level. The probability of achieving an equivalent or less favorable outcome increased at both high and low hematocrit levels, with a minimum probability at a hematocrit level of approximately 45%. An association exists between hematocrit level at the time of ischemic stroke and discharge outcome. Midrange hematocrit levels appear to be associated with discharge to home rather than to an inpatient rehabilitation unit or to a nursing facility. Further study is indicated to examine the relationship among hematocrit level, stroke severity, and outcome.

[Silent myocardial ischemia and exercise-induced arrhythmia detected by the exercise test in the total health promotion plan (THP)].

PubMed

Iwane, M; Shibe, Y; Itoh, K; Kinoshita, F; Kanagawa, Y; Kobayashi, M; Mugitani, K; Ohta, M; Ohata, H; Yoshikawa, A; Ikuta, Z; Nakamura, Y; Mohara, O

2001-03-01

We investigated the prevalence and characteristics of ischemic heart disease especially silent myocardial ischemia (SMI) and arrhythmia in need of careful observation in the exercise stress tests in the Total Health Promotion Plan (THP), which was conducted between 1994-96 for the purpose of measuring cardiopulmonary function. All workers (n = 4,918, 4,426 males) aged 18-60 yr old in an occupational field were studied. Exercise tests with an ergometer were performed by the LOPS protocol, in which the maximal workload was set up as a presumed 70-80% maximal oxygen intake, or STEP (original multistage protocol). ECG changes were evaluated with a CC5 lead. Two hundred and fifteen people refused the study because of a common cold, lumbago and so on. Of 4,703 subjects, 17 with abnormal rest ECG and 19 with probable anginal pain were excluded from the exercise tests. Of 4,667 who underwent the exercise test, 37 (0.79%) had ischemic ECG change, and 155 (3.32%) had striking arrhythmia. These 228 subjects then did a treadmill exercise test with Bruce protocol. Twenty-two (0.47% of 4,703) showed positive ECG change, 9 (0.19%) of 22 had abnormal findings on a 201Tl scan. 8 (0.17%) were diagnosed as SMI (Cohn I), in which the prevalence of hypertension, hyperlipidemia, diabetes mellitus, smoker and positive familial history of ischemic heart disease was greater than that of all subjects. In a 15-30 month follow up, none has developed cardiac accidents. Exercise-induced arrhythmia was detected in 11 (0.23%) subjects. Four were non-sustained ventricular tachycardia without any organic disease, 4 were ventricular arrhythmia based on cardiomyopathy detected by echocardiography, 2 were atrial fibrillation and another was WPW syndrome. It is therefore likely that the ergometer exercise test in THP was effective in preventing sudden death caused by ischemic heart disease or striking arrhythmia.

ABCD3-I score and the risk of early or 3-month stroke recurrence in tissue- and time-based definitions of TIA and minor stroke.

PubMed

Mayer, Lukas; Ferrari, Julia; Krebs, Stefan; Boehme, Christian; Toell, Thomas; Matosevic, Benjamin; Tinchon, Alexander; Brainin, Michael; Gattringer, Thomas; Sommer, Peter; Thun, Peter; Willeit, Johann; Lang, Wilfried; Kiechl, Stefan; Knoflach, Michael

2018-03-01

Changing definition of TIA from time to a tissue basis questions the validity of the well-established ABCD3-I risk score for recurrent ischemic cerebrovascular events. We analyzed patients with ischemic stroke with mild neurological symptoms arriving < 24 h after symptom onset in a phase where it is unclear, if the event turns out to be a TIA or minor stroke, in the prospective multi-center Austrian Stroke Unit Registry. Patients were retrospectively categorized according to a time-based (symptom duration below/above 24 h) and tissue-based (without/with corresponding brain lesion on CT or MRI) definition of TIA or minor stroke. Outcome parameters were early stroke during stroke unit stay and 3-month ischemic stroke. Of the 5237 TIA and minor stroke patients with prospectively documented ABCD3-I score, 2755 (52.6%) had a TIA by the time-based and 2183 (41.7%) by the tissue-based definition. Of the 2457 (46.9%) patients with complete 3-month followup, corresponding numbers were 1195 (48.3%) for the time- and 971 (39.5%) for the tissue-based definition of TIA. Early and 3-month ischemic stroke occurred in 1.1 and 2.5% of time-based TIA, 3.8 and 5.9% of time-based minor stroke, 1.2 and 2.3% of tissue-based TIA as well as in 3.1 and 5.5% of tissue-based minor stroke patients. Irrespective of the definition of TIA and minor stroke, the risk of early and 3-month ischemic stroke steadily increased with increasing ABCD3-I score points. The ABCD3-I score performs equally in TIA patients in tissue- as well as time-based definition and the same is true for minor stroke patients.

[Effect of Chinese drugs for activating blood circulation and removing blood stasis on carotid atherosclerosis and ischemic cerebrovascular events].

PubMed

Lu, Yan; Li, Tao

2014-03-01

To explore the effect of Chinese drugs for activating blood circulation and removing blood stasis (CDABCRBS) on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events. By using open and control method, effect of 4 groups of platelet antagonists, platelet antagonists + CDABCRBS, platelet antagonists +atorvastatin, platelet antagonists +atorvastatin +CDABCRBS on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events of 90 cerebral infarction patients were analyzed. Through survival analysis, there was no statistical difference in the effect of the 4 interventions on the variation of carotid stenosis rates or ischemic cerebrovascular events (P > 0.05). The occurrence of ischemic cerebrovascular events could be postponed by about 4 months in those treated with platelet antagonists + CDABCRBS and platelet antagonists + atorvastatin +CDABCRBS. By multivariate Logistic analysis, age, hypertension, and clopidogrel were associated with stenosis of extracranial carotid arteries (P <0.05). Age, diabetes, aspirin, clopidogrel, CDABCRBS were correlated with cerebrovascular accidents (P < 0.05). Whether or not accompanied with hypertension is an influential factor for carotid stenosis, but it does not affect the occurrence of ischemic cerebrovascular events. CDABCRBS could effectively prolong the occurrence time of ischemic cerebrovascular events.

Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study.

PubMed

Banerjee, Chirantan; Moon, Yeseon P; Paik, Myunghee C; Rundek, Tatjana; Mora-McLaughlin, Consuelo; Vieira, Julio R; Sacco, Ralph L; Elkind, Mitchell S V

2012-05-01

Diabetes increases stroke risk, but whether diabetes status immediately before stroke improves prediction and whether duration is important are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. Among 3298 stroke-free participants in the Northern Manhattan Study, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median, 9 years). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors. Mean age was 69 ± 10 years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and 10% had development of diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR, 2.5; 95% CI, 1.9-3.3) and diabetes considered as a time-dependent covariate (HR, 2.4; 95% CI, 1.8-3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR, 1.03 per year with diabetes; 95% CI, 1.02-1.04). Compared to nondiabetic participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1-2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1-3.0), and ≥ 10 years (adjusted HR, 3.2; 95% CI, 2.4-4.5) were at increased risk. Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥ 10 years.

[Primary emergencies: management of acute ischemic stroke].

PubMed

Leys, Didier; Goldstein, Patrick

2012-01-01

The emergency diagnostic strategy for acute ischemic stroke consists of:--identification of stroke, based on clinical examination (sudden onset of a focal neurological deficit);--identification of the ischemic or hemorrhagic nature by MRI or CT;--determination of the early time-course (clinical examination) and the cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same general management (treatment of a life-threatening emergency, ensuring normal biological parameters except for blood pressure, and prevention of complications);--decompressive surgery in the rare cases of intracranial hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for patients admitted with 4.5 hours of stroke onset who have no contraindications, and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These treatments should be administered within a few hours. A centralized emergency call system (phone number 15 in France) is the most effective way of achieving this objective.

Risk factors, mortality, and timing of ischemic and hemorrhagic stroke with left ventricular assist devices.

PubMed

Frontera, Jennifer A; Starling, Randall; Cho, Sung-Min; Nowacki, Amy S; Uchino, Ken; Hussain, M Shazam; Mountis, Maria; Moazami, Nader

2017-06-01

Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death—A Dutch Cohort Study

PubMed Central

Peters-Sengers, Hessel; Homan van der Heide, Jaap J.; Heemskerk, Martin B. A.; ten Berge, Ineke J. M.; Ultee, Fred C. W.; Idu, Mirza M.; Betjes, Michiel G. H.; van Zuilen, Arjan D.; Christiaans, Maarten H. L.; Hilbrands, Luuk H.; de Vries, Aiko P. J.; Nurmohamed, Azam S.; Berger, Stefan P.; Bemelman, Frederike J.

2017-01-01

Background Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. Methods We used the Dutch Organ Transplantation Registry to include recipients (≥18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). Results Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m2 and cDCD, 45.8 (24.1) mL/min/m2; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m2 and cDCD, 47.7 (21.7) mL/min/m2; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. Conclusions We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction. PMID:27257998

Evaluation of asymmetries of blood flow rate and of circulation time by intravenous radionuclide cerebral angiography in patients with ischemic completed stroke.

PubMed

Bartolini, A; Primavera, A; Gasparetto, B

1984-12-01

155 patients with ischemic completed stroke of varying severity and outcome have been evaluated by radionuclide cerebral angiography with analysis of regional time-activity curves. Two parameters have been evaluated: area under the upslope of the curve (Aup) reflecting regional blood flow rate and moment of the whole curve reflecting tracer circulation time (rABCT) Combination of these two methods ensured increased detection of perfusion asymmetries.

Hemorrhagic versus ischemic stroke: Who can best benefit from blended conventional physiotherapy with robotic-assisted gait therapy?

PubMed

Dierick, Frédéric; Dehas, Mélanie; Isambert, Jean-Luc; Injeyan, Soizic; Bouché, Anne-France; Bleyenheuft, Yannick; Portnoy, Sigal

2017-01-01

Contrary to common belief of clinicians that hemorrhagic stroke survivors have better functional prognoses than ischemic, recent studies show that ischemic survivors could experience similar or even better functional improvements. However, the influence of stroke subtype on gait and posture outcomes following an intervention blending conventional physiotherapy with robotic-assisted gait therapy is missing. This study compared gait and posture outcome measures between ambulatory hemorrhagic patients and ischemic patients, who received a similar 4 weeks' intervention blending a conventional bottom-up physiotherapy approach and an exoskeleton top-down robotic-assisted gait training (RAGT) approach with Lokomat. Forty adult hemiparetic stroke inpatient subjects were recruited: 20 hemorrhagic and 20 ischemic, matched by age, gender, side of hemisphere lesion, stroke severity, and locomotor impairments. Functional Ambulation Category, Postural Assessment Scale for Stroke, Tinetti Performance Oriented Mobility Assessment, 6 Minutes Walk Test, Timed Up and Go and 10-Meter Walk Test were performed before and after a 4-week long intervention. Functional gains were calculated for all tests. Hemorrhagic and ischemic subjects showed significant improvements in Functional Ambulation Category (P<0.001 and P = 0.008, respectively), Postural Assessment Scale for Stroke (P<0.001 and P = 0.003), 6 Minutes Walk Test (P = 0.003 and P = 0.015) and 10-Meter Walk Test (P = 0.001 and P = 0.024). Ischemic patients also showed significant improvements in Timed Up and Go. Significantly greater mean Functional Ambulation Category and Tinetti Performance Oriented Mobility Assessment gains were observed for hemorrhagic compared to ischemic, with large (dz = 0.81) and medium (dz = 0.66) effect sizes, respectively. Overall, both groups exhibited quasi similar functional improvements and benefits from the same type, length and frequency of blended conventional physiotherapy and RAGT protocol. The use of intensive treatment plans blending top-down physiotherapy and bottom-up robotic approaches is promising for post-stroke rehabilitation.

Hemorrhagic versus ischemic stroke: Who can best benefit from blended conventional physiotherapy with robotic-assisted gait therapy?

PubMed Central

Dehas, Mélanie; Isambert, Jean-Luc; Injeyan, Soizic; Bouché, Anne-France; Bleyenheuft, Yannick; Portnoy, Sigal

2017-01-01

Background Contrary to common belief of clinicians that hemorrhagic stroke survivors have better functional prognoses than ischemic, recent studies show that ischemic survivors could experience similar or even better functional improvements. However, the influence of stroke subtype on gait and posture outcomes following an intervention blending conventional physiotherapy with robotic-assisted gait therapy is missing. Objective This study compared gait and posture outcome measures between ambulatory hemorrhagic patients and ischemic patients, who received a similar 4 weeks’ intervention blending a conventional bottom-up physiotherapy approach and an exoskeleton top-down robotic-assisted gait training (RAGT) approach with Lokomat. Methods Forty adult hemiparetic stroke inpatient subjects were recruited: 20 hemorrhagic and 20 ischemic, matched by age, gender, side of hemisphere lesion, stroke severity, and locomotor impairments. Functional Ambulation Category, Postural Assessment Scale for Stroke, Tinetti Performance Oriented Mobility Assessment, 6 Minutes Walk Test, Timed Up and Go and 10-Meter Walk Test were performed before and after a 4-week long intervention. Functional gains were calculated for all tests. Results Hemorrhagic and ischemic subjects showed significant improvements in Functional Ambulation Category (P<0.001 and P = 0.008, respectively), Postural Assessment Scale for Stroke (P<0.001 and P = 0.003), 6 Minutes Walk Test (P = 0.003 and P = 0.015) and 10-Meter Walk Test (P = 0.001 and P = 0.024). Ischemic patients also showed significant improvements in Timed Up and Go. Significantly greater mean Functional Ambulation Category and Tinetti Performance Oriented Mobility Assessment gains were observed for hemorrhagic compared to ischemic, with large (dz = 0.81) and medium (dz = 0.66) effect sizes, respectively. Conclusion Overall, both groups exhibited quasi similar functional improvements and benefits from the same type, length and frequency of blended conventional physiotherapy and RAGT protocol. The use of intensive treatment plans blending top-down physiotherapy and bottom-up robotic approaches is promising for post-stroke rehabilitation. PMID:28575054

Heart rate and ischemic stroke: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

O'Neal, Wesley T; Qureshi, Waqas T; Judd, Suzanne E; Meschia, James F; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2015-12-01

The association between resting heart rate and ischemic stroke remains unclear. To examine the association between resting heart rate and ischemic stroke. A total of 24 730 participants (mean age: 64 ± 9·3 years; 59% women; 41% blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment (2003-2007) were included in this analysis. Resting heart rate was determined from baseline electrocardiogram data. Heart rate was examined as a continuous variable per 10 bpm increase and also as a categorical variable using tertiles ( <61 bpm, 61 to 70 bpm, and >70 bpm). First-time ischemic stroke events were identified during follow-up and adjudicated by physician review. Over a median follow-up of 7·6 years, a total of 646 ischemic strokes occurred. In a Cox regression model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, each 10 bpm increase in heart rate was associated with a 10% increase in the risk of ischemic stroke (hazard ratio = 1·10, 95% confidence interval = 1·02, 1·18). In the categorical model, an increased risk of ischemic stroke was observed for heart rates in the middle (hazard ratio = 1·29, 95% confidence interval = 1·06, 1·57) and upper (hazard ratio = 1·37, 95% confidence interval = 1·12, 1·67) tertiles compared with the lower tertile. The results were consistent when the analysis was stratified by age, gender, race, exercise habits, hypertension, and coronary heart disease. In REGARDS, high resting heart rates were associated with an increased risk of ischemic stroke compared with low heart rates. Further research is needed to examine whether interventions aimed to reduce heart rate decrease stroke risk. © 2015 World Stroke Organization.

Direct stimulation of angiotensin II type 2 receptor initiated after stroke ameliorates ischemic brain damage.

PubMed

Min, Li-Juan; Mogi, Masaki; Tsukuda, Kana; Jing, Fei; Ohshima, Kousei; Nakaoka, Hirotomo; Kan-No, Harumi; Wang, Xiao-Li; Chisaka, Toshiyuki; Bai, Hui-Yu; Iwanami, Jun; Horiuchi, Masatsugu

2014-08-01

Stroke is a leading cause of death and disability; however, meta-analysis of randomized controlled trials of blood pressure-lowering drugs in acute stroke has shown no definite evidence of a beneficial effect on functional outcome. Accumulating evidence suggests that angiotensin II type 1 receptor blockade with angiotensin II type 2 (AT2) receptor stimulation could contribute to protection against ischemic brain damage. We examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) initiated even after stroke can prevent ischemic brain damage. Stroke was induced by middle cerebral artery (MCA) occlusion, and the area of cerebral infarction was measured by magnetic resonant imaging. C21 (10 µg/kg/day) treatment was initiated immediately after MCA occlusion by intraperitoneal injection followed by treatment with C21 once daily. We observed that ischemic area was enlarged in a time dependent fashion and decreased on day 5 after MCA occlusion. Treatment with C21 initiated after MCA occlusion significantly reduced the ischemic area, with improvement of neurological deficit in a time-dependent manner without affecting blood pressure. The decrease of cerebral blood flow after MCA occlusion was also ameliorated by C21 treatment. Moreover, treatment with C21 significantly attenuated superoxide anion production and expression of proinflammatory cytokines, monocyte chemoattractant protein 1, and tumor necrosis factor α. Interestingly, C21 administration significantly decreased blood-brain barrier permeability and cerebral edema on the ischemic side. These results provide new evidence that direct AT2 receptor stimulation with C21 is a novel therapeutic approach to prevent ischemic brain damage after acute stroke. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties

PubMed Central

Cerasuolo, Joshua O.; Cipriano, Lauren E.; Sposato, Luciano A.

2017-01-01

Purpose of review Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research. Recent findings Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated. Summary AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants. PMID:27984303

Trends in ischemic heart disease mortality in Korea, 1985-2009: an age-period-cohort analysis.

PubMed

Lee, Hye Ah; Park, Hyesook

2012-09-01

Economic growth and development of medical technology help to improve the average life expectancy, but the western diet and rapid conversions to poor lifestyles lead an increasing risk of major chronic diseases. Coronary heart disease mortality in Korea has been on the increase, while showing a steady decline in the other industrialized countries. An age-period-cohort analysis can help understand the trends in mortality and predict the near future. We analyzed the time trends of ischemic heart disease mortality, which is on the increase, from 1985 to 2009 using an age-period-cohort model to characterize the effects of ischemic heart disease on changes in the mortality rate over time. All three effects on total ischemic heart disease mortality were statistically significant. Regarding the period effect, the mortality rate was decreased slightly in 2000 to 2004, after it had continuously increased since the late 1980s that trend was similar in both sexes. The expected age effect was noticeable, starting from the mid-60's. In addition, the age effect in women was more remarkable than that in men. Women born from the early 1900s to 1925 observed an increase in ischemic heart mortality. That cohort effect showed significance only in women. The future cohort effect might have a lasting impact on the risk of ischemic heart disease in women with the increasing elderly population, and a national prevention policy is need to establish management of high risk by considering the age-period-cohort effect.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.

PubMed

Moeser, Adam-J; Nighot, Prashant-K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony-T

2008-10-21

To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin. This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

PubMed Central

Moeser, Adam J; Nighot, Prashant K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony T

2008-01-01

AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer’s solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1 μmol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of 3H-mannitol and 14C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier. PMID:18932279

Renal histopathology features according to various warm ischemia times in porcine laparoscopic and open surgery model

PubMed Central

Sabbagh, Robert; Chawla, Arun; Tisdale, Britton; Kwan, Kevin; Chatterjee, Suman; Kwiecien, Jacek M.; Kapoor, Anil

2011-01-01

Background Thirty minutes has been considered as the threshold for tolerable warm ischemic time (WIT). Recent reports demonstrate recovery of renal function after longer WIT. We assessed renal histology according to different WIT in a 2-kidney porcine model. Methods Twelve female pigs were randomized to an open or laparoscopic group. Each pig was further randomized within each group to clamping the left renal artery for 5, 15, 30, 45, 60 or 180 minutes. Preclamping left renal biopsies were performed on each pig. The contralateral kidney in each animal was used as an individual control. On postoperative day 14, all animals underwent bilateral nephrectomies. Preclamping left renal biopsies and all renal specimens were evaluated by a blinded veterinary pathologist. Results One pig died in the open group after 180 minutes of clamping. Histopathology did not show any significant changes between the two groups and across clamp times from 5 to 60 minutes. After 180 minutes of laparoscopic clamping, there was evidence of diffuse necrosis. Interpretation Sixty minutes of ischemia did not show any permanent renal damage in both groups. Further studies are needed to verify these findings in humans. A prolonged ischemic time without permanent renal damage would be helpful in partial nephrectomy. Warm ischemic time of 180 minutes exceeded the renal ischemic burden based on histological features. PMID:21470513

Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target.

PubMed

Gurbel, Paul A; Antonino, Mark J; Bliden, Kevin P; Dichiara, Joseph; Suarez, Thomas A; Singla, Anand; Tantry, Udaya S

2008-12-01

Platelets play a central role in the genesis of post-percutaneous coronary intervention (PCI) ischemic events. High post-procedural platelet reactivity to adenosine diphosphate (HPR(ADP)) may be a risk factor for ischemic events after PCI. The study was designed to evaluate a cutpoint of platelet reactivity that is associated with the occurrence of ischemic events after PCI. Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 297 consecutive patients undergoing non-emergent PCI. Patients were prospectively followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Eighty-one patients (27%) suffered ischemic events. Patients with ischemic events had higher 5 microM ADP-induced platelet aggregation (46 +/- 14% vs. 30 +/- 17%, p < 0.001) and 20 microM ADP-induced platelet aggregation (60 +/- 13% vs. 43 +/- 19%, p < 0.001) compared to patients without ischemic events. Using a combined receiver operator curve analysis, cutpoints of >46% aggregation following 5 microM ADP stimulation and >59% aggregation following 20 microM ADP stimulation (HPR(ADP)) were associated with 58 and 54% of ischemic events, respectively. Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPR(ADP) cutpoints (5 microM ADP, OR=3.9, and 20 microM ADP, OR=3.8, p < 0.001 for both). High post-procedural platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data support a potential therapeutic target for antiplatelet therapy based on the results of an ex vivo platelet function test. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

PubMed

Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

2017-04-01

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Critical Ischemia Times and the Effect of Novel Preservation Solutions HTK-N and TiProtec on Tissues of a Vascularized Tissue Isograft.

PubMed

Messner, Franka; Hautz, Theresa; Blumer, Michael J F; Bitsche, Mario; Pechriggl, Elisabeth J; Hermann, Martin; Zelger, Bettina; Zelger, Bernhard; Öfner, Dietmar; Schneeberger, Stefan

2017-09-01

We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.

Accepting multiple simultaneous liver offers does not negatively impact transplant outcomes.

PubMed

Eldeen, Firas Zahr; Mourad, Moustafa Mabrouk; Bhandari, Mayank; Roll, Garrett; Gunson, Bridget; Mergental, Hynek; Bramhall, Simon; Isaac, John; Muiesan, Paolo; Mirza, Darius F; Perera, M Thamara P R

2016-02-01

Impact of performing multiple liver transplants (LT) in a short period of time is unknown. Consecutively performed LT potentially increase complication rates through team fatigue and overutilization of resources and increase ischemia time. We analyzed the impact of undertaking consecutive LT (Consecutive liver transplant, CLT; LT preceded by another transplant performed not more than 12 h before, both transplants grouped together) on outcomes. Of 1702 LT performed, 314 (18.4%) were CLT. Outcome data was compared with solitary LT (SLT; not more than one LT in 12-h period). Recipient, donor, and graft characteristics were evenly matched between SLT and CLT; second LT of CLT group utilized younger donors grafts with longer cold ischemic times (P = 0.015). Implantation and operative time were significantly lower in CLT recipients on intergroup analysis (P = 0.0001 and 0.002, respectively). Early hepatic artery thrombosis (E-HAT) was higher in CLT versus SLT (P = 0.038), despite absolute number of E-HAT being low in all groups. Intragroup analysis demonstrated a trend toward more frequent E-HAT in first LT, compared to subsequent transplants; however, difference did not reach statistical significance (P = 0.135). In era of organ scarcity, CLT performed at high-volume center is safe and allows pragmatic utilization of organs, potentially reducing number of discarded grafts and reducing waiting list mortality. © 2015 Steunstichting ESOT.

Effects of Postconditioning on Skeletal Muscle Injury and Apoptosis Induced by Partial Ischemia and Reperfusion in Rats.

PubMed

Lintz, José Alves; Dalio, Marcelo Bellini; Tirapelli, Luiz Fernando; Ribeiro, Maurício Serra; Joviliano, Edwaldo Edner; Piccinato, Carlos Eli

2017-04-01

Analyze the effects of ischemic postconditioning on skeletal muscle injury and apoptosis produced by partial ischemia and reperfusion in rats. An experimental study was designed using 70 Wistar rats divided in 3 groups: Sham; Control-submitted to ischemia and reperfusion; and Postconditioning-submitted to ischemia and reperfusion with ischemic postconditioning. Subgroups (n = 10) were divided by duration of ischemia (4, 5, or 6 hr). A partial ischemia model using aortic clamping was used. The postconditioning protocol consisted of 3 cycles of clamping the aorta for 1 min and releasing for another minute. Skeletal muscle injury was evaluated by measuring serum levels of releasing cytoplasmic enzymes: aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and total creatine phosphokinase (CPK). Lipid peroxidation was evaluated by muscular levels of malondialdehyde (MDA). Energetic cell storage was evaluated by muscular glycogen levels. Apoptosis was evaluated analyzing the expression of caspase 3 and protein B-cell lymphoma 2 (Bcl-2) by immunohistochemistry. AST levels in Sham group were 109.80 units/L, in Control subgroups were 4h 200.60 units/L/5h 392.30 units/L/6h 118.82 units/L, whereas in Postconditioning subgroups were: 4h 316.10 units/L/5h 268.40 units/L/6h 267.00 units/L. There was a 2-3-fold increase in Control and Postconditioning groups compared with Sham group (P = 0.003) There was no difference between groups with the same ischemic injury time. LDH, CPK, and MDA levels were similar in Sham, Control, and Postconditioning groups. Subgroups with the same ischemic injury time were also similar. Glycogen levels in Sham group were 0.629 mg%, in Control subgroups were 4h 0.323 mg%/5h 0.348 mg%/6h 0.183 mg%, whereas in Postconditioning subgroups were: 4h 0.443 mg%/5h 0.270 mg%/6h 0.324 mg%. Control and Postconditioning groups were decreased by half in relation with the Sham group (P = 0.002), with no difference between groups with the same ischemic injury time. For both caspase 3 and Bcl-2, the percentage of positive cells increased more than 2-fold in Control and Postconditioning groups when compared with Sham group (P < 0.001). The greater the ischemic injury time, the greater was the percent of positive cells (P < 0.0005), with no difference between subgroups with the same ischemic injury time. Ischemic postconditioning had neither protective effect on skeletal muscle injury nor avoided apoptosis induction in rats submitted to partial ischemia and reperfusion. Copyright © 2017 Elsevier Inc. All rights reserved.

Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe3 O4 Nanoparticle-based MR Imaging Probe.

PubMed

Wang, Ting; Hou, Yi; Bu, Bo; Wang, Wenxin; Ma, Tiancong; Liu, Chunyan; Lin, Lan; Ma, Lin; Lou, Xin; Gao, Mingyuan

2018-04-17

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α v β 3 -specific Fe 3 O 4 -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe 3 O 4 -RGD nanoprobe and the Fe 3 O 4 mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe 3 O 4 -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Feasibility of acute thrombolytic therapy for stroke.

PubMed

Nandigam, K; Narayan, S K; Elangovan, S; Dutta, T K; Sethuraman, K R; Das, A K

2003-12-01

Thrombolysis is an expensive medical intervention for ischemic stroke and hence there is a need to study the feasibility of thrombolysis in rural India. To asses the feasibility and limitations of providing thrombolytic therapy to acute ischemic stroke patients in a rural Indian set-up. The first 64 consecutive patients registered under the Acute Stroke Registry in a university referral hospital with a rural catchment area were studied as per a detailed protocol and questionnaire. Of the 64 patients 44 were ischemic strokes, and 20 were hemorrhagic. Thirteen (29.55%) patients with ischemic stroke reached a center with CT scan facility within 3 hours, of whom only 7 (15.91%) were eligible to receive thrombolytic therapy as per the existing clinical and radiological criteria, but none received the therapy. Of the remaining 31 (70.45%) who arrived late, 11 (25%) had no clinical and radiological contraindications for thrombolysis, except the time factor. All the patients belonged to a low socioeconomic status and a rural background. Though a large proportion of ischemic stroke patients were eligible to receive thrombolytic therapy, the majority could not reach a center with adequate facilities within the recommended time window. More alarmingly, even for those patients who reached within the time window, no significant attempt was made to initiate thrombolysis. These data call not only for attention to improve existing patient transport facilities, but also for improving the awareness of efficacy and therapeutic window of thrombolysis in stroke, among the public as well as primary care doctors.

Impact of Ischemic and Valvular Heart Disease on Atrial Excitation:A High-Resolution Epicardial Mapping Study.

PubMed

Mouws, Elisabeth M J P; Lanters, Eva A H; Teuwen, Christophe P; van der Does, Lisette J M E; Kik, Charles; Knops, Paul; Yaksh, Ameeta; Bekkers, Jos A; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-08

The influence of underlying heart disease or presence of atrial fibrillation (AF) on atrial excitation during sinus rhythm (SR) is unknown. We investigated atrial activation patterns and total activation times of the entire atrial epicardial surface during SR in patients with ischemic and/or valvular heart disease with or without AF. Intraoperative epicardial mapping (N=128/192 electrodes, interelectrode distances: 2 mm) of the right atrium, Bachmann's bundle (BB), left atrioventricular groove, and pulmonary vein area was performed during SR in 253 patients (186 male [74%], age 66±11 years) with ischemic heart disease (N=132, 52%) or ischemic valvular heart disease (N=121, 48%). As expected, SR origin was located at the superior intercaval region of the right atrium in 232 patients (92%). BB activation occurred via 1 wavefront from right-to-left (N=163, 64%), from the central part (N=18, 7%), or via multiple wavefronts (N=72, 28%). Left atrioventricular groove activation occurred via (1) BB: N=108, 43%; (2) pulmonary vein area: N=9, 3%; or (3) BB and pulmonary vein area: N=136, 54%; depending on which route had the shortest interatrial conduction time ( P <0.001). Ischemic valvular heart disease patients more often had central BB activation and left atrioventricular groove activation via pulmonary vein area compared with ischemic heart disease patients (N=16 [13%] versus N=2 [2%]; P =0.009 and N=86 [71%] versus N=59 [45%]; P <0.001, respectively). Total activation times were longer in patients with AF (AF: 136±20 [92-186] ms; no AF: 114±17 [74-156] ms; P <0.001), because of prolongation of right atrium ( P =0.018) and BB conduction times ( P <0.001). Atrial excitation during SR is affected by underlying heart disease and AF, resulting in alternative routes for BB and left atrioventricular groove activation and prolongation of total activation times. Knowledge of atrial excitation patterns during SR and its electropathological variations, as demonstrated in this study, is essential to further unravel the pathogenesis of AF. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation.

PubMed

Compagnon, Philippe; Levesque, Eric; Hentati, Hassen; Disabato, Mara; Calderaro, Julien; Feray, Cyrille; Corlu, Anne; Cohen, José Laurent; Ben Mosbah, Ismail; Azoulay, Daniel

2017-07-01

Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.

[Modern technologies and prospects of rehabilitation of patients after ischemic stroke].

PubMed

Ekusheva, E V

Despite the great achievements in the field of neurorehabilitation, a significant proportion of patients after an ischemic stroke have persistent motor disturbances even after timely and adequately carried out restorative measures. The article discusses the issues of neuroplasticity, modern diagnostic technologies for studying this phenomenon; prognostic factors for recovery deficit following stroke and determining the effectiveness of ongoing treatment. The principles of neuroprotective therapy in ischemic stroke are considered, which is a pathogenetically justified direction at all stages of restorative treatment after cerebral circulation disorders. One of the most studied original cytoprotectors, demonstrating safety, efficacy and good tolerability, is cytoflavin. The results of numerous clinical trials have revealed a significant positive clinical and morphological dynamics when taking cytoflavin in patients after ischemic stroke.

Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy).

PubMed

Puy, Laurent; De Guio, François; Godin, Ophélia; Duering, Marco; Dichgans, Martin; Chabriat, Hugues; Jouvent, Eric

2017-10-01

Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P =0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data. © 2017 American Heart Association, Inc.

Non-Invasive Monitoring of CNS MHC-I Molecules in Ischemic Stroke Mice.

PubMed

Xia, Jing; Zhang, Ying; Zhao, Huanhuan; Wang, Jie; Gao, Xueren; Chen, Jinpeng; Fu, Bo; Shen, Yuqing; Miao, Fengqin; Zhang, Jianqiong; Teng, Gaojun

2017-01-01

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. The expression of major histocompatibility complex class I (MHC-I) molecules in the central nervous system, which are silenced under normal physiological conditions, have been reported to be induced by injury stimulation. The purpose of this study was to determine whether MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke and to assess whether a high-affinity peptide specific for MHC-I molecules could be applied in the near-infrared imaging of cerebral ischemic mice. Quantitative real-time PCR and Western blotting were used to detect the expression of MHC-I molecules in two mouse models of cerebral ischemic stroke and an in vitro model of ischemia. The NetMHC 4.0 server was used to screen a high-affinity peptide specific for mouse MHC-I molecules. The Rosetta program was used to identify the specificity and affinity of the screened peptide (histocompatibility-2 binding peptide, H2BP). The results demonstrated that MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke. Cy5.5-H2BP molecular probes could be applied in the near-infrared imaging of cerebral ischemic mice. Research on the expression of MHC-I molecules in the acute phase after ischemia and MHC-I-targeted imaging may not only be helpful for understanding the mechanism of ischemic and hypoxic brain injury and repair but also has potential application value in the imaging of ischemic stroke.

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

PubMed

Kilarski, Laura L; Achterberg, Sefanja; Devan, William J; Traylor, Matthew; Malik, Rainer; Lindgren, Arne; Pare, Guillame; Sharma, Pankaj; Slowik, Agniesczka; Thijs, Vincent; Walters, Matthew; Worrall, Bradford B; Sale, Michele M; Algra, Ale; Kappelle, L Jaap; Wijmenga, Cisca; Norrving, Bo; Sandling, Johanna K; Rönnblom, Lars; Goris, An; Franke, Andre; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Holliday, Elizabeth G; Fornage, Myriam; Psaty, Bruce; Gretarsdottir, Solveig; Thorsteinsdottir, Unnar; Seshadri, Sudha; Mitchell, Braxton D; Kittner, Steven; Clarke, Robert; Hopewell, Jemma C; Bis, Joshua C; Boncoraglio, Giorgio B; Meschia, James; Ikram, M Arfan; Hansen, Bjorn M; Montaner, Joan; Thorleifsson, Gudmar; Stefanson, Kari; Rosand, Jonathan; de Bakker, Paul I W; Farrall, Martin; Dichgans, Martin; Markus, Hugh S; Bevan, Steve

2014-08-19

To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage. © 2014 American Academy of Neurology.

Ethnic Differences in Ambient Air Pollution and Risk of Acute Ischemic Stroke

PubMed Central

Wing, Jeffrey J.; Adar, Sara D.; Sánchez, Brisa N.; Morgenstern, Lewis B.; Smith, Melinda A.; Lisabeth, Lynda D.

2015-01-01

Objectives To investigate the association between short-term changes in ambient pollution (particulate matter < 2.5μm in aerodynamic diameter (PM2.5) and ozone (O3)) and the risk of ischemic stroke among individuals living in a bi-ethnic community and whether this association is modified by ethnicity. Methods We identified incident ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Associations between PM2.5 (mean 24-hour) and O3 (maximal 8-hour) levels, measured on the same-day and lags of 1-3 days, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. We explored race/ethnicity (Mexican American versus non-Hispanic white) as a modifier by including interaction terms in the models. Results There were 2,948 ischemic strokes with median age 71 years (IQR: 59-80). We observed no overall associations between the air pollutants and odds of ischemic stroke at any lag. When stratified by ethnicity, higher O3 was consistently associated with greater odds of ischemic stroke for non-Hispanic whites, but not for Mexican Americans. Higher PM2.5 was generally associated with lower odds of ischemic stroke for non-Hispanic whites but modestly greater odds for Mexican Americans. Conclusion Ethnic differences in the associations between ischemic stroke and short-term exposures to O3 and PM2.5 were suggested indicating that further study in diverse populations may be warranted. PMID:26451880

Ischemic conditioning-induced endogenous brain protection: Applications Pre-, Per- or Post-Stroke

PubMed Central

Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre- or post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stoke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post- ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those recently reported methodological and mechanistic discoveries in the realm of ischemic conditioning. Due to the varied time differences of ischemic conditioning in different animal models and clinical trials, it is important to define optimal timing to achieve the best conditioning induced neuroprotection. This brings not only an opportunity in treatment of stroke, but challenges as well, as data is just becoming available and the procedures are not yet optimized. The purpose of this review is to shed light on exploiting these ischemic conditioning modalities to protect the cerebrovascular system against diverse injuries and neurodegenerative disorders. PMID:25900056

Pearls: stroke.

PubMed

Wozniak, Marcella A

2010-02-01

The diagnosis of ischemic stroke continues to be a clinical one, although advances in neuroimaging have expanded our understanding of the correlation between clinical symptoms and neuroanatomical localization. Careful neurologic examination allows localization in both neuroanatomical and vascular space. Findings on neuroimaging are then correlated to assess their clinical relevance. Transient ischemic attack is recognized as a warning sign for impending vascular disease, but even less specific transient neurologic symptoms are associated with increased risk. Stroke can occur at any age. For women, the postpartum period is a time of elevated risk for arterial ischemic stroke. (c) Thieme Medical Publishers.

Neurology Concepts: Young Women and Ischemic Stroke-Evaluation and Management in the Emergency Department.

PubMed

Chang, Bernard P; Wira, Charles; Miller, Joseph; Akhter, Murtaza; Barth, Bradley E; Willey, Joshua; Nentwich, Lauren; Madsen, Tracy

2018-01-01

Ischemic stroke is a leading cause of morbidity and mortality worldwide. While the incidence of ischemic stroke is highest in older populations, incidence of ischemic stroke in adults has been rising particularly rapidly among young (e.g., premenopausal) women. The evaluation and timely diagnosis of ischemic stroke in young women presents a challenging situation in the emergency department, due to a range of sex-specific risk factors and to broad differentials. The goals of this concepts paper are to summarize existing knowledge regarding the evaluation and management of young women with ischemic stroke in the acute setting. A panel of six board-certified emergency physicians, one with fellowship training in stroke and one with training in sex- and sex-based medicine, along with one vascular neurologist were coauthors involved in the paper. Each author used various search strategies (e.g., PubMed, PsycINFO, and Google Scholar) for primary research and reviewed articles related to their section. The references were reviewed and evaluated for relevancy and included based on review by the lead authors. Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States. Several risk factors for ischemic stroke exist for young women including oral contraceptive (OCP) use and migraine with aura. Pregnancy and the postpartum period (up to 12 weeks) is also an important transient state during which risks for both ischemic stroke and cerebral hemorrhage are elevated, accounting for 18% of strokes in women under 35. Current evidence regarding the management of acute ischemic stroke in young women is also summarized including use of thrombolytic agents (e.g., tissue plasminogen activator) in both pregnant and nonpregnant individuals. Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population. © 2017 by the Society for Academic Emergency Medicine.

Safety and Time Course of Drip-and-Ship in Treatment of Acute Ischemic Stroke.

PubMed

Ishihara, Hideyuki; Oka, Fumiaki; Oku, Takayuki; Shinoyama, Mizuya; Suehiro, Eiichi; Sugimoto, Kazutaka; Suzuki, Michiyasu

2017-11-01

The drip-and-ship approach allows intravenous tissue plasminogen activator therapy and adjuvant endovascular treatment in acute ischemic stroke, even in rural areas. Here, we examined the safety and time course of the drip-and-ship approach. Fifty consecutive cases treated with the drip-and-ship approach (drip-and-ship group) in June 2009 to March 2016 were retrospectively examined. Changes in mean blood pressure, systemic complications, and neurological complications were compared according to method of transportation. Time courses were compared between drip-and-ship and direct admission groups during the same period. In the drip-and-ship group, 33 and 17 patients were transferred to hospital by ambulance and helicopter, respectively. One patient suffered hemorrhagic infarction during transportation by ambulance. Mean blood pressure change was lower in patients transferred by helicopter than ambulance (<5 mmHg versus 12.2 mmHg, respectively). The mean onset-to-door times in the drip-and-ship and direct admission groups were 71 and 64 minutes, respectively, and mean door-to-needle times were 70 and 47 minutes, respectively (P =.002). Although mean transportation time from the primary stroke hospital to our hospital was 32 minutes, the entry-to-exit time from the primary stroke hospital was 113 minutes. Thereafter, there was an average delay of 100 minutes until reperfusion compared with the direct admission group. Drip-and-ship was relatively safe in this small series. Transportation by helicopter was less stressful for acute ischemic stroke patients. It is important to reduce door-to-needle time and needle-to-departure time in the primary stroke hospital to minimize the time until treatment in cases of acute ischemic stroke. Copyright © 2017. Published by Elsevier Inc.

Social factors influencing hospital arrival time in acute ischemic stroke patients.

PubMed

Iosif, Christina; Papathanasiou, Mathilda; Staboulis, Eleftherios; Gouliamos, Athanasios

2012-04-01

This is a multi-center, hospital-based study aiming to estimate social factors influencing pre-hospital times of arrival in acute ischemic stroke, with a perspective of finding ways to reduce arrival time and to augment the number of patients eligible for intra-arterial thrombolysis. Acute ischemic stroke patients who presented at the emergency units of four major general public hospitals were registered. We assessed information concerning demographics, time of presentation, clinical situation, imaging, treatment, and socioeconomic factors. The sample was divided in two sub-samples, based on the time of arrival since onset of symptoms, and was statistically analyzed. During one calendar year (2005), 907 patients were registered. Among them 34.6% arrived in the first 6 h from symptom onset, 38.7% arrived between 6 and 24 h, 18.1% after 24 h and for 8.6% the time of onset was unknown. Younger age (P = 0.007), transfer with ambulatory service (Ρ = 0.002), living with a mate (Ρ = 0.004), and higher educational level (P < 0.005) were factors which correlated significantly with early arrival at the hospital. Instructing patients at high risk for stroke to live with a housemate appears beneficial for timely arrival at the hospital. The establishment of dedicated acute stroke call and transportation center should improve the percentage of early arrival. A national information campaign is needed to increase the level of awareness of the population concerning beneficial social behaviors and optimal reaction to symptoms of acute ischemic stroke.

Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

PubMed

Shiotani, Satoko; Shimada, Mitsuo; Suehiro, Taketoshi; Soejima, Yuji; Yosizumi, Tomoharu; Shimokawa, Hiroaki; Maehara, Yoshihiko

2004-08-15

Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

Thrombolysis with Intravenous Tissue Plasminogen Activator (rt-PA) Predicts Favorable Discharge Disposition in Patients with Acute Ischemic Stroke

PubMed Central

Ifejika-Jones, Nneka L.; Harun, Nusrat; Mohammed-Rajput, Nareesa A.; Noser, Elizabeth A.; Grotta, James C.

2011-01-01

Background and Purpose Acute ischemic stroke patients receiving IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal disability at three months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Subacute Care (Sub). There are no studies assessing the role of rt-PA use as a predictor of post-stroke disposition. Methods Retrospective analysis of all ischemic stroke patients admitted to the University of Texas Houston Medical School (UTHMS) Stroke Service between Jan 2004 and Oct 2009. Baseline demographics and National Institute of Health Stroke Scale (NIHSS) score were collected. Cerebrovascular disease risk factors were used for risk stratification. Results Home vs. IR, SNF, Sub Of 2225 acute ischemic stroke patients, 1019 were discharged home, 1206 to another level of care. Patients who received rt-PA therapy were 1.9 times more likely to be discharged home (P = <0.0001; OR 1.945, 95% CI 1.538 to 2.459). IR vs. SNF, Sub / SNF vs. Sub Of 1206 acute ischemic stroke patients, 719 patients were discharged to acute IR, 371 were discharged to SNF, 116 to Sub. There were no differences in disposition between patients who received rt-PA therapy. Conclusions Stroke patients who receive IV rt-PA for acute ischemic stroke are more 1.9 times more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. PMID:21293014

The Yin and Yang of innate immunity in stroke.

PubMed

Xu, Xiaomeng; Jiang, Yongjun

2014-01-01

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

Differing effects of cyclosporin a on swelling amplitude and time constant of mitochondria from normal and ischemic rat brain.

PubMed

Wu, Li-Ping; Shen, Fang; Lu, Yuan; Bruce, Iain; Xia, Qiang

2005-01-01

The purpose of this study was to investigate the effect of cyclosporin A on swelling amplitude and time constant of mitochondria isolated from normal and ischemic rat brain and to observe the possible role of the mitochondrial ATP-sensitive potassium channel on mitochondrial permeability transition. Mitochondrial swelling was evaluated by spectrophotometry. Cyclosporin A at 0.5 or 1 microM and diazoxide at 30 microM significantly decreased the swelling amplitude and attenuated the reduction of time constant of mitochondria isolated from normal brain mitochondria induced by 200 microM calcium, an effect abolished by atractyloside at 100 microM. However, cyclosporin A at 5 microM did not affect mitochondrial swelling. In mitochondria from ischemic brain, cyclosporin A at 0.5 microM but not 1 microM significantly decreased mitochondrial swelling amplitude and attenuated the reduction of time constant, which was abolished by atractyloside. Diazoxide had an effect similar to cyclosporin A at 0.5 microM, which was blocked by atractyloside or 5-hydroxydecanoate at 100 microM and 200 microM. Compared with mitochondria isolated from normal brain, those from ischemic brain were more sensitive to cyclosporin A. Activation of the mitochondrial ATP-sensitive potassium channel may be one of the mechanisms by which opening of the mitochondrial permeability transition pore is inhibited.

Refining the ischemic penumbra with topography.

PubMed

Thirugnanachandran, Tharani; Ma, Henry; Singhal, Shaloo; Slater, Lee-Anne; Davis, Stephen M; Donnan, Geoffrey A; Phan, Thanh

2018-04-01

It has been 40 years since the ischemic penumbra was first conceptualized through work on animal models. The topography of penumbra has been portrayed as an infarcted core surrounded by penumbral tissue and an extreme rim of oligemic tissue. This picture has been used in many review articles and textbooks before the advent of modern imaging. In this paper, we review our understanding of the topography of the ischemic penumbra from the initial experimental animal models to current developments with neuroimaging which have helped to further define the temporal and spatial evolution of the penumbra and refine our knowledge. The concept of the penumbra has been successfully applied in clinical trials of endovascular therapies with a time window as long as 24 h from onset. Further, there are reports of "good" outcome even in patients with a large ischemic core. This latter observation of good outcome despite having a large core requires an understanding of the topography of the penumbra and the function of the infarcted regions. It is proposed that future research in this area takes departure from a time-dependent approach to a more individualized tissue and location-based approach.

Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PubMed

Mantel, Irmela; Schalenbourg, Ann; Bergin, Ciara; Petrovic, Aleksandra; Weber, Damien C; Zografos, Leonidas

2014-10-01

To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. Comparative retrospective case series. Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed. Copyright © 2014 Elsevier Inc. All rights reserved.

Stroke: advances in medical therapy and acute stroke intervention.

PubMed

Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

2015-10-01

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

[Results of thrombolyses procedures in acute ischemic cerebral stroke realized in Kraków 2004-2007--Grant Ministry of Science and Information].

PubMed

Popiela, Tadeusz J; Urbanik, Andrzej; Słowik, Agnieszka

2010-01-01

To lower the number of complications of acute cerebral ischemic stroke and to reduce the time of rehabilitation in these patients it is necessary to induce treatment within the first 3 hours of the onset of the stroke. Early intervention however, is possible only in cases with the confirm localized ischemic focus visualized in one of the diagnostic imaging methods. The most widespread is CT, hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of the onset. The study evaluated the effectiveness of early diagnostics of ischemic stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to thrombolysis in the first 3 hours of the onset of the stroke were randomly selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6 hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A study group consisted of 377 patients hospitalized due to ischemic stroke. Of these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra-arterial thrombolysis in 2. Clinical condition substantially improved in 3 patients. Obtained results indicate the necessity to introduce pCT to the routine diagnostics of the acute ischemic stroke. A small number of patients eligible for thrombolysis does not allow to compare the effectiveness of intra-arterial and intravenous thrombolysis, however the project allowed to work out the efficient system of diagnostics and treatment of the acute ischemic stroke in the area of Krakow based on the standards used in the European countries.

Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature.

PubMed

Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

2013-01-01

Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature

NASA Astrophysics Data System (ADS)

Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

2013-01-01

Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

Time trends in patient characteristics treated on acute stroke-units: results from the Austrian Stroke Unit Registry 2003-2011.

PubMed

Teuschl, Yvonne; Brainin, Michael; Matz, Karl; Dachenhausen, Alexandra; Ferrari, Julia; Seyfang, Leonhard; Lang, Wilfried

2013-04-01

Demographic changes, increased awareness of vascular risk factors, better diagnostic, progress in medical care, and increasing primary stroke prevention influence the profile of patients admitted to stroke-units. Changes in patient population and stroke type have important consequences on outcome and management at stroke-units. Data from the national database of the Austrian Stroke Unit Registry were analyzed for time-trends in demography, risk factors, cause, and stroke severity. Data of 48 038 ischemic and 5088 hemorrhagic strokes were analyzed. Between 2003 and 2011, median age increased significantly for ischemic strokes from 68 to 71 years in men and from 76 to 78 years in women, respectively. Ischemic stroke patients showed significantly increased rates of hypertension, hypercholesterolemia, and atrial fibrillation. In hemorrhagic strokes an increase for hypercholesterolemia and cardiac diseases other than atrial fibrillation and myocardial infarction were only found in men. A small but significant decrease in stroke severity was found for ischemic strokes from 4 to 3 points on the National Institutes of Health Stroke Scale in men and from 5 to 4 in women, and for hemorrhagic strokes from 9 to 6 points in men and from 9 to 7 in women. Cardioembolic strokes increased slightly, whereas macroangiopathy decreased. Significant time trends were seen for characteristics of ischemic and hemorrhagic stroke patients admitted to acute stroke-units in Austria. These include trends for older age and toward milder strokes with more cardioembolic causes. This signals a need for increased resources for managing multimorbidity and enabling early mobilization.

Retinal protective effects of topically administered agmatine on ischemic ocular injury caused by transient occlusion of the ophthalmic artery

PubMed Central

Hong, S.; Hara, H.; Shimazawa, M.; Hyakkoku, K.; Kim, C.Y.; Seong, G.J.

2012-01-01

Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g) for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6), a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6), a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P < 0.001; Kruskal-Wallis test). Overall, we determined that topical agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases. PMID:22331138

A Linear Temporal Increase in Thrombin Activity and Loss of Its Receptor in Mouse Brain following Ischemic Stroke.

PubMed

Bushi, Doron; Stein, Efrat Shavit; Golderman, Valery; Feingold, Ekaterina; Gera, Orna; Chapman, Joab; Tanne, David

2017-01-01

Brain thrombin activity is increased following acute ischemic stroke and may play a pathogenic role through the protease-activated receptor 1 (PAR1). In order to better assess these factors, we obtained a novel detailed temporal and spatial profile of thrombin activity in a mouse model of permanent middle cerebral artery occlusion (pMCAo). Thrombin activity was measured by fluorescence spectroscopy on coronal slices taken from the ipsilateral and contralateral hemispheres 2, 5, and 24 h following pMCAo ( n  = 5, 6, 5 mice, respectively). Its spatial distribution was determined by punch samples taken from the ischemic core and penumbra and further confirmed using an enzyme histochemistry technique ( n  = 4). Levels of PAR1 were determined using western blot. Two hours following pMCAo, thrombin activity in the stroke core was already significantly higher than the contralateral area (11 ± 5 vs. 2 ± 1 mU/ml). At 5 and 24 h, thrombin activity continued to rise linearly ( r  = 0.998, p  = 0.001) and to expand in the ischemic hemisphere beyond the ischemic core reaching deleterious levels of 271 ± 117 and 123 ± 14 mU/ml (mean ± SEM) in the basal ganglia and ischemic cortex, respectively. The peak elevation of thrombin activity in the ischemic core that was confirmed by fluorescence histochemistry was in good correlation with the infarcts areas. PAR1 levels in the ischemic core decreased as stroke progressed and thrombin activity increased. In conclusion, there is a time- and space-related increase in brain thrombin activity in acute ischemic stroke that is closely related to the progression of brain damage. These results may be useful in the development of therapeutic strategies for ischemic stroke that involve the thrombin-PAR1 pathway in order to prevent secondary thrombin related brain damage.

Large arterial occlusive strokes as a medical emergency: need to accurately predict clot location.

PubMed

Vanacker, Peter; Faouzi, Mohamed; Eskandari, Ashraf; Maeder, Philippe; Meuli, Reto; Michel, Patrik

2017-10-01

Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting. Patients enrolled in ASTRAL registry with acute ischemic stroke and computed tomography (CT)-angiography within 12 h of stroke onset were selected and categorized according to occlusion site. Easily accessible variables were used in a multivariate analysis. Of 1645 patients enrolled, a significant proportion (46.2%) had a large vessel occlusion in the ischemic territory. The main clinical predictors of any arterial occlusion were in-hospital stroke [odd ratios (OR) 2.1, 95% confidence interval 1.4-3.1], higher initial National Institute of Health Stroke Scale (OR 1.1, 1.1-1.2), presence of visual field defects (OR 1.9, 1.3-2.6), dysarthria (OR 1.4, 1.0-1.9), or hemineglect (OR 2.0, 1.4-2.8) at admission and atrial fibrillation (OR 1.7, 1.2-2.3). Further, the following radiological predictors were identified: time-to-imaging (OR 0.9, 0.9-1.0), early ischemic changes (OR 2.3, 1.7-3.2), and silent lesions on CT (OR 0.7, 0.5-1.0). The area under curve for this analysis was 0.85. Looking at different occlusion sites, National Institute of Health Stroke Scale and early ischemic changes on CT were independent predictors in all subgroups. Neurological deficits, stroke risk factors, and CT findings accurately identify acute ischemic stroke patients at risk of symptomatic vessel occlusion. Predicting the presence of these occlusions may impact emergency stroke care in regions with limited access to noninvasive vascular imaging.

Hypothermic machine perfusion permits extended cold ischemia times with improved early graft function.

PubMed

Guy, Alison; McGrogan, Damian; Inston, Nicholas; Ready, Andrew

2015-04-01

The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time. Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list. There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications. This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

PubMed

Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen

2015-01-01

Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke.

PubMed

Ji, Ya-Bin; Wu, Yong-Ming; Ji, Zhong; Song, Wei; Xu, Sui-Yi; Wang, Yao; Pan, Su-Yue

2012-07-01

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI). Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated. Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method. Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

PubMed

Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

2017-09-01

Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart.

PubMed

Evans, Cameron W; Iyer, K Swaminathan; Hool, Livia C

2016-04-01

Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent examples of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia.

Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats

PubMed Central

Yang, Shuai; Abbott, Geoffrey W.; Gao, Wei Dong; Liu, Jin; Luo, Chaozhi

2017-01-01

Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway. NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury. However, it is unclear whether ischemic conditioning of visceral organs such as the liver, the largest metabolic organ in the body, can produce cardioprotection. This is the first study to show the cardioprotective effect of remote liver ischemic conditioning in a rat model of myocardial I/R injury. We also, for the first time, demonstrated these protective properties are associated with glycogen synthase kinase-3β-dependent cell-survival signaling pathway. PMID:28153944

Air Pollution and Subtypes, Severity and Vulnerability to Ischemic Stroke—A Population Based Case-Crossover Study

PubMed Central

Maheswaran, Ravi; Pearson, Tim; Beevers, Sean D.; Campbell, Michael J.; Wolfe, Charles D.

2016-01-01

Background and Purpose Few studies have examined the association between air pollutants and ischemic stroke subtypes. We examined acute effects of outdoor air pollutants (PM10, NO2, O3, CO, SO2) on subtypes and severity of incident ischemic stroke and investigated if pre-existing risk factors increased susceptibility. Methods We used a time stratified case-crossover study and stroke cases from the South London Stroke Register set up to capture all incident cases of first ever stroke occurring amongst residents in a geographically defined area. The Oxford clinical and TOAST etiological classifications were used to classify subtypes. A pragmatic clinical classification system was used to assess severity. Air pollution concentrations from the nearest background air pollution monitoring stations to patients’ residential postcode centroids were used. Lags from 0 to 6 days were investigated. Results There were 2590 incident cases of ischemic stroke (1995–2006). While there were associations at various lag times with several pollutants, overall, there was no consistent pattern between exposure and risk of ischemic stroke subtypes or severity. The possible exception was the association between NO2 exposure and small vessel disease stroke—adjusted odds ratio of 1.51 (1.12–2.02) associated with an inter-quartile range increase in the lag 0–6 day average for NO2. There were no clear associations in relation to pre-existing risk factors. Conclusions Overall, we found little consistent evidence of association between air pollutants and ischemic stroke subtypes and severity. There was however a suggestion that increasing NO2 exposure might be associated with higher risk of stroke caused by cerebrovascular small vessel disease. PMID:27362783

Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

PubMed

Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

2015-11-01

Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer

PubMed Central

Addison, Daniel; Lawler, Patrick R.; Emami, Hamed; Janjua, Sumbal A.; Staziaki, Pedro V.; Hallett, Travis R.; Hennessy, Orla; Lee, Hang; Szilveszter, Bálint; Lu, Michael; Mousavi, Negar; Nayor, Matthew G.; Delling, Francesca N.; Romero, Javier M.; Wirth, Lori J.; Chan, Annie W.; Hoffmann, Udo; Neilan, Tomas G.

2018-01-01

Background and Purpose Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. Methods From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. Results The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). Conclusions Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA. PMID:29402065

Regulation of Therapeutic Hypothermia on Inflammatory Cytokines, Microglia Polarization, Migration and Functional Recovery after Ischemic Stroke in Mice

PubMed Central

Lee, Jin Hwan; Wei, Zheng Z; Cao, Wenyuan; Won, Soonmi; Gu, Xiaohuan; Winter, Megan; Dix, Thomas A.; Wei, Ling; Yu, Shan Ping

2016-01-01

Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models. To further characterize the mechanism of TH-induced brain protection, we examined the effect of TH (at ±33°C for 6 hrs) induced by the NTR1 agonist HPI-201 or physical (ice/cold air) cooling on inflammatory responses after ischemic stroke in mice and oxygen glucose deprivation (OGD) in cortical neuronal cultures. Seven days after focal cortical ischemia, microglia activation in the penumbra reached a peak level, which was significantly attenuated by TH treatments commenced 30 min after stroke. The TH treatment decreased the expression of M1 type reactive factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, IL-23, and inducible nitric oxide synthase (iNOS) measured by RT-PCR and Western blot analyses. Meanwhile, TH treatments increased the expression of M2 type reactive factors including IL-10, Fizz1, Ym1, and arginase-1. In the ischemic brain and in cortical neuronal/BV2 microglia cultures subjected to OGD, TH attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α), two key chemokines in the regulation of microglia activation and infiltration. Consistently, physical cooling during OGD significantly decreased microglia migration 16 hrs after OGD. Finally, TH improved functional recovery at 1, 3, and 7 days after stroke. This study reveals the first evidence for hypothermia mediated regulation on inflammatory factor expression, microglia polarization, migration and indicates that the anti-inflammatory effect is an important mechanism underlying the brain protective effects of a TH therapy. PMID:27659107

Biliary Complications after Liver Transplantation from Donation after Cardiac Death Donors: An Analysis of Risk Factors and Long Term Outcomes from a Single Center

PubMed Central

Foley, David P.; Fernandez, Luis A.; Leverson, Glen; Anderson, Michael; Mezrich, Joshua; Sollinger, Hans W.; D’Alessandro, Anthony

2011-01-01

Objective This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from donation after cardiac death (DCD) donors. Summary Background Data Recent enthusiasm toward increased use of DCD donor livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined. Methods We performed a retrospective review of 1157 donation after brain death (DBD) and 87 DCD liver transplants performed between January 1, 1993 and December 31, 2008. Patient and graft survivals, and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors. Results Patient survival was significantly lower in the DCD group compared to the DBD group at 1, 5, 10 and 15 years (DCD: 84%, 68%, 54%, 54% vs. DBD: 91%, 81%, 67%, 58%, p<0.01). Graft survival was also significantly lower in the DCD group compared to the DBD group at 1, 5, 10 and 15 years (DCD: 69%, 56%, 43%, 43% vs. DBD: 86%, 76%, 60%, 51%, p<0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs. DBD: 26%, p<0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs. DBD: 1%, p<0.01) were significantly higher in the DCD group. Donor age (HR: 1.04, p<0.01) and donor age >40 years (HR: 3.13, p < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed cold ischemic time (CIT) >8 hours (HR: 2.46, p=0.05), donor age >40 (HR: 2.90, p< 0.01) significantly increased the risk of IC. Conclusions Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared to DBD liver transplants. Donor age and CIT >8 hours are the strongest predictors for the development of ischemic cholangiopathy. Careful selection of younger DCD donors and minimizing CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donor livers. PMID:21475025

Clinical Features of Ocular Ischemic Syndrome and Risk Factors for Neovascular Glaucoma.

PubMed

Kim, Yung Hui; Sung, Mi Sun; Park, Sang Woo

2017-08-01

We aimed to examine the clinical features and prognosis of ocular ischemic syndrome and to investigate the risk factors for the development of neovascular glaucoma (NVG). The medical records from 25 patients (25 eyes) who were diagnosed with ocular ischemic syndrome were retrospectively analyzed. We recorded the length of time between symptom onset and diagnosis, visual acuity, intraocular pressure, clinical findings of the anterior and posterior segments of the eye, fluorescein angiography, systemic diseases, smoking history, and the extent of any ipsilateral carotid artery stenosis. The risk factors for NVG in patients with ocular ischemic syndrome were investigated. The mean age was 67.9 ± 12.5 years, and 21 men and 4 women were included in this study. At initial examination, the mean logarithm of the minimum angle of resolution (logMAR) was 2.02 ± 1.26, and the mean intraocular pressure was 21.0 ± 10.3 mmHg. Among 25 eyes of the 25 patients, NVG occurred in 17 eyes after a mean period of 12.6 ± 14.0 months. The length of time between symptom onset and diagnosis (p = 0.025) and the extent of ipsilateral carotid artery stenosis (p = 0.032) were identified as significant risk factors for NVG. At the final follow-up, the mean logMAR visual acuity was 3.13 ± 1.24, showing a poor prognosis regardless of whether NVG occurred. Overall, the prognosis for ocular ischemic syndrome is very poor. The risk of NVG increases with the length of time between symptom onset and diagnosis, as well as with the severity of ipsilateral carotid artery stenosis. © 2017 The Korean Ophthalmological Society

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

PubMed Central

Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

Premature Ventricular Complexes on Screening Electrocardiogram and Risk of Ischemic Stroke

PubMed Central

Agarwal, Sunil K.; Chao, Jennifer; Peace, Frederick; Judd, Suzanne E.; Kissela, Brett; Kleindorfer, Dawn; Howard, Virginia J.; Howard, George; Soliman, Elsayed Z.

2015-01-01

Background and Purpose Premature ventricular complexes (PVCs) detected from long-term electrocardiogram (ECG) recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. Methods This analysis included 24,460 participants (age 64.5+9.3 years, 55.1% Female, 40.0% African Americans) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. Results A total of 1,415 (5.8%) participants had at least one PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a Cox Proportional hazards model adjusted for age, sex, race, geographic region, education, prior heart disease, systolic blood pressure, blood pressure lowering medications, current smoking, diabetes, left ventricular hypertrophy by ECG, aspirin use and warfarin use, presence of PVCs was associated with 38% increased risk of ischemic stroke (HR (95% CI): 1.38 (1.05, 1.81)). Conclusions PVCs are common on routine screening ECGs, and are associated with an increased risk of ischemic stroke. PMID:25873602

Effect of non-invasive remote ischemic preconditioning on intra-renal perfusion in volunteers.

PubMed

Robert, René; Vinet, Mathieu; Jamet, Angéline; Coudroy, Rémi

2017-06-01

Remote ischemic preconditioning may attenuate renal injury and protect the kidney during subsequent inflammatory or ischemic stress. However, the mechanism of such a protection is not well understood. The aim of this study was to investigate the impact of remote ischemic preconditioning on renal resistivity index (RRI) in nine healthy volunteers. In six volunteers, four cycles of 4-min inflation of a blood pressure cuff were applied to one upper arm, followed by 4-min reperfusion with the cuff deflated. RRI was determined using Doppler echography during each cuff deflated period. Measures were also performed in three volunteers without preconditioning. The median value of RRI significantly decreased progressively from 0.59 [0.53-0.62] before the remote conditioning (baseline) to 0.49 [0.46-0.53] at the end of the experiment (p < 0.001) whereas there was no change in controls. In this study, for the first time, we have clearly shown in a small group of subjects that remote ischemic preconditioning can induce a significantly decrease in RRI through increased intra-renal perfusion.

Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

PubMed

Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

2013-05-01

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro.

PubMed

Bhuiyan, Mohammad Iqbal Hossain; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae

2011-06-01

Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD imposed 12 h before lethal 3-h OGD. The time-course studies of relative phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of their involvement in ischemic tolerance. However, there were significant increases in Akt phosphorylation levels during the reperfusion period following preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and GSK-3β were also found to be inactivated during that reperfusion period. Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.

Temporal trends in stroke incidence in South Asian, Chinese and white patients: A population based analysis.

PubMed

Khan, Nadia A; McAlister, Finlay A; Pilote, Louise; Palepu, Anita; Quan, Hude; Hill, Michael D; Fang, Jiming; Kapral, Moira K

2017-01-01

Little is known about potential ethnic differences in stroke incidence. We compared incidence and time trends of ischemic stroke and primary intracerebral hemorrhage in South Asian, Chinese and white persons in a population-based study. Population based census and administrative data analysis in the provinces of Ontario and British Columbia, Canada using validated ICD 9/ICD 10 coding for acute ischemic and hemorrhagic stroke (1997-2010). There were 3290 South Asians, 4444 Chinese and 160944 white patients with acute ischemic stroke and 535 South Asian, 1376 Chinese and 21842 white patients with intracerebral hemorrhage. South Asians were younger than whites at onset of stroke (70 vs. 74 years for ischemic and 67 vs. 71 years for hemorrhagic stroke). Age and sex adjusted ischemic stroke incidence in 2010 was 43% lower in Chinese and 63% lower in South Asian than in White patients. Age and sex adjusted intracerebral hemorrhage incidence was 18% higher in Chinese patients, and 66% lower in South Asian relative to white patients. Stroke incidence declined in all ethnic groups (relative reduction 69% in South Asians, 25% in Chinese, and 34% in white patients for ischemic stroke and for intracerebral hemorrhage, 79% for South Asians, 51% for Chinese and 30% in white patients). Although stroke rates declined across all ethnic groups, these rates differed significantly by ethnicity. Further study is needed to understand mechanisms underlying the higher ischemic stroke incidence in white patients and intracerebral hemorrhage in Chinese patients.

Impact of remote ischemic preconditioning on wound healing in small bowel anastomoses

PubMed Central

Holzner, Philipp Anton; Kulemann, Birte; Kuesters, Simon; Timme, Sylvia; Hoeppner, Jens; Hopt, Ulrich Theodor; Marjanovic, Goran

2011-01-01

AIM: To investigate the influence of remote ischemic preconditioning (RIPC) on anastomotic integrity. METHODS: Sixty male Wistar rats were randomized to six groups. The control group (n = 10) had an end-to-end ileal anastomosis without RIPC. The preconditioned groups (n = 34) varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis (n = 9). On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosal ischemic injury were collected. The data are given as median (range). RESULTS: On postoperative day 4, median bursting pressure was 124 mmHg (60-146 mmHg) in the control group. The experimental groups did not show a statistically significant difference (P > 0.05). Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION: RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning. PMID:21455330

Beneficial effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in the rat.

PubMed

Magyar, Zsuzsanna; Mester, Anita; Nadubinszky, Gabor; Varga, Gabor; Ghanem, Souleiman; Somogyi, Viktoria; Tanczos, Bence; Deak, Adam; Bidiga, Laszlo; Oltean, Mihai; Peto, Katalin; Nemeth, Norbert

2018-04-14

Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results.

The importance of selected spices in cardiovascular diseases.

PubMed

Kulczyński, Bartosz; Gramza-Michałowska, Anna

2016-11-14

Cardiovascular diseases are the leading cause of death worldwide. Literature data indicate that, due to these diseases, approximately 17.5 million people died in 2012. Types of cardiovascular disease include ischemic heart disease, cerebrovascular disease, peripheral vascular disease, congenital heart disease, rheumatic heart disease, cardiomyopathy and arrhythmia. Proper nutrition is an important factor in reducing the risk of cardiovascular events. An interesting element of our diets is spices. For thousands of years, they have been used in the treatment of many diseases: bacterial infections, coughs, colds, and liver diseases. Many studies also demonstrate their antioxidant, chemopreventive, anti-inflammatory and immunomodulatory properties. This paper focuses on discussing the importance of selected spices (garlic, cinnamon, ginger, coriander and turmeric) in the prevention and treatment of cardiovascular diseases.

Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

PubMed

Purrucker, Jan C; Haas, Kirsten; Rizos, Timolaos; Khan, Shujah; Poli, Sven; Kraft, Peter; Kleinschnitz, Christoph; Dziewas, Rainer; Binder, Andreas; Palm, Frederick; Jander, Sebastian; Soda, Hassan; Heuschmann, Peter U; Veltkamp, Roland

2017-01-01

In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke. Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored. In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients. NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797. © 2016 American Heart Association, Inc.

Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study.

PubMed

Madsen, Tracy E; Khoury, Jane; Alwell, Kathleen; Moomaw, Charles J; Rademacher, Eric; Flaherty, Matthew L; Woo, Daniel; Mackey, Jason; De Los Rios La Rosa, Felipe; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Broderick, Joseph P; Kissela, Brett M; Kleindorfer, Dawn

2017-09-05

Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993-June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p < 0.001). Incidence of all strokes decreased over time in men (263 [confidence interval 246-281] to 192 [179-205], p < 0.001) but not in women (217 [205-230] to 198 [187-210], p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223-257] to 165 [153-177], p < 0.01; women, 193 [181-205] to 173 [162-184], p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men. © 2017 American Academy of Neurology.

Computed tomography perfusion imaging may predict cognitive impairment in patients with first-time anterior circulation transient ischemic attack.

PubMed

Wang, Jun; Li, Yunming; Zheng, Bo; Wang, Jian; Wang, Zhiqiang; Duan, Dan; Li, Yuxia; Wang, Qingsong

2016-04-01

To determine whether computed tomography perfusion imaging (CTPI)-derived parameters are associated with vascular cognitive impairment (VCI) in patients with transient ischemic attack (TIA). Patients with first-time anterior circulation TIA (diagnosed within 24 h of onset) and normal cognition, treated between August 2009 and August 2014 at the Department of Neurology of Chengdu Military General Hospital, China, were analyzed retrospectively. Patients underwent whole-brain CTPI within 1 week of TIA to detect cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) in the ischemic region. Based on cognitive function assessment 4 weeks after TIA, using the Montreal cognitive assessment (MoCA) and mini mental state examination, the patients were divided into control and VCI groups. CTPI parameters and other clinical data were compared between groups, and Spearman's correlation analysis used to identify associations between cognitive scores and CTPI parameters in the VCI group. 50 patients (25 per group; aged 55-72 years) were included. Patient age, gender, smoking status, alcohol consumption, educational level, time from TIA onset to admission, time from TIA onset to CTPI, and prevalence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation and hyperhomocysteinemia did not differ between groups. Both groups showed TTP and MTT prolongation, CBF reduction, but no change in CBV in the ischemic region; these changes were significantly larger in the VCI group (P < 0.05). MTT correlated negatively with MoCA score (r = -0.51, P = 0.009). CTPI could facilitate early diagnosis of VCI in patients with anterior circulation TIA.

Comparison of Pfannenstiel or Extended Iliac Port Site Kidney Extraction in Laparoscopic Donor Nephrectomy: Do We Have Consensus?

PubMed

Iemsupakkul, Paiboon; Kongchareonsombat, Wisoot; Kijvikai, Kittinut

2017-04-01

Our objective was to compare the outcomes of the different extraction sites between extended iliac port site incision and Pfannenstiel incision during laparoscopic donor nephrectomy. We prospectively evaluated patients who underwent laparoscopic donor nephrectomy from June 2014 to March 2015 at our institution. Perioperative parameters were included, with particular reference to warm ischemic time. The other parameters recorded included operative time, blood loss, hospital stay, analgesic requirement, and cosmetic results. We analyzed a total of 41 patients. Kidney retrieval site of each patient was made randomly. Extraction sites were done by using extended iliac port site incisions in 23 patients and by Pfannenstiel incision in 18 patients. Mean warm ischemic time was 4.09 minutes with extended iliac port site incision versus 4.94 minutes with Pfannenstiel incision (P = .04). Mean operative time, blood loss, hospital stay, and analgesic requirements were comparable between the 2 groups. Mean cosmetic score was 10.39 with extended iliac port site versus 12.06 with Pfannenstiel incision. Extraction with extended iliac port site incision had significantly less warm ischemic time than Pfannenstiel incision in laparoscopic donor nephrectomy. It was also not inferior to Pfannenstiel incision regarding the other.

A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds

PubMed Central

Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K.

2015-01-01

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. PMID:25224310

Adenosine Diphosphate-Induced Platelet-Fibrin Clot Strength: A New Thrombelastographic Indicator of Long-Term Post-Stenting Ischemic Events

PubMed Central

Gurbel, Paul A.; Bliden, Kevin P.; Navickas, Irene A.; Mahla, Elizabeth; Dichiara, Joseph; Suarez, Thomas A.; Antonino, Mark J.; Tantry, Udaya S.; Cohen, Eli

2010-01-01

Background Post-stenting ischemic events occur despite dual antiplatelet therapy suggesting that a “one size fits all” antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. Methods We investigated the prognostic utility of the strength of ADP-induced (MAADP) and thrombin-induced (MATHROMBIN) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTAADP) in 225 serial patients following elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over three-years. Results Overall, 59 (26 %) first ischemic events occurred. Patients with ischemic events had higher MAADP, MATHROMBIN, and LTAADP (p<0.0001 for all comparisons). By receiver operating characteristic curve analysis, MAADP > 47mm had the best predictive value of long-term ischemic events compared to other measurements (p<0.0001) with an area under the curve = 0.84 [95% CI 0.78 – 0.89, p < 0.0001]. The univariate Cox proportional hazards model identified MAADP >47mm, MATHROMBIN >69mm, and LTA ADP >34% as significant independent predictors of first ischemic events at the three-year time point, with hazard ratios of 10.3 (p<0.0001), 3.8 (p<0.0001), and 4.8 (p<0.0001) respectively. Fifteen bleeding events occurred. Receiver operator characteristic curve and quartile analysis suggest MAADP ≤ 31 as a predictive value for bleeding. Conclusion This study is the first demonstration of the prognostic utility of MAADP in predicting long term event occurrence following stenting. The quantitative assessment of ADP-stimulated platelet-fibrin clot strength measured by thrombelastography can serve as a future tool in investigations of personalized antiplatelet treatment designed to reduce ischemic events and bleeding. PMID:20691842

Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events.

PubMed

Gurbel, Paul A; Bliden, Kevin P; Navickas, Irene A; Mahla, Elizabeth; Dichiara, Joseph; Suarez, Thomas A; Antonino, Mark J; Tantry, Udaya S; Cohen, Eli

2010-08-01

Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a "one size fits all" antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)-induced (MA(ADP)) and thrombin-induced (MA(THROMBIN)) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTA(ADP)) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years. Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MA(ADP), MA(THROMBIN), and LTA(ADP) (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MA(ADP) >47 mm had the best predictive value of long-term ischemic events compared with other measurements (P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MA(ADP) >47 mm, MA(THROMBIN) >69 mm, and LTA(ADP) >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P < .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MA(ADP)

Normobaric hyperoxia retards the evolution of ischemic brain tissue toward infarction in a rat model of transient focal cerebral ischemia.

PubMed

Xu, Ji; Zhang, Yuan; Liang, Zhouyuan; Wang, Ting; Li, Weiping; Ren, Lijie; Huang, Shaonong; Liu, Wenlan

2016-01-01

Oxygen therapy has been long considered a logical therapy for ischemic stroke. Our previous studies showed that normobaric hyperoxia (normobaric hyperoxia (NBO), 95% O2 with 5% CO2) treatment during ischemia reduced ischemic neuronal death and cerebromicrovascular injury in animal stroke models. In this study, we studied the effects of NBO on the evolution of ischemic brain tissue to infarction in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery (MCAO), followed by 3 or 22.5 h of reperfusion. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the longitudinal evolution of tissue infarction. Results： In normoxic rats, MCA-supplied cortical and striatal tissue was infarcted after 90-min MCAO with 22.5 h of reperfusion. NBO-treated rats showed a 61.4% reduction in infarct size and tissue infarction mainly occurred in the ischemic striatum. When infarction was assessed at an earlier time point, i.e. at 3 h of reperfusion, normoxic rats showed significantly smaller but mature infarction (no TTC staining, white color), with the infarction mainly occurring in the striatum. Unexpectedly, NBO-treated rats only showed immature lesion (partially stained by TTC, light white color) in the ischemic striatum, indicating that NBO treatment also retarded the process of neuronal death in the ischemic core. Of note, NBO-preserved striatal tissue underwent infarction after prolonged reperfusion. Conclusions： Our results demonstrate that NBO treatment given during cerebral ischemia retards the evolution of ischemic brain tissue toward infarction and NBO-preserved cortical tissue survives better than NBO-preserved striatal tissue during the phase of reperfusion.

Does acupuncture ameliorate motor impairment after stroke? An assessment using the CatWalk gait system.

PubMed

Cao, Yan; Sun, Ning; Yang, Jing-Wen; Zheng, Yang; Zhu, Wen; Zhang, Zhen-Hua; Wang, Xue-Rui; Shi, Guang-Xia; Liu, Cun-Zhi

2017-07-01

The effect of acupuncture on gait deficits after stroke is uncertain. This animal study was designed to determine whether acupuncture improves gait impairment following experimentally induced ischemic stroke. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in rats. After 7 days' of acupuncture treatment, assessment of gait changes using the CatWalk automated gait analysis system was performed. Comparison of the CatWalk gait parameters among the groups showed that gait function was impaired after ischemic stroke and acupuncture treatment was effective in improving a variety of gait parameters including intensity, stance and swing time, swing speed and stride length at postoperative day 8. This study demonstrates a beneficial effect of acupuncture on gait impairment in rats following ischemic stroke. Further studies aimed to investigate the effects of acupuncture at different stages during stroke using the CatWalk system are required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

PubMed

Takeda, Seiichi; Toda, Takao; Nakamura, Kazuki

2016-01-01

We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Deep cerebral microbleeds are negatively associated with HDL-C in elderly first-time ischemic stroke patients.

PubMed

Igase, Michiya; Kohara, Katsuhiko; Igase, Keiji; Yamashita, Shiro; Fujisawa, Mutsuo; Katagi, Ryosuke; Miki, Tetsuro

2013-02-15

Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients. Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs. One hundred and sixteen patients with a mean age of 70±10years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH>2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta=-0.06, p=0.002) and PVH grade >2 (beta=3.40, p=0.005) were independent determinants of deep CMBs. Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke. Copyright © 2012 Elsevier B.V. All rights reserved.

Bedside assistance in freehand ultrasonic diagnosis by real-time visual feedback of 3D scatter diagram of pulsatile tissue-motion

NASA Astrophysics Data System (ADS)

Fukuzawa, M.; Kawata, K.; Nakamori, N.; Kitsunezuka, Y.

2011-03-01

By real-time visual feedback of 3D scatter diagram of pulsatile tissue-motion, freehand ultrasonic diagnosis of neonatal ischemic diseases has been assisted at the bedside. The 2D ultrasonic movie was taken with a conventional ultrasonic apparatus (ATL HDI5000) and ultrasonic probes of 5-7 MHz with the compact tilt-sensor to measure the probe orientation. The real-time 3D visualization was realized by developing an extended version of the PC-based visualization system. The software was originally developed on the DirectX platform and optimized with the streaming SIMD extensions. The 3D scatter diagram of the latest pulsatile tissues has been continuously generated and visualized as projection image with the ultrasonic movie in the current section more than 15 fps. It revealed the 3D structure of pulsatile tissues such as middle and posterior cerebral arteries, Willis ring and cerebellar arteries, in which pediatricians have great interests in the blood flow because asphyxiated and/or low-birth-weight neonates have a high risk of ischemic diseases such as hypoxic-ischemic encephalopathy and periventricular leukomalacia. Since the pulsatile tissue-motion is due to local blood flow, it can be concluded that the system developed in this work is very useful to assist freehand ultrasonic diagnosis of ischemic diseases in the neonatal cranium.

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Fish oil and olive oil-rich diets modify ozone-induced ...

EPA Pesticide Factsheets

Rationale: Air pollution exposure has been associated with adverse cardiovascular health effects. Our clinical studies suggest that fish oil (FO) and olive oil (OO) supplementations attenuate the cardiovascular responses to inhaled concentrated ambient particles. This study was designed to examine the cardiovascular effects of ozone and the efficacy of FO and OO-rich diets in attenuating these effects of ozone exposure in rats. Methods: Male Wistar Kyoto rats were fed either a normal diet (ND), or a diet enriched with 6% FO or OO starting at 4 weeks of age. Eight weeks following the start of the diet, animals were exposed to filtered air (FA) or 0.8 ppm ozone, 4 hr/day for 2 consecutive days. Immediately after exposure, cardiac responses were assessed ex vivo using a Langendorff heart preparation with a protocol consisting of 20 min of global ischemia followed by 2 hr reperfusion. Cardiac function was measured as the index of left-ventricular developed pressure (LVDP) and contractility (dP/dtmax and dP/dtmin) before ischemia. Upon reperfusion after ischemia, the recovery of post-ischemic LVDP and infarct size were examined. Results: The pre-ischemic LVDP, dP/dtmax, and dP/dtmin were lower after ozone exposure when compared to the FA control in the rats fed ND but not FO and OO. OO diet shortened the time to ischemic contracture of the hearts after FA exposure compared to ND. Ozone exposure increased pre-ischemic heart rate and the time to ischemic contractur

First experience of liver transplantation with type 2 donation after cardiac death in France.

PubMed

Savier, Eric; Dondero, Federica; Vibert, Eric; Eyraud, Daniel; Brisson, Hélène; Riou, Bruno; Fieux, Fabienne; Naili-Kortaia, Salima; Castaing, Denis; Rouby, Jean-Jacques; Langeron, Olivier; Dokmak, Safi; Hannoun, Laurent; Vaillant, Jean-Christophe

2015-05-01

Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed. © 2015 American Association for the Study of Liver Diseases.

Impact of mobile intensive care unit use on total ischemic time and clinical outcomes in ST-elevation myocardial infarction patients - real-world data from the Acute Coronary Syndrome Israeli Survey.

PubMed

Koifman, Edward; Beigel, Roy; Iakobishvili, Zaza; Shlomo, Nir; Biton, Yitschak; Sabbag, Avi; Asher, Elad; Atar, Shaul; Gottlieb, Shmuel; Alcalai, Ronny; Zahger, Doron; Segev, Amit; Goldenberg, Ilan; Strugo, Rafael; Matetzky, Shlomi

2017-01-01

Ischemic time has prognostic importance in ST-elevation myocardial infarction patients. Mobile intensive care unit use can reduce components of total ischemic time by appropriate triage of ST-elevation myocardial infarction patients. Data from the Acute Coronary Survey in Israel registry 2000-2010 were analyzed to evaluate factors associated with mobile intensive care unit use and its impact on total ischemic time and patient outcomes. The study comprised 5474 ST-elevation myocardial infarction patients enrolled in the Acute Coronary Survey in Israel registry, of whom 46% ( n=2538) arrived via mobile intensive care units. There was a significant increase in rates of mobile intensive care unit utilization from 36% in 2000 to over 50% in 2010 ( p<0.001). Independent predictors of mobile intensive care unit use were Killip>1 (odds ratio=1.32, p<0.001), the presence of cardiac arrest (odds ratio=1.44, p=0.02), and a systolic blood pressure <100 mm Hg (odds ratio=2.01, p<0.001) at presentation. Patients arriving via mobile intensive care units benefitted from increased rates of primary reperfusion therapy (odds ratio=1.58, p<0.001). Among ST-elevation myocardial infarction patients undergoing primary reperfusion, those arriving by mobile intensive care unit benefitted from shorter median total ischemic time compared with non-mobile intensive care unit patients (175 (interquartile range 120-262) vs 195 (interquartile range 130-333) min, respectively ( p<0.001)). Upon a multivariate analysis, mobile intensive care unit use was the most important predictor in achieving door-to-balloon time <90 min (odds ratio=2.56, p<0.001) and door-to-needle time <30 min (odds ratio=2.96, p<0.001). One-year mortality rates were 10.7% in both groups (log-rank p-value=0.98), however inverse propensity weight model, adjusted for significant differences between both groups, revealed a significant reduction in one-year mortality in favor of the mobile intensive care unit group (odds ratio=0.79, 95% confidence interval (0.66-0.94), p=0.01). Among patients with ST-elevation myocardial infarction, the utilization of mobile intensive care units is associated with increased rates of primary reperfusion, a reduction in the time interval to reperfusion, and a reduction in one-year adjusted mortality.

Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation.

PubMed

Leger, Kasey J; Baker, K Scott; Cushing-Haugen, Kara L; Flowers, Mary E D; Leisenring, Wendy M; Martin, Paul J; Mendoza, Jason A; Reding, Kerryn W; Syrjala, Karen L; Lee, Stephanie J; Chow, Eric J

2018-04-01

The objective of this study was to evaluate whether modifiable cardiovascular risk conditions and lifestyle factors were temporally associated with an increased risk for ischemic heart disease and overall mortality in a cohort of hematopoietic cell transplantation (HCT) survivors. HCT recipients who had survived for ≥1 year, were ≥20 years old, and had undergone transplantation between 1970 and 2010 at a transplant referral center were surveyed in 2010-2011 about cardiovascular health and lifestyle factors (n = 3833). Respondents (n = 2360 [61.6%]) were followed to 2016 for incident ischemic heart disease and overall mortality. Among the 2360 transplant survivors (median age at the baseline survey, 55.9 years; median time since transplantation, 10.8 years), 162 (6.9%) reported ischemic heart disease at the baseline survey. Among those without ischemic heart disease at the baseline survey (n = 2198), the 5-year cumulative incidence of subsequent ischemic heart disease was 4.3%. Obesity, dyslipidemia, diabetes, and physical inactivity at baseline were associated with an increased risk for subsequent ischemic heart disease (hazard ratio [HRs] ≥ 1.8). Greater physical activity and fruit/vegetable intake at baseline were associated with subsequent lower overall mortality (HRs ≤ 0.7). When jointly considered, each additional cardiovascular risk condition and each adverse lifestyle factor were independently associated with subsequent ischemic heart disease (HR for risk conditions, 1.4; 95% confidence interval [CI], 1.0-1.9; HR for lifestyle factors, 1.9; 95% CI, 1.2-2.9), and adverse lifestyle factors remained associated with overall mortality (HR, 1.8; 95% CI, 1.5-2.3). These results support strong efforts to promote healthy lifestyle behaviors and to treat cardiovascular risk factors aggressively in HCT survivors. This may reduce future ischemic heart disease and overall mortality in this high-risk population. Cancer 2018;124:1507-15. © 2018 American Cancer Society. © 2018 American Cancer Society.

Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.

PubMed

Akinyemi, Rufus; Arnett, Donna K; Tiwari, Hemant K; Ovbiagele, Bruce; Sarfo, Fred; Srinivasasainagendra, Vinodh; Irvin, Marguerite Ryan; Adeoye, Abiodun; Perry, Rodney T; Akpalu, Albert; Jenkins, Carolyn; Owolabi, Lukman; Obiako, Reginald; Wahab, Kolawole; Sanya, Emmanuel; Komolafe, Morenikeji; Fawale, Michael; Adebayo, Philip; Osaigbovo, Godwin; Sunmonu, Taofiki; Olowoyo, Paul; Chukwuonye, Innocent; Obiabo, Yahaya; Akpa, Onoja; Melikam, Sylvia; Saulson, Raelle; Kalaria, Raj; Ogunniyi, Adesola; Owolabi, Mayowa

2017-08-15

Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin-6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men=198; Women=231) and stroke- free (N=483) controls (Men=236; Women=247). Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans=8.6%) was significantly associated with ischemic stroke in men (OR=2.006, 95% CI=[1.065, 3.777], p=0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans=1.7%) was also associated with ischemic stroke in men (OR=2.550, 95% CI=[1.027, 6.331], p=0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous monitoring of myocardial acid-base status during intermittent warm blood cardioplegia.

PubMed

Graffigna, A C L; Nollo, G; Pederzolli, C; Ferrari, P; Widesott, L; Antolini, R

2002-06-01

Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15-20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid-base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34-37 degrees C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO(2), PCO(2), pH, and temperature sensor (Paratrend7 (R), Philips Medical System) inserted into the coronary sinus. Mean cross-clamping time was 76+/-26 min; ischemic time was 13+/-0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28+/-0.14 during the first ischemic period, to 7.16+/-0.19 during the third ischemic period - P=0.003). PO(2) decreased rapidly at 90% in 5.0+/-1.2 min after every reperfusion. During ischemia, PCO(2) increased steadily at 1.6+/-0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42+/-12 mmHg during the first ischemic period, to 53+/-23 mmHg during the third ischemic period - P=0.05). Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.

CXCL12 Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain.

PubMed

Li, Yaning; Tang, Guanghui; Liu, Yanqun; He, Xiaosong; Huang, Jun; Lin, Xiaojie; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

2015-10-01

Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-α (PDGFRα)-positive and PDGFRα/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRα- and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. This study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In contrast to many experimental studies that provide treatment before ischemic insult, CXCL12 gene therapy was performed 1 week after brain ischemia, which significantly prolonged the therapeutic time window of brain ischemia. ©AlphaMed Press.

Effects of Donor Age and Cold Ischemia on Liver Transplantation Outcomes According to the Severity of Recipient Status.

PubMed

Grąt, Michał; Wronka, Karolina M; Patkowski, Waldemar; Stypułkowski, Jan; Grąt, Karolina; Krasnodębski, Maciej; Masior, Łukasz; Lewandowski, Zbigniew; Krawczyk, Marek

2016-02-01

BackgroundProlonged cold ischemic time (CIT) and increased donor age are well-known factors negatively influencing outcomes after liver transplantation (LT). The aim of this study was to evaluate whether the magnitude of their negative effects is related to recipient model for end-stage liver disease (MELD) score. This retrospective study was based on a cohort of 1402 LTs, divided into those performed in low-MELD (<10), moderate-MELD (10–20), and high-MELD (>20) recipients. While neither donor age (p = 0.775) nor CIT (p = 0.561) was a significant risk factor for worse 5-year graft survival in low-MELD recipients, both were found to yield independent effects (p = 0.003 and p = 0.012, respectively) in moderate-MELD recipients, and only CIT (p = 0.004) in high-MELD recipients. However, increased donor age only triggered the negative effect of CIT in moderate-MELD recipients, which was limited to grafts recovered from donors aged ≥46 years (p = 0.019). Notably, utilization of grafts from donors aged ≥46 years with CIT ≥9 h in moderate-MELD recipients (p = 0.003) and those with CIT ≥9 h irrespective of donor age in high-MELD recipients (p = 0.031) was associated with particularly compromised outcomes. In conclusion, the negative effects of prolonged CIT seem to be limited to patients with moderate MELD receiving organs procured from older donors and to high-MELD recipients, irrespective of donor age. Varying effects of donor age and CIT according to recipient MELD score should be considered during the allocation process in order to avoid high-risk matches.

Control of flowering time and cold response by a NAC-domain protein in Arabidopsis.

PubMed

Yoo, So Yeon; Kim, Yunhee; Kim, Soo Young; Lee, Jong Seob; Ahn, Ji Hoon

2007-07-25

Plants must integrate complex signals from environmental and endogenous cues to fine-tune the timing of flowering. Low temperature is one of the most common environmental stresses that affect flowering time; however, molecular mechanisms underlying the cold temperature regulation of flowering time are not fully understood. We report the identification of a novel regulator, LONG VEGETATIVE PHASE 1 (LOV1), that controls flowering time and cold response. An Arabidopsis mutant, longvegetative phase 1-1D (lov1-1D) showing the late-flowering phenotype, was isolated by activation tagging screening. Subsequent analyses demonstrated that the phenotype of the mutant resulted from the overexpression of a NAC-domain protein gene (At2g02450). Both gain- and loss-of-function alleles of LOV1 affected flowering time predominantly under long-day but not short-day conditions, suggesting that LOV1 may act within the photoperiod pathway. The expression of CONSTANS (CO), a floral promoter, was affected by LOV1 level, suggesting that LOV1 controls flowering time by negatively regulating CO expression. The epistatic relationship between CO and LOV1 was consistent with this proposed regulatory pathway. Physiological analyses to elucidate upstream signalling pathways revealed that LOV1 regulates the cold response in plants. Loss of LOV1 function resulted in hypersensitivity to cold temperature, whereas a gain-of-function allele conferred cold tolerance. The freezing tolerance was accompanied by upregulation of cold response genes, COLD-REGULATED 15A (COR15A) and COLD INDUCED 1 (KIN1) without affecting expression of the C-repeat-binding factor/dehydration responsive element-binding factor 1 (CBF/DREB1) family of genes. Our study shows that LOV1 functions as a floral repressor that negatively regulates CO expression under long-day conditions and acts as a common regulator of two intersecting pathways that regulate flowering time and the cold response, respectively. Our results suggest an overlapping pathway for controlling cold stress response and flowering time in plants.

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke.

PubMed

Lange, Kristin S; Nave, Alexander H; Liman, Thomas G; Grittner, Ulrike; Endres, Matthias; Ebinger, Martin

2017-01-01

The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1-4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19-196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9-194 days; P=0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19-5.67; P=0.016). Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger, multicenter trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378468. © 2016 American Heart Association, Inc.

Temporal Differences in MicroRNA Expression Patterns in Astrocytes and Neurons after Ischemic Injury

PubMed Central

Ziu, Mateo; Fletcher, Lauren; Rana, Shushan; Jimenez, David F.; Digicaylioglu, Murat

2011-01-01

MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that modulate gene translation. Their expression is altered in many central nervous system (CNS) injuries suggesting a role in the cellular response to stress. Current studies in brain tissue have not yet described the cell-specific temporal miRNA expression patterns following ischemic injury. In this study, we analyzed the expression alterations of a set of miRNAs in neurons and astrocytes subjected to 60 minutes of ischemia and collected at different time-points following this injury. To mimic ischemic conditions and reperfusion in vitro, cortical primary neuronal and astrocytic cultures prepared from fetal rats were first placed in oxygen and glucose deprived (OGD) medium for 60 minutes, followed by their transfer into normoxic pre-conditioned medium. Total RNA was extracted at different time-points after the termination of the ischemic insult and the expression levels of miRNAs were measured. In neurons exposed to OGD, expression of miR-29b was upregulated 2-fold within 6 h and up to 4-fold at 24 h post-OGD, whereas induction of miR-21 was upregulated 2-fold after 24 h when compared to expression in neurons under normoxic conditions. In contrast, in astrocytes, miR-29b and miR-21 were upregulated only after 12 h. MiR-30b, 107, and 137 showed expression alteration in astrocytes, but not in neurons. Furthermore, we show that expression of miR-29b was significantly decreased in neurons exposed to Insulin-Like Growth Factor I (IGF-I), a well documented neuroprotectant in ischemic models. Our study indicates that miRNAs expression is altered in neurons and astrocytes after ischemic injury. Furthermore, we found that following OGD, specific miRNAs have unique cell-specific temporal expression patterns in CNS. Therefore the specific role of each miRNA in different intracellular processes in ischemic brain and the relevance of their temporal and spatial expression patterns warrant further investigation that may lead to novel strategies for therapeutic interventions. PMID:21373187

Identification of ischemic regions in a rat model of stroke.

PubMed

Popp, Anke; Jaenisch, Nadine; Witte, Otto W; Frahm, Christiane

2009-01-01

Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study.

Identification of Ischemic Regions in a Rat Model of Stroke

PubMed Central

Popp, Anke; Jaenisch, Nadine; Witte, Otto W.; Frahm, Christiane

2009-01-01

Background Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. Methodology/Principal Findings Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. Conclusions/Significance TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study. PMID:19274095

Preconditioning, postconditioning and their application to clinical cardiology.

PubMed

Kloner, Robert A; Rezkalla, Shereif H

2006-05-01

Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing ischemia have been examined in numerous experimental studies. However, despite the effectiveness of ischemic preconditioning and preconditioning mimetics for protecting ischemic myocardium, there are no preconditioning-based therapies that are routinely used in clinical medicine at the current time. Part of the problem is the need to administer therapy prior to the known ischemic event. Other issues are that percutaneous coronary intervention technology has advanced so far (with the development of stents and drug-eluting stents) that ischemic preconditioning or preconditioning mimetics have not been needed in most interventional cases. Recent clinical trials such as AMISTAD I and II (Acute Myocardial Infarction STudy of ADenosine) suggest that some preconditioning mimetics may reduce myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known coronary artery disease. It is possible that some of the benefit described for adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon. It is probable that postconditioning--in which reperfusion is interrupted with brief coronary occlusions and reperfusion sequences--is more likely than preconditioning to be feasible as a clinical application to patients undergoing percutaneous coronary intervention for acute myocardial infarction.

Association Between Dehydration and Short-Term Risk of Ischemic Stroke in Patients with Atrial Fibrillation.

PubMed

Swerdel, Joel N; Janevic, Teresa M; Kostis, William J; Faiz, Ambarina; Cosgrove, Nora M; Kostis, John B

2017-04-01

Previous cross-sectional studies have demonstrated a higher incidence of dehydration in patients admitted for stroke suggesting a possible association. However, the temporality of the association has not been well established. We examined whether dehydration increases the risk of ischemic stroke in patients with a recent hospitalization for atrial fibrillation (AF). Data was from 1994 to 2012 from the Myocardial Infarction Data Acquisition System (MIDAS), a repository of in-patient records New Jersey hospitals, for AF hospitalizations (n = 1,282,787). Estimates for the association between AF hospitalization with/without dehydration and ischemic stroke within 30 days post-AF discharge were determined using log-linear multivariable modeling adjusting for socio-demographic factors and comorbid conditions. Within 10 days of discharge for AF, patients 18-80 years old (YO) with comorbid dehydration had a 60 % higher risk of ischemic stroke compared to AF patients without comorbid dehydration (adjusted risk ratio (ARR) 1.60, 95 % confidence interval (CI) 1.28-2.00). Eighteen- to 80-YO patients had a 34 % higher risk of ischemic stroke in days 11-20 post-AF discharge (ARR 1.34, 95 % CI 1.04, 1.74). There was no difference in the risk of stroke in 18-80-YO patients with or without prior dehydration during days 21-30 post-AF discharge. We also found no difference in the risk of ischemic stroke during any time period in patients over 80 YO. Dehydration may be a significant risk factor for ischemic stroke in patients 18-80 YO with AF.

Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis.

PubMed

Wang, Shi-Yu; Cui, Xin-Long; Xue, Fu-Shan; Duan, Ran; Li, Rui-Ping; Liu, Gao-Pu; Yang, Gui-Zhen; Sun, Chao

2016-05-01

Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model. One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group. This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

AMPA antagonist LY293558 does not affect the severity of hypoxic-ischemic injury in newborn pigs.

PubMed

LeBlanc, M H; Li, X Q; Huang, M; Patel, D M; Smith, E E

1995-10-01

LY293558 is a systemically active alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) excitatory amino acid antagonist. AMPA antagonists have shown promise in several adult hypoxic-ischemic brain injury models, and we wanted to see if this work could be extended to a newborn animal. Seventy-six (beta error < .10) 0- to 3-day-old piglets under 1.5% isoflurane anesthesia underwent placement of carotid snares and arterial and venous catheters. While paralyzed with succinylcholine under 0.5% isoflurane, 50% nitrous oxide, piglets were randomly assigned to receive either 5 mg/kg or 15 mg/kg of LY293558 or saline at time--10 minutes and again 10 hours later. At time 0, both carotid arteries were clamped, and blood was withdrawn to reduce the blood pressure to two thirds of normal. At time 15 minutes, inspired oxygen was reduced to 6%. At time 30 minutes, the carotid snares were released, the withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third day after the hypoxic-ischemic injury, the animals were killed by perfusion of the brain with 10% formalin. Brain pathology was scored by a blinded observer. There were no significant differences between the drug-treated and control groups. The systemically active AMPA antagonist LY293558, when given at a dose of 5 mg/kg or 15 mg/kg before injury and 10 hours later, does not affect the severity of hypoxic-ischemic brain injury in newborn piglets. Neither AMPA receptor activity nor NMDA receptor activity are important in brain injury in this model.

Inflammatory Disequilibrium in Stroke

PubMed Central

Petrovic-Djergovic, Danica; Goonewardena, Sascha N.; Pinsky, David J.

2016-01-01

Over the past several decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. Understanding the benefits of timely reperfusion has led to the development of thrombolytic therapy as the cornerstone of current management of ischemic stroke, but there remains much to be learned about mechanisms of neuronal ischemic and reperfusion injury and associated inflammation. For ischemic stroke, novel therapeutic targets have continued to remain elusive. When considering modern molecular biologic techniques, advanced translational stroke models, and clinical studies, a consistent pattern emerges, implicating perturbation of the immune equilibrium by stroke in both central nervous system injury and repair responses. Stroke triggers activation of the neuroimmune axis, comprised of multiple cellular constituents of the immune system resident within the parenchyma of the brain, leptomeninges, and vascular beds, as well as through secretion of biological response modifiers and recruitment of immune effector cells. This neuroimmune activation can directly impact the initiation, propagation, and resolution phases of ischemic brain injury. In order to leverage a potential opportunity to modulate local and systemic immune responses to favorably affect the stroke disease curve, it is necessary to expand our mechanistic understanding of the neuroimmune axis in ischemic stroke. This review explores the frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke. PMID:27340273

Premature ventricular complexes on screening electrocardiogram and risk of ischemic stroke.

PubMed

Agarwal, Sunil K; Chao, Jennifer; Peace, Frederick; Judd, Suzanne E; Kissela, Brett; Kleindorfer, Dawn; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2015-05-01

Premature ventricular complexes (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. This analysis included 24 460 participants (aged, 64.5+9.3 years; 55.1% women; 40.0% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. A total of 1415 (5.8%) participants had at least 1 PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a cox proportional hazards model adjusted for age, sex, race, geographic region, education, previous heart disease, systolic blood pressure, blood pressure-lowering medications, current smoking, diabetes mellitus, left ventricular hypertrophy by ECG, and aspirin use and warfarin use, the presence of PVCs was associated with 38% increased risk of ischemic stroke (hazard ratio [95% confidence interval], 1.38 [1.05-1.81]). PVCs are common on routine screening ECGs and are associated with an increased risk of ischemic stroke. © 2015 American Heart Association, Inc.

Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

PubMed Central

Yang, Hong; Zhao, Guang-Yue; Zhang, Geng; Lu, Zhi-Hong; Huang, Yan-Hong; Ma, Xiang-Dong; Liu, Hai-Xia; Liang, Sheng-Ru; Yang, Fang; Chen, Bi-Liang

2013-01-01

Objective To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. Methods In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. Results Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. Conclusion We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research. PMID:24278415

Methylene blue attenuates ischemia--reperfusion injury in lung transplantation.

PubMed

Abreu, Marcus da Matta; Pazetti, Rogerio; Almeida, Francine Maria de; Correia, Aristides Tadeu; Parra, Edwin Roger; Silva, Laís Pereira da; Vieira, Rodolfo de Paula; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

2014-12-01

Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. There was a significant decrease in exhaled nitric oxide, neutrophils, interleukin-6, and tumor necrosis factor-α in MB-treated animals. PaO2 and uric acid levels were higher in MB group. MB was able in attenuating IRI in this LTx model. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution of endovascular stroke therapies and devices.

PubMed

Wallace, Adam N; Kansagra, Akash P; McEachern, James; Moran, Christopher J; Cross, Dewitte T; Derdeyn, Colin P

2016-01-01

Acute ischemic stroke is caused by occlusion of a cerebral artery, resulting in loss of brain tissue and neurologic deficits. However, a portion of the ischemic brain can be salvaged if blood flow is restored within an appropriate time frame. The past year has seen the publication of five positive randomized controlled trials demonstrating substantial benefit of mechanical thrombectomy in select patients with large vessel cerebrovascular occlusion. This progress is related to several factors, but most importantly, dramatic improvements in speed and rates of recanalization with the latest generation devices. In this article, we review the evolution of endovascular acute ischemic stroke therapies and key design features of the most widely used devices.

Effects of topical oxygen therapy on ischemic wound healing.

PubMed

Rao, Congqiang; Xiao, Liling; Liu, Hongwei; Li, Shenghong; Lu, Jinqiang; Li, Jiangxuan; Gu, Shixing

2016-01-01

[Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing.

[The endoscopic and clinical features of Indigo Naturalis-associated ischemic lesions of colonic mucosa].

PubMed

Suo, Bao-jun; Zhou, Li-ya; Ding, Shi-gang; Lü, Yu-min; Gu, Fang; Lin, San-ren; Zheng, Ya-an

2011-08-01

By analysing the clinical features of Indigo Naturalis-associated ischemic lesion of colon mucosa to improve the precautionary and therapeutic level of the disease. Thirteen patients diagnosed as Indigo Naturalis-associated ischemic lesion of colon mucosa in Peking University Third Hospital from 2005 to 2010 were reviewed. The endoscopic and clinical features were analysed. The 13 patients with an average age of (60.6 ± 14.1) years old were prescribed Chinese traditional medicine containing Indigo Naturalis for psoriasis or idiopathic thrombocytopenic purpura (ITP). The ratio of males to females was 1:1.6. The typical manifestations were abdominal pain and bloody stool with watering diarrhea before bloody stool in 61.5% patients. Endoscopic and pathological characteristics were coincident with ischemic lesion and more like a chronic index. Vasodilatic medicine was effective and the average hemostatic time was (1.7 ± 0.8) days. The prognosis was well and no recurrence was found during 3 months follow-up. Patients having psoriasis or ITP treated with Chinese traditional medicine containing Indigo Naturalis have an inclination to colon mucosa lesions, even ischemic lesion. Careful assessment and observation before prescribing are necessary in these patients.

Recanalization Therapies in Acute Ischemic Stroke: Pharmacological Agents, Devices, and Combinations

PubMed Central

Sharma, Vijay K.; Teoh, Hock Luen; Wong, Lily Y. H.; Su, Jie; Ong, Benjamin K. C.; Chan, Bernard P. L.

2010-01-01

The primary aim of thrombolysis in acute ischemic stroke is recanalization of an occluded intracranial artery. Recanalization is an important predictor of stroke outcome as timely restoration of regional cerebral perfusion helps salvage threatened ischemic tissue. At present, intravenously administered tissue plasminogen activator (IV-TPA) remains the only FDA-approved therapeutic agent for the treatment of ischemic stroke within 3 hours of symptom onset. Recent studies have demonstrated safety as well as efficacy of IV-TPA even in an extended therapeutic window. However, the short therapeutic window, low rates of recanalization, and only modest benefits with IV-TPA have prompted a quest for alternative approaches to restore blood flow in an occluded artery in acute ischemic stroke. Although intra-arterial delivery of the thrombolytic agent seems effective, various logistic constraints limit its routine use and as yet no lytic agent have not received full regulatory approval for intra-arterial therapy. Mechanical devices and approaches can achieve higher rates of recanalization but their safety and efficacy still need to be established in larger clinical trials. The field of acute revascularization is rapidly evolving, and various combinations of pharmacologic agents, mechanical devices, and novel microbubble/ultrasound technologies are being tested in multiple clinical trials. PMID:20798838

Endovascular therapy for acute ischemic stroke.

PubMed

Broderick, Joseph P

2009-03-01

To review advances in endovascular therapy for acute ischemic stroke. Data from primate studies, randomized studies of intravenous recombinant tissue-type plasminogen activator, and nonrandomized and randomized studies of endovascular therapy were reviewed. Clinical trial data demonstrate the superiority of endovascular treatment with thrombolytic medication or mechanical methods to reopen arteries compared with control patients from the PROACT II Trial treated with heparin alone. However, these same clinical trials, as well as preclinical primate models, indicate that recanalization, whether by endovascular approaches or standard-dose recombinant tissue-type plasminogen activator, is unlikely to improve clinical outcome after a certain time point. Although the threshold beyond which reperfusion has no or little benefit has yet to be conclusively defined, accumulated data to this point indicate an overall threshold of approximately 6 to 7 hours. In addition, although the risk of symptomatic intracerebral hemorrhage is similar in trials of intravenous lytics and endovascular approaches, endovascular approaches have distinctive risk profiles that can impact outcome. The treatment of acute ischemic stroke is evolving with new tools to reopen arteries and salvage the ischemic brain. Ongoing randomized trials of these new approaches are prerequisite next steps to demonstrate whether reperfusion translates into clinical effectiveness. Physiologic time to reperfusion will remain critical no matter which tools prove most effective and safest.

Real-Time Visualization of Tissue Ischemia

NASA Technical Reports Server (NTRS)

Bearman, Gregory H. (Inventor); Chrien, Thomas D. (Inventor); Eastwood, Michael L. (Inventor)

2000-01-01

A real-time display of tissue ischemia which comprises three CCD video cameras, each with a narrow bandwidth filter at the correct wavelength is discussed. The cameras simultaneously view an area of tissue suspected of having ischemic areas through beamsplitters. The output from each camera is adjusted to give the correct signal intensity for combining with, the others into an image for display. If necessary a digital signal processor (DSP) can implement algorithms for image enhancement prior to display. Current DSP engines are fast enough to give real-time display. Measurement at three, wavelengths, combined into a real-time Red-Green-Blue (RGB) video display with a digital signal processing (DSP) board to implement image algorithms, provides direct visualization of ischemic areas.

Time-Resolved C-Arm Computed Tomographic Angiography Derived From Computed Tomographic Perfusion Acquisition: New Capability for One-Stop-Shop Acute Ischemic Stroke Treatment in the Angiosuite.

PubMed

Yang, Pengfei; Niu, Kai; Wu, Yijing; Struffert, Tobias; Dorfler, Arnd; Schafer, Sebastian; Royalty, Kevin; Strother, Charles; Chen, Guang-Hong

2015-12-01

Multimodal imaging using cone beam C-arm computed tomography (CT) may shorten the delay from ictus to revascularization for acute ischemic stroke patients with a large vessel occlusion. Largely because of limited temporal resolution, reconstruction of time-resolved CT angiography (CTA) from these systems has not yielded satisfactory results. We evaluated the image quality and diagnostic value of time-resolved C-arm CTA reconstructed using novel image processing algorithms. Studies were done under an Institutional Review Board approved protocol. Postprocessing of data from 21 C-arm CT dynamic perfusion acquisitions from 17 patients with acute ischemic stroke were done to derive time-resolved C-arm CTA images. Two observers independently evaluated image quality and diagnostic content for each case. ICC and receiver-operating characteristic analysis were performed to evaluate interobserver agreement and diagnostic value of this novel imaging modality. Time-resolved C-arm CTA images were successfully generated from 20 data sets (95.2%, 20/21). Two observers agreed well that the image quality for large cerebral arteries was good but was more limited for small cerebral arteries (distal to M1, A1, and P1). receiver-operating characteristic curves demonstrated excellent diagnostic value for detecting large vessel occlusions (area under the curve=0.987-1). Time-resolved CTAs derived from C-arm CT perfusion acquisitions provide high quality images that allowed accurate diagnosis of large vessel occlusions. Although image quality of smaller arteries in this study was not optimal ongoing modifications of the postprocessing algorithm will likely remove this limitation. Adding time-resolved C-arm CTAs to the capabilities of the angiography suite further enhances its suitability as a one-stop shop for care for patients with acute ischemic stroke. © 2015 American Heart Association, Inc.

Alteration of mean platelet volume in the pathogenesis of acute ischemic stroke: cause or consequence?

PubMed

Ayas, Zeynep Özözen; Can, Ufuk

2018-01-30

Platelets have a crucial role on vascular disease which are involved in pathogenesis of ischemic stroke. Platelet size is measured as mean platelet volume (MPV) and is a marker of platelet activity. Platelets contain more dense granules as the size increases and produce more serotonin and tromboglobulin (b-TG) than small platelets. In this study, the alteration of MPV values were investigated in patients with acute stroke, who had MPV values before stroke, during acute ischemic stroke and 7 days after the stroke. The relationship between this alteration and risk factors, etiology and localization of ischemic stroke were also investigated. Sixty-seven patients with clinically and radiologically established diagnoses of ischemic stroke were enrolled into the study and stroke etiology was classified by modified Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification and, modified Bamford classification was used for localization and stroke risk factors were also evaluated. The platelet counts and MPV values from patient files in patients who had values before stroke (at examination for another diseases), within 24 hours of symptom onset and after 7 further days were analysed. MPV values increased after stroke (10.59±2.26) compared with acute stroke values (9.84±1.64) and the values before stroke (9.59±1.72) (p<0.0001); this alteration of MPV values occured 7 days after stroke (p<0.016). There was a positive correlation between age and MPV values during acute stroke (r=0.270; p<0.05). Patients with atrial fibrillation had higher alteration in the time of MPV compared with patients without atrial fibrillation (p>0.006). We assessed for gender, men (n=38) had a higher alteration in the time of MPV compared with women (n=29) (p=0.013). Although there was no alteration of platelet counts, MPV values were increased 7 days after stroke in patients with acute ischemic stroke.

Short-term exposures to ambient air pollution and risk of recurrent ischemic stroke.

PubMed

Wing, Jeffrey J; Adar, Sara D; Sánchez, Brisa N; Morgenstern, Lewis B; Smith, Melinda A; Lisabeth, Lynda D

2017-01-01

To investigate the association between short-term changes in ambient pollution (particulate matter <2.5µm in aerodynamic diameter (PM 2.5 ) and ozone (O 3 )) and the risk of recurrent ischemic stroke among individuals living in a bi-ethnic community. We identified recurrent ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Associations between PM 2.5 (mean 24-h) and O 3 (maximal 8-h) levels, measured on the previous day, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. There were 317 recurrent ischemic strokes after excluding 41 strokes that occurred on days with missing air pollution data. Mean age was 72 years (SD=12) and median time to stroke recurrence was 1.1 years (IQR: 0.2-2.8 years). Median levels of PM 2.5 and O 3 over the study period were 7.7μg/m 3 (IQR: 5.6-10.7μg/m 3 ) and 35.2 ppb (IQR: 25.0-46.1 ppb), respectively. We observed no associations between previous-day PM 2.5 and O 3 and odds of recurrent stroke (OR=0.95 per 10µg/m 3 of PM 2.5 , 95% CI: 0.71-1.28 and OR=0.97 per 10ppb of O 3 , 95% CI: 0.87-1.07) after adjusting for ambient temperature and relative humidity. Co-adjustment of both pollutants did not change the results. We found no evidence of associations between previous-day air pollution levels and recurrent ischemic stroke. Research on the influence of air pollutants on risk of stroke recurrence is still in its infancy, and more research is necessary in studies that are adequately powered to understand the relation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

PubMed

Dai, Zhenyu; Chen, Fei; Yao, Lizheng; Dong, Congsong; Liu, Yang; Shi, Haicun; Zhang, Zhiping; Yang, Naizhong; Zhang, Mingsheng; Dai, Yinggui

2015-08-18

To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually decreased from hyper-acute to sub-acute cerebral infarction (P<0.05), but there were no difference of the relative VRA value between acute and sub-acute cerebral infarction. The relative DCavg value of infarction lesion to contra in hyper-acute infarction than that in acute and sub-acute infarction (P<0.05), however there was also no difference between acute and sub-acute infarction. ROC curve showed the best diagnosis cut off value of relative FA, VRA and DCavg of infarction lesions to contra were 0.852, 0.886 and 0.541 between hyper-acute and acute cerebral infarction, the best diagnosis cut off value of relative FA was 0.595 between acute and sub-acute cerebral infarction, respectively. The FA, VRA, DCavg and Exat value have specific change mode in acute ischemic cerebral infarction of different infarction time phases, which can be combine used in judging infarction time phase of acute ischemic cerebral infarction without clear onset time, thus to help selecting the reasonable treatment protocols.

The impacts of repeated cold exposure on insects.

PubMed

Marshall, Katie E; Sinclair, Brent J

2012-05-15

Insects experience repeated cold exposure (RCE) on multiple time scales in natural environments, yet the majority of studies of the effects of cold on insects involve only a single exposure. Three broad groups of experimental designs have been employed to examine the effects of RCE on insect physiology and fitness, defined by the control treatments: 'RCE vs cold', which compares RCE with constant cold conditions; 'RCE vs warm', which compares RCE with constant warm conditions; and 'RCE vs matched cold' which compares RCE with a prolonged period of cold matched by time to the RCE condition. RCE are generally beneficial to immediate survival, and increase cold hardiness relative to insects receiving a single prolonged cold exposure. However, the effects of RCE depend on the study design, and RCE vs warm studies cannot differentiate between the effects of cold exposure in general vs RCE in particular. Recent studies of gene transcription, immune function, feeding and reproductive output show that the responses of insects to RCE are distinct from the responses to single cold exposures. We suggest that future research should attempt to elucidate the mechanistic link between physiological responses and fitness parameters. We also recommend that future RCE experiments match the time spent at the stressful low temperature in all experimental groups, include age controls where appropriate, incorporate a pilot study to determine time and intensity of exposure, and measure sub-lethal impacts on fitness.

The Eurotransplant Study on Twin Lung Transplants (ESOTWIN): 90 paired single-lung transplants from the same donor.

PubMed

Smits, Jacqueline M A; Melman, Sonja; Mertens, Bart J A; Laufer, Gunther; Persijn, Guido G; Van Raemdonck, Dirk

2003-12-15

Despite its reduced benefit for a single recipient, the transplantation of two single-lung allografts as opposed to one bilateral lung transplant has the indisputable advantage of maximizing the number of patients that benefit from a single donor. In the period 1997 to 1999, 90 paired single-lung transplants (SLTx) from 45 donors were performed in 16 lung centers in Eurotransplant, with a complete follow-up of 1 year. No significant differences between left- and right-lung allograft recipients were observed regarding age, sex, primary disease, number of human leukocyte antigen mismatches, cold ischemic time, and donor-to-recipient cytomegalovirus match. Early posttransplant outcome, as assessed by oxygenation index at 12, 24, and 48 hr, also did not differ significantly, and there were no differences in time to extubation and time spent in the intensive care unit. In the first month, six left- and three right-lung allograft recipients died. Bronchiolitis obliterans syndrome developed in 5 of 39 left-lung and 10 of 42 right-lung allograft recipients. If the retrieval team was different from the transplanting team, a significantly worse 1-year posttransplant survival rate was seen in patients who underwent left SLTx compared with those who underwent right SLTx (62% vs. 92%, respectively; P=0.04). More fatal posttransplant complications occur in patients undergoing left SLTx compared with right SLTx. A less optimistic assessment of the left lung by the not-implanting retrieval team is warranted.

Factors affecting outdoor exposure in winter: population-based study

NASA Astrophysics Data System (ADS)

Mäkinen, Tiina M.; Raatikka, Veli-Pekka; Rytkönen, Mika; Jokelainen, Jari; Rintamäki, Hannu; Ruuhela, Reija; Näyhä, Simo; Hassi, Juhani

2006-09-01

The extent of outdoor exposure during winter and factors affecting it were examined in a cross-sectional population study in Finland. Men and women aged 25-74 years from the National FINRISK 2002 sub-study ( n=6,591) were queried about their average weekly occupational, leisure-time and total cold exposure during the past winter. The effects of gender, age, area of residence, occupation, ambient temperature, self-rated health, physical activity and education on cold exposure were analysed. The self-reported median total cold exposure time was 7 h/week (8 h men, 6 h women),<1 h/week (2 h men, 0 h women) at work, 4 h/week (5 h men, 4 h women) during leisure time and 1 h/week (1 h men, 1.5 h women) while commuting to work. Factors associated with increased occupational cold exposure among men were: being employed in agriculture, forestry and industry/mining/construction or related occupations, being less educated and being aged 55-64 years. Factors associated with increased leisure-time cold exposure among men were: employment in industry/mining/construction or related occupations, being a pensioner or unemployed, reporting at least average health, being physically active and having college or vocational education. Among women, being a housewife, pensioner or unemployed and engaged in physical activity increased leisure-time cold exposure, and young women were more exposed than older ones. Self-rated health was positively associated with leisure time cold exposure in men and only to a minor extent in women. In conclusion, the subjects reported spending 4% of their total time under cold exposure, most of it (71%) during leisure time. Both occupational and leisure-time cold exposure is greater among men than women.

Prevalence of cold sensitivity in patients with hand pathology.

PubMed

Novak, Christine B; McCabe, Steven J

2015-06-01

The purpose of this study was to evaluate the prevalence of cold sensitivity in patients with hand- and wrist-related diagnoses. We included English-speaking adults who were more than 1 month following hand injury or onset of symptoms. Patients were asked if exposure to cold air or water provoked cold-related symptoms and to rank symptom severity (scale 0-10). Statistical analyses evaluated the relationships between the cold sensitivity and independent variables (age, gender, history of trauma, and time from injury/symptoms). There were 197 patients (mean age 49 ± 16 years): 98 trauma and 99 non-trauma cases. Cold-induced symptoms were reported by 34 %, with 10 % reporting severe symptoms. Exposure to cold air is the most common catalyst; mean severity score was 6.7 ± 2.2. Those with traumatic injuries compared to non-trauma diagnoses reported significantly more cold-induced symptoms (p = .04). Using backward linear regression, the significant predictors of cold symptom severity were trauma (p = .004) and time since onset (p = .003). Including only the trauma patients in the regression model, the significant predictor was time since injury (p = .005). Cold-induced symptoms are reported by more than 30 % of hand-related diagnoses, and exposure to cold air was the most commonly reported trigger. The significant predictors of cold-induced symptoms are traumatic injuries and longer time from injury. This study provides evidence of the common problem of cold sensitivity in patients with hand pathology. Prognostic Level II.

Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation.

PubMed

Mergental, H; Perera, M T P R; Laing, R W; Muiesan, P; Isaac, J R; Smith, A; Stephenson, B T F; Cilliers, H; Neil, D A H; Hübscher, S G; Afford, S C; Mirza, D F

2016-11-01

The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT. © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

[Renal failure in surgery of abdominal aorta aneurysms].

PubMed

Pokrovskiĭ, A V; Asamov, R E; Ermoliuk, R S; Iudin, V I; Kapanadze, G I

1994-09-01

The authors analyse the experience in operations for resection of an aneurysm of the abdominal aorta in 70 patients, which were performed at the Vishnevsky Institute of Surgery, AMS of Russia, from 1983 to 1991. Preoperative examination revealed renal insufficiency in 8 (11.4%) patients. Resection of the aneurysm of the abdominal aorta with one-stage prosthetics of the renal arteries was carried out in 10 cases. To prevent ischemic damage to the renal parenchyma and acute renal insufficiency, local methods of kidney protection (isolated cold perfusion--2 and normothermic aorto-renal perfusion--2) were applied in 4 of 70 cases. The work discusses the methods of kidney protection and the indications and contraindications for their use, and factors promoting the development of postoperative renal insufficiency. Postoperative complications are shown and their causes are identified.

Cold resistance depends on acclimation and behavioral caste in a temperate ant

NASA Astrophysics Data System (ADS)

Modlmeier, Andreas P.; Pamminger, Tobias; Foitzik, Susanne; Scharf, Inon

2012-10-01

Adjusting to low temperatures is important for animals living in cold environments. We studied the chill-coma recovery time in temperate ant workers ( Temnothorax nylanderi) from colonies collected in autumn and spring in Germany. We experimentally acclimated these ant colonies to cold temperatures followed by warm temperatures. As expected, cold-acclimated workers recovered faster from freezing temperatures, but subsequent heat acclimation did not change the short recovery times observed after cold acclimation. Hence, either heat acclimation improves cold tolerance, possibly as a general response to stress, or at least it does not negate enhanced cold tolerance following cold acclimation. Colonies collected in spring showed similar cold tolerance levels to cold-acclimated colonies in the laboratory. Next, we compared the chill-coma recovery time of different worker castes and found that exterior workers recovered faster than interior workers. This difference may be related to their more frequent exposure to cold, higher activity level, or distinct physiology. Interior workers were also heavier and showed a higher gaster-to-head ratio and thorax ratio compared to exterior workers. An obvious difference between exterior and interior workers is activity level, but we found no link between activity and cold tolerance. This suggests that physiology rather than behavioral differences could cause the increased cold tolerance of exterior workers. Our study reveals the importance of acclimation for cold tolerance under natural and standardized conditions and demonstrates differences in cold tolerance and body dimensions in monomorphic behavioral castes of an ant.

A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

PubMed

Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K

2014-01-01

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. © 2014 by the Wound Healing Society.

Physical activity and risk of ischemic stroke in the Northern Manhattan Study

PubMed Central

Willey, J Z.; Moon, Y P.; Paik, M C.; Boden-Albala, B; Sacco, R L.; Elkind, M S.V.

2009-01-01

Background: It is controversial whether physical activity is protective against first stroke among older persons. We sought to examine whether physical activity, as measured by intensity of exercise and energy expended, is protective against ischemic stroke. Methods: The Northern Manhattan Study is a prospective cohort study in older, urban-dwelling, multiethnic, stroke-free individuals. Baseline measures of leisure-time physical activity were collected via in-person questionnaires. Cox proportional hazards models were constructed to examine whether energy expended and intensity of physical activity were associated with the risk of incident ischemic stroke. Results: Physical inactivity was present in 40.5% of the cohort. Over a median follow-up of 9.1 years, there were 238 incident ischemic strokes. Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65, 95% confidence interval [0.44–0.98]). Engaging in any physical activity vs none (adjusted HR 1.16, 95% CI 0.88–1.51) and energy expended in kcal/wk (adjusted HR per 500-unit increase 1.01, 95% CI 0.99–1.03) were not associated with ischemic stroke risk. There was an interaction of sex with intensity of physical activity (p = 0.04), such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR 0.37, 95% CI 0.18–0.78), but not in women (adjusted HR 0.92, 95% CI 0.57–1.50). Conclusions: Moderate- to heavy-intensity physical activity, but not energy expended, is protective against risk of ischemic stroke independent of other stroke risk factors in men in our cohort. Engaging in moderate to heavy physical activities may be an important component of primary prevention strategies aimed at reducing stroke risk. GLOSSARY CI = confidence interval; HR = hazard ratio; MET = metabolic equivalents. PMID:19933979

3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

PubMed

Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

2017-05-01

Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

Tricuspid Regurgitation Associated With Ischemic Mitral Regurgitation: Characterization, Evolution After Mitral Surgery, and Value of Tricuspid Repair.

PubMed

Navia, José L; Elgharably, Haytham; Javadikasgari, Hoda; Ibrahim, Ahmed; Koprivanac, Marijan; Lowry, Ashley M; Blackstone, Eugene H; Klein, Allan L; Gillinov, A Marc; Roselli, Eric E; Svensson, Lars G

2017-08-01

Tricuspid regurgitation (TR) often accompanies ischemic mitral regurgitation and is generally assumed to be a secondary consequence of altered hemodynamics of the left-sided regurgitation. We hypothesized that it may also be a direct consequence of right-sided ischemic disease. Therefore, our objectives were to (1) characterize the nature of this TR and (2) describe its time course after mitral valve surgery for ischemic mitral regurgitation, with or without concomitant tricuspid valve repair. From 2001 to 2011, 568 patients with ischemic mitral regurgitation underwent mitral valve surgery. They had varying degrees of TR and altered right-side heart morphology and function; 131 had concomitant tricuspid valve repair. Postoperatively, 1,395 echocardiograms were available to assess residual and recurrent TR. Greater severity of preoperative TR was accompanied by larger tricuspid valve diameter, greater leaflet tethering, worse right ventricular function, and higher right ventricular pressure (all p [trend] ≤ 0.002). Without tricuspid valve repair, 31% of patients with no preoperative TR had moderate or greater TR by 5 years, as did 62% with moderate TR. With tricuspid valve repair, 25% with moderate preoperative TR remained in that grade at 5 years, but 11% had severe TR. Tricuspid regurgitation accompanying ischemic mitral regurgitation is associated with right-side heart remodeling and dysfunction often mirroring that occurring in the left side of the heart-ischemic TR. Tricuspid valve repair is effective initially, but as with mitral valve repair, TR progressively returns. Therefore, when the severity of TR and right-sided remodeling reaches the point of irreversibility, it may be an indication to eliminate the TR by replacing the tricuspid valve. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A Framework for Image-Based Modeling of Acute Myocardial Ischemia Using Intramurally Recorded Extracellular Potentials.

PubMed

Burton, Brett M; Aras, Kedar K; Good, Wilson W; Tate, Jess D; Zenger, Brian; MacLeod, Rob S

2018-05-21

The biophysical basis for electrocardiographic evaluation of myocardial ischemia stems from the notion that ischemic tissues develop, with relative uniformity, along the endocardial aspects of the heart. These injured regions of subendocardial tissue give rise to intramural currents that lead to ST segment deflections within electrocardiogram (ECG) recordings. The concept of subendocardial ischemic regions is often used in clinical practice, providing a simple and intuitive description of ischemic injury; however, such a model grossly oversimplifies the presentation of ischemic disease-inadvertently leading to errors in ECG-based diagnoses. Furthermore, recent experimental studies have brought into question the subendocardial ischemia paradigm suggesting instead a more distributed pattern of tissue injury. These findings come from experiments and so have both the impact and the limitations of measurements from living organisms. Computer models have often been employed to overcome the constraints of experimental approaches and have a robust history in cardiac simulation. To this end, we have developed a computational simulation framework aimed at elucidating the effects of ischemia on measurable cardiac potentials. To validate our framework, we simulated, visualized, and analyzed 226 experimentally derived acute myocardial ischemic events. Simulation outcomes agreed both qualitatively (feature comparison) and quantitatively (correlation, average error, and significance) with experimentally obtained epicardial measurements, particularly under conditions of elevated ischemic stress. Our simulation framework introduces a novel approach to incorporating subject-specific, geometric models and experimental results that are highly resolved in space and time into computational models. We propose this framework as a means to advance the understanding of the underlying mechanisms of ischemic disease while simultaneously putting in place the computational infrastructure necessary to study and improve ischemia models aimed at reducing diagnostic errors in the clinic.

Time course and prognostic value of plasma levels of N-terminal pro-brain natriuretic peptide in patients after ischemic stroke.

PubMed

Yip, Hon-Kan; Sun, Cheuk-Kwan; Chang, Li-Teh; Chen, Mien-Cheng; Liou, Chia-Wei

2006-04-01

The association between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognostic outcomes in patients after ischemic stroke remains unknown. The present study tested the hypothesis that NT-proBNP level is noticeably increased after ischemic stroke and that elevated NT-proBNP is associated with unfavorable clinical outcomes (UFCO). Blood samples for NT-proBNP levels were collected serially and examined with sandwich immunoassay after acute ischemic stroke in 86 consecutive patients. The NT-proBNP levels were also measured in 30 healthy control volunteers and 30 at-risk control subjects. The NT-proBNP levels were significantly higher at 4 intervals after ischemic stroke than in healthy and at-risk control subjects (all p<0.001). The NT-proBNP decreased to a significantly lower level on day 21 and to a substantially lower level on day 90. Additionally, the NT-proBNP level at any of the 4 intervals was significantly higher in patients with than in patients without UFCO (defined as combined congestive heart failure > or = class 3, acute myocardial infarction, recurrent stroke or any cause of death) (all p<0.01). Multivariate analysis demonstrated that age and NIH Stroke Scale were the 2 strongest independent predictors of increased NT-proBNP levels (all p<0.01). Furthermore, increased NT-proBNP (> or = 150 pg/ml) was the strongest independent predictor of long-term (mean follow-up: 24 months) UFCO (26 patients) (all p<0.05). The NT-proBNP level was markedly elevated after acute ischemic stroke and declined substantially thereafter. An increased NT-proBNP level was strongly and independently correlated with UFCO in patients after ischemic stroke.

Normal tubular regeneration and differentiation of the post-ischemic kidney in mice lacking vimentin.

PubMed Central

Terzi, F.; Maunoury, R.; Colucci-Guyon, E.; Babinet, C.; Federici, P.; Briand, P.; Friedlander, G.

1997-01-01

Proliferation and dedifferentiation of tubular cells are the hallmark of early regeneration after renal ischemic injury. Vimentin, a class III intermediate filament expressed only in mesenchymal cells of mature mammals, was shown to be transiently expressed in post-ischemic renal tubular epithelial cells. Vimentin re-expression was interpreted as a marker of cellular dedifferentiation, but its role in tubular regeneration after renal ischemia has also been hypothesized. This role was evaluated in mice bearing a null mutation of the vimentin gene. Expression of vimentin, proliferating cell nuclear antigen (a marker of cellular proliferation), and villin (a marker of differentiated brush-border membranes) was studied in wild-type (Vim+/+), heterozygous (Vim+/-), and homozygous (Vim-/-) mice subjected to transient ischemia of the left kidney. As expected, vimentin was detected by immunohistochemistry at the basal pole of proximal tubular cells from post-ischemic kidney in Vim+/+ and Vim+/- mice from day 2 to day 28. The expression of the reporter gene beta-galactosidase in Vim+/- and Vim-/- mice confirmed the tubular origin of vimentin. No compensatory expression of keratin could be demonstrated in Vim-/- mice. The intensity of proliferating cell nuclear antigen labeling and the pattern of villin expression were comparable in Vim-/-, Vim+/- and Vim+/+ mice at any time of the study. After 60 days, the structure of post-ischemic kidneys in Vim-/- mice was indistinguishable from that of normal non-operated kidneys in Vim+/+ mice. In conclusion, 1) the pattern of post-ischemic proximal tubular cell proliferation, differentiation, and tubular organization was not impaired in mice lacking vimentin and 2) these results suggest that the transient tubular expression of vimentin is not instrumental in tubular regeneration after renal ischemic injury. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 PMID:9094992

Lipid Profile Components and Risk of Ischemic Stroke

PubMed Central

Willey, Joshua Z.; Xu, Qiang; Boden-Albala, Bernadette; Paik, Myunghee C.; Moon, Yeseon Park; Sacco, Ralph L.; Elkind, Mitchell S. V.

2010-01-01

Objective To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. Design Population-based prospective cohort study. Setting Northern Manhattan, New York. Patients Stroke-free community residents. Intervention As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. Main Outcome Measures Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. Results After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53–9.51). Conclusions Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of stroke risk. PMID:19901173

Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry

PubMed Central

Wang, Wei Zhong

2008-01-01

Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery. PMID:18946882

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

PubMed

Mazighi, Mikael; Meseguer, Elena; Labreuche, Julien; Serfaty, Jean-Michel; Laissy, Jean-Pierre; Lavallée, Philippa C; Cabrejo, Lucie; Guidoux, Céline; Lapergue, Bertrand; Klein, Isabelle F; Olivot, Jean-Marc; Rouchaud, Aymeric; Desilles, Jean-Philippe; Schouman-Claeys, Elisabeth; Amarenco, Pierre

2012-11-01

Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours. DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024). DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With Stroke.

PubMed

Nogueira, Raul G; Silva, Gisele S; Lima, Fabricio O; Yeh, Yu-Chih; Fleming, Carol; Branco, Daniel; Yancey, Arthur H; Ratcliff, Jonathan J; Wages, Robert Keith; Doss, Earnest; Bouslama, Mehdi; Grossberg, Jonathan A; Haussen, Diogo C; Sakano, Teppei; Frankel, Michael R

2017-05-01

The Emergency Medical Services field triage to stroke centers has gained considerable complexity with the recent demonstration of clinical benefit of endovascular treatment for acute ischemic stroke. We sought to describe a new smartphone freeware application designed to assist Emergency Medical Services professionals with the field assessment and destination triage of patients with acute ischemic stroke. Review of the application's platform and its development as well as the different variables, assessments, algorithms, and assumptions involved. The FAST-ED (Field Assessment Stroke Triage for Emergency Destination) application is based on a built-in automated decision-making algorithm that relies on (1) a brief series of questions assessing patient's age, anticoagulant usage, time last known normal, motor weakness, gaze deviation, aphasia, and hemineglect; (2) a database of all regional stroke centers according to their capability to provide endovascular treatment; and (3) Global Positioning System technology with real-time traffic information to compute the patient's eligibility for intravenous tissue-type plasminogen activator or endovascular treatment as well as the distances/transportation times to the different neighboring stroke centers in order to assist Emergency Medical Services professionals with the decision about the most suitable destination for any given patient with acute ischemic stroke. The FAST-ED smartphone application has great potential to improve the triage of patients with acute ischemic stroke, as it seems capable to optimize resources, reduce hospital arrivals times, and maximize the use of both intravenous tissue-type plasminogen activator and endovascular treatment ultimately leading to better clinical outcomes. Future field studies are needed to properly evaluate the impact of this tool in stroke outcomes and resource utilization. © 2017 American Heart Association, Inc.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

PubMed

Cortijo, E; García-Bermejo, P; Calleja, A I; Pérez-Fernández, S; Gómez, R; del Monte, J M; Reyes, J; Arenillas, J F

2014-03-01

Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implementation of a clinical pathway based on a computerized physician order entry system for ischemic stroke attenuates off-hour and weekend effects in the ED.

PubMed

Yang, Jong Min; Park, Yoo Seok; Chung, Sung Phil; Chung, Hyun Soo; Lee, Hye Sun; You, Je Sung; Lee, Shin Ho; Park, Incheol

2014-08-01

Admission on weekends and off-hours has been associated with poor outcomes and mortality from acute stroke. The purpose of this study was to investigate whether an organized clinical pathway (CP) for ischemic stroke can effectively reduce the time from arrival to evaluation and treatment in the emergency department (ED) and improve outcomes, regardless of the time from arrival in the ED. We conducted a retrospective analysis of all consecutive patients included in the prospective registry database in the Brain Salvage through Emergency Stroke Therapy program, which uses the computerized physician order entry (CPOE) system. Patients were classified based on their time of arrival in the ED: group 1, normal working hours on weekdays; group 2, off-hours on weekdays; group 3, normal working hours on weekends; and group 4, off-hours on weekends. Clinical outcomes were categorized according to 30 days in-hospital mortality, in-hospital mortality, and the modified Rankin score during a single length of stay (LOS). No time intervals differed significantly among the 4 patient groups who received intravenous administration of tissue plasminogen activator (IV-tPA). Use of IV-tPA (P = .5110) was not affected by arrival in the ED on off-days or weekends. The overall mortality rate was 3.9%, and the median LOS was 7 days (Interquartile range (IQR), 5-10). By Kaplan-Meier analysis, the cumulative probability of mortality and survival did not differ significantly among the 4 groups over 30 days (P = .1557). An organized CP, based on CPOE, for ischemic stroke can effectively attenuate disparities in the time interval between ED arrival to evaluation and treatment regardless of ED arrival time. This pathway may also help to eliminate off-hour and weekend effects on outcomes from ischemic stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

National Institutes of Health Stroke Scale-Time Score Predicts Outcome after Endovascular Therapy in Acute Ischemic Stroke: A Retrospective Single-Center Study.

PubMed

Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Kohara, Nobuo

2016-05-01

Outcomes after successful endovascular therapy in acute ischemic stroke are associated with onset-to-reperfusion time (ORT) and the National Institutes of Health Stroke Scale (NIHSS) score. In intravenous recombinant tissue plasminogen activator therapy, the NIHSS-time score, calculated by multiplying onset-to-treatment time with the NIHSS score, has been shown to predict clinical outcomes. In this study, we assessed whether a similar combination of the ORT and the NIHSS score can be applied to predict the outcomes after endovascular therapy. We retrospectively reviewed the charts of 128 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy. We analyzed the association of the ORT, the NIHSS score, and the NIHSS-time score with good outcome (modified Rankin Scale score ≤ 2 at 3 months). Good outcome rates for patients with NIHSS-time scores of 84.7 or lower, scores higher than 84.7 up to 127.5 or lower, and scores higher than 127.5 were 72.1%, 44.2%, and 14.3%, respectively (P < .01). Multivariate logistic regression analysis revealed that the NIHSS-time score was an independent predictor of good outcomes (odds ratio, .372; 95% confidence interval, .175-.789) after adjusting for age, sex, internal carotid artery occlusion, plasma glucose level, ORT, and NIHSS score. The NIHSS-time score can predict good clinical outcomes after endovascular treatment. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cold adaptation shapes the robustness of metabolic networks in Drosophila melanogaster

PubMed Central

Williams, CM; Watanabe, M; Guarracino, MR; Ferraro, MB; Edison, AS; Morgan, TJ; Boroujerdi, AFB; Hahn, DA

2015-01-01

When ectotherms are exposed to low temperatures, they enter a cold-induced coma (chill coma) that prevents resource acquisition, mating, oviposition, and escape from predation. There is substantial variation in time taken to recover from chill coma both within and among species, and this variation is correlated with habitat temperatures such that insects from cold environments recover more quickly. This suggests an adaptive response, but the mechanisms underlying variation in recovery times are unknown, making it difficult to decisively test adaptive hypotheses. We use replicated lines of Drosophila melanogaster selected in the laboratory for fast (hardy) or slow (susceptible) chill-coma recovery times to investigate modifications to metabolic profiles associated with cold adaptation. We measured metabolite concentrations of flies before, during, and after cold exposure using NMR spectroscopy to test the hypotheses that hardy flies maintain metabolic homeostasis better during cold exposure and recovery, and that their metabolic networks are more robust to cold-induced perturbations. The metabolites of cold-hardy flies were less cold responsive and their metabolic networks during cold exposure were more robust, supporting our hypotheses. Metabolites involved in membrane lipid synthesis, tryptophan metabolism, oxidative stress, energy balance, and proline metabolism were altered by selection on cold tolerance. We discuss the potential significance of these alterations. PMID:25308124

Validation of Diagnoses of Transient Ischemic Attack in the Swedish Stroke Register (Riksstroke) TIA-Module.

PubMed

Buchwald, Fredrik; Ström, Jakob O; Norrving, Bo; Petersson, Jesper

2015-01-01

In 2010, the Swedish Stroke Register (Riksstroke; RS) established a module for transient ischemic attacks (RS-TIA). We report a diagnostic validation study of patients included in RS-TIA. During the first year, 7,825 patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA definition was applied. A sample of 180 patients (30 patients each from 6 hospitals), with a similar distribution of age and sex as in RS-TIA, was prepared. Two independent observers assessed medical records for quality of documentation and assigned a diagnosis of likely, possible, unlikely TIA or ischemic stroke, according to prespecified criteria. The 2 observers agreed in 77% of cases that the event was a likely or possible TIA, in 3% that the event was an ischemic stroke, and in 2% that the event was an unlikely TIA. The observers disagreed in 8% of patients on TIA vs. ischemic stroke, and in 11% on a vascular vs. non-vascular cause. Quality of documentation was fair. There was interobserver agreement on diagnosis of TIA in the majority of patients included in RS-TIA. Diagnostic accuracy may be further improved by more systematic documentation of symptoms and signs. © 2015 S. Karger AG, Basel.

Five-Year Mortality After Transient Ischemic Attack: Focus on Cardiometabolic Comorbidity and Hospital Readmission.

PubMed

Yousufuddin, Mohammed; Young, Nathan; Keenan, Lawrence; Olson, Tammy; Shultz, Jessica; Doyle, Taylor; Ahmmad, Eimad M; Arumaithurai, Kogulavadanan; Takahashi, Paul; Murad, Mohammad Hassan

2018-03-01

We aimed at providing estimates of mortality associated with cardiometabolic comorbidity and incident readmission from cardiometabolic as compared with noncardiometabolic conditions after a first transient ischemic attack. Between 2000 and 2015, patients hospitalized for a first transient ischemic attack were examined for cardiometabolic comorbidities (diabetes mellitus, coronary artery disease, heart failure, and atrial fibrillation), 5-year incident hospitalization, and time to death. Of 251 patients with transient ischemic attack, 134 (53%) had at least 1 and 55 (22%) had at least 2 cardiometabolic conditions. By 5 years, 491 readmissions (134 [27%] cardiometabolic and 357 [73%] noncardiometabolic) and 75 deaths (27 [36%] cardiometabolic and 47 [64%] noncardiometabolic) were observed. Mortality was increased with any concurrent cardiometabolic comorbidity (hazard ratio, 1.89; 95% confidence interval, 1.17-3.03; P =0.0089) with multiplicative mortality risk from a combination of coronary artery disease and heart failure. Each hospitalization was associated with a 1.5-fold risk of death (95% confidence interval, 1.37-1.64; P <0.0001). Risk of cardiometabolic and noncardiometabolic mortality was correlated with the corresponding category-specific readmission. Among patients hospitalized for first transient ischemic attack, 5-year mortality is associated with concurrent cardiometabolic comorbidity and rates of subsequent hospitalization. © 2018 American Heart Association, Inc.

Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients

PubMed Central

Yoo, Jung-Hwa; Yim, Sung-Vin

2018-01-01

Background Bojungikki-tang (BJIKT) is a widely used traditional herbal formula in China, Japan, and Korea. There have been reports that several herbs among BJIKT have interactions with antiplatelet drugs, such as aspirin. This study aimed to assess whether BJIKT interacts with aspirin in terms of pharmacokinetics (PK) and pharmacodynamics (PD) in healthy subjects and ischemic stroke patients. Methods The phase I interaction trial was a randomized, open-label, crossover study of 10 healthy male subjects, and the phase III interaction trial was a randomized, placebo-controlled, parallel study of 43 ischemic stroke patients. Each participant randomly received aspirin + BJIKT or aspirin + placebo. For PK analysis, plasma acetyl salicylic acid (ASA) and salicylic acid (SA) were evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2 (TxB2) were measured. Results In the PK parameters, mean area under curve, maximum concertation, and peak concentration time of ASA and SA were not different between two groups in healthy subjects and ischemic stroke patients. In the PD profiles, TxB2 concentrations and platelet aggregation were not affected by coadministration of BJIKT in healthy subjects and ischemic stroke patients. Conclusions These results suggest that coadministration of BJIKT with aspirin may not result in herb-drug interaction. PMID:29599812

Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke.

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Schmidt, Morten; Dekkers, Olaf M; Christiansen, Christian F; Pedersen, Lars; Bøtker, Hans Erik; Sørensen, Henrik T

2016-03-01

The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. © 2016 American Heart Association, Inc.

Relationship between activated clotting time and ischemic or hemorrhagic complications: analysis of 4 recent randomized clinical trials of percutaneous coronary intervention.

PubMed

Brener, Sorin J; Moliterno, David J; Lincoff, A Michael; Steinhubl, Steven R; Wolski, Kathy E; Topol, Eric J

2004-08-24

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications. We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001). In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.

[Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

PubMed

Dai, L; Guo, X; Huang, H J; Liao, X M; Luo, X Q; Li, D; Zhou, H; Gao, X C; Tan, M Y

2018-04-20

Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =7.496, 4.437, 5.402, P <0.05 or P <0.01). At PSH 48 and 72, protein expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group ( t =10.257, 15.055, P <0.01). (2) At PSH 48 and 72, the number of microvessel in ischemic zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group ( t =3.536, 4.000, P <0.05). (3) At PSH 24, 48, and 72, mRNA expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =4.406, 3.821, 3.356, P <0.05). At PSH 24 and 48, mRNA expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =4.113, 3.466, P <0.05). At PSH 72, mRNA expressions of CD31 in ischemic zone of wound of rats in 2 groups were close ( t =0.010, P >0.05). Conclusions: Exogenous HMGB1 can promote angiogenesis in ischemic zone of early scald wounds of rats by increasing expressions of VEGF and CD31.

Triple therapy greatly increases myocardial salvage during ischemia/reperfusion in the in situ rat heart.

PubMed

Yang, Xi-Ming; Cui, Lin; Alhammouri, Ahmad; Downey, James M; Cohen, Michael V

2013-10-01

Cangrelor, a P2Y12 receptor blocker, administered just prior to reperfusion reduced but did not eliminate myocardial infarction in rabbits. Combining cangrelor with ischemic postconditioning offered no additional protection suggesting they protected by a similar mechanism. To determine if cangrelor's protection might be additive to other cardioprotective interventions we tested cangrelor in combination with ischemic preconditioning, cariporide, a sodium-hydrogen exchange blocker, and mild hypothermia. Open-chest rats underwent 30-min coronary occlusion/2-h reperfusion. Cangrelor, administered as a bolus (60 μg/kg) 10 min before reperfusion and continued as an infusion (6 μg/kg/min) for the duration of the experiment, decreased infarction from 45.3 % of risk zone in control hearts to 25.0 %. Combining cangrelor and ischemic preconditioning offered no additional protection. Mild hypothermia (32-33 °C) instituted by peritoneal lavage with cold saline just prior to coronary occlusion resulted in 25.2 % infarction, and combining cangrelor and hypothermia nearly halved infarction to 14.1 % of risk zone. Cariporide (0.5 mg/kg) just prior to occlusion resulted in 27.2 % infarction and 15.8 % when combined with cangrelor. Combining cangrelor, hypothermia and cariporide further halved infarction to only 6.3 %. We also tested another P2Y12 inhibitor ticagrelor which is chemically similar to cangrelor. Ticagrelor (20 mg/kg) fed 1 h prior to surgery reduced infarct size by an amount similar to that obtained with cangrelor (25.6 % infarction), and this protective effect was abolished by chelerythrine and wortmannin, thus implicating participation of PKC and PI3-kinase, resp., in signaling. Cardioprotection from a P2Y12 receptor antagonist can be combined with at least 2 other strategies to magnify the protection. Combining multiple interventions that use different cardioprotective mechanisms could provide powerful protection against infarction in patients with acute coronary thrombosis.

Influence of statin therapy at time of stroke onset on functional outcome among patients with atrial fibrillation.

PubMed

Ko, Darae; Thigpen, Jonathan L; Otis, James A; Forster, Kristen; Henault, Lori; Quinn, Emily; Tripodis, Yorghos; Berger, Peter B; Limdi, Nita; Hylek, Elaine M

2017-01-15

Statin pretreatment has been associated with reduced infarct volume in nonlacunar strokes. The effect of statins on functional outcomes of strokes related to atrial fibrillation (AF) is unknown. We aimed to define the influence of prestroke statin use on functional outcome in AF. We assembled a cohort of consecutive ischemic stroke patients from 2006 to 2010. All patients underwent CT or MRI and were adjudicated by site investigators. AF was confirmed by electrocardiogram in 100% of patients. Site neurologists blinded to the study hypothesis affirmed the type of stroke and assessed the severity of disability at the time of hospital discharge. The frequency of death at 30-days was calculated. Ischemic stroke (n=1030) resulted in a severe neurological deficit or death (modified Rankin scale ≥4) at 30days in 711 patients (69%). Using multivariable logistic regression models adjusting for factors associated with statin treatment and factors associated with functional outcome, prestroke statin use was associated with a 32% reduction in frequency of severe stroke (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50-0.92; P=0.011). Other independent factors associated with severe stroke included older age, female sex, non-White race, diabetes mellitus, prior ischemic stroke, prior venous thromboembolism, and dementia. Ischemic strokes in AF are associated with high mortality and morbidity. Statin use at time of stroke onset among patients with AF was associated in this study with less severe stroke and warrant validation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ischemic time impacts biological integrity of phospho-proteins in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks.

PubMed

Holzer, Timothy R; Fulford, Angie D; Arkins, Austin M; Grondin, Janet M; Mundy, Christopher W; Nasir, Aejaz; Schade, Andrew E

2011-06-01

Post-translational modifications of proteins, such as phosphorylation, are labile events dynamically regulated by opposing kinase and phosphatase activities. Preanalytical factors, such as ischemic time before fixation, affect these activities and can have a significant impact on the ability to elucidate signaling pathways in tissue. Immunohistochemical analysis of phosphorylated proteins involved in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks was performed in human cell line xenografts from lung, brain, ovary, and prostate tumors. In order to replicate real-world practices, the tissues were subjected to ischemic times of 0 (baseline), 1, 4, and 24 hours before fixation in formalin. Two key concepts emerge from this analysis: (1) the stability of different phospho-epitopes within a given tumor type is variable (e.g. phospho-PRAS40 is more labile than phospho-S6 ribosomal protein) and (2) the stability of a given phospho-epitope (e.g. phospho-MAPKAPK2) varies significantly across different tumor types. These results highlight the importance of proper tissue acquisition and rapid fixation to preserve the biological integrity of signal transduction pathways that may guide therapeutic decision making.

Effect of Temperature on Heart Rate Variability in Neonatal ICU Patients With Hypoxic-Ischemic Encephalopathy.

PubMed

Massaro, An N; Campbell, Heather E; Metzler, Marina; Al-Shargabi, Tareq; Wang, Yunfei; du Plessis, Adre; Govindan, Rathinaswamy B

2017-04-01

To determine whether measures of heart rate variability are related to changes in temperature during rewarming after therapeutic hypothermia for hypoxic-ischemic encephalopathy. Prospective observational study. Level 4 neonatal ICU in a free-standing academic children's hospital. Forty-four infants with moderate to severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. Continuous electrocardiogram data from 2 hours prior to rewarming through 2 hours after completion of rewarming (up to 10 hr) were analyzed. Median beat-to-beat interval and measures of heart rate variability were quantified including beat-to-beat interval SD, low and high frequency relative spectral power, detrended fluctuation analysis short and long α exponents (αS and αL), and root mean square short and long time scales. The relationships between heart rate variability measures and esophageal/axillary temperatures were evaluated. Heart rate variability measures low frequency, αS, and root mean square short and long time scales were negatively associated, whereas αL was positively associated, with temperature (p < 0.01). These findings signify an overall decrease in heart rate variability as temperature increased toward normothermia. Measures of heart rate variability are temperature dependent in the range of therapeutic hypothermia to normothermia. Core body temperature needs to be considered when evaluating heart rate variability metrics as potential physiologic biomarkers of illness severity in hypoxic-ischemic encephalopathy infants undergoing therapeutic hypothermia.

Change of short-term memory effect in acute ischemic ventricular myocardium: a computational study.

PubMed

Mei, Xi; Wang, Jing; Zhang, Hong; Liu, Zhi-cheng; Zhang, Zhen-xi

2014-02-01

The ionic mechanism of change in short-term memory (STM) during acute myocardial ischemia has not been well understood. In this paper, an advanced guinea pig ventricular model developed by Luo and Rudy was used to investigate STM property of ischemic ventricular myocardium. STM response was calculated by testing the time to reach steady-state action potential duration (APD) after an abrupt shortening of basic cycling length (BCL) in the pacing protocol. Electrical restitution curves (RCs), which can simultaneously visualize multiple aspects of APD restitution and STM, were obtained from dynamic and local S1S2 restitution portrait (RP), which consist of a longer interval stimulus (S1) and a shorter interval stimulus (S2). The angle between dynamic RC and local S1S2 RC reflects the amount of STM. Our results indicated that compared with control (normal) condition, time constant of STM response in the ischemic condition decreased significantly. Meanwhile the angle which reflects STM amount is less in ischemic model than that in control model. By tracking the effect of ischemia on intracellular ion concentration and membrane currents, we declared that changes in membrane currents caused by ischemia exert subtle influences on STM; it is only the decline of intracellular calcium concentration that give rise to the most decrement of STM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Utilization of intravenous tissue plasminogen activator for ischemic stroke: are there sex differences?

PubMed

Allen, Norrina B; Myers, Daniela; Watanabe, Emi; Dostal, Jackie; Sama, Danny; Goldstein, Larry B; Lichtman, Judith H

2009-01-01

We evaluated whether there were sex-related differences in the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke admitted to US academic medical centers. Medical records were abstracted for consecutive ischemic stroke patients admitted to 32 academic medical centers from January through June, 2004, as part of the University HealthSystem Consortium Ischemic Stroke Benchmarking Project. Multivariate logistic models were used to test for sex-related differences in the receipt of IV-tPA with adjustment for demographic and clinical factors. The study included 1,234 patients (49% women; mean age 66.6 years; 56% white). IV-tPA was given to 7% (6.5% of women versus 7.5% of men, p = 0.49). Women and men were equally likely to receive IV-tPA in risk-adjusted analyses (OR 1.02, 95% CI 0.64-1.64). Approximately 77% of women and men who did not receive IV-tPA did not meet the 3-hour treatment window or their time of onset was unknown. Women admitted to academic hospitals receive IV-tPA as often as men; however, a substantial percentage of both women and men are not arriving within the 3-hour time window required for diagnostic assessment and administration of intravenous thrombolytic therapy. Additional efforts are needed to improve the rapid identification, evaluation and treatment of stroke patients.

Cell free DNA: A Novel Predictor of Neurological Outcome after Intravenous Thrombolysis and/or Mechanical Thrombectomy in Acute Ischemic Stroke Patients

PubMed Central

Wijatmiko, Teddy; Vajpeyee, Manisha; Taywade, Onjal

2018-01-01

Purpose Several blood markers have been evaluated in stroke patients, but their role remains limited in clinical practice. This study was designed to evaluate the utility of cell free DNA (cf DNA) in stroke patients undergoing therapeutic intervention in the form of mechanical thrombectomy in acute ischemic stroke patients. Materials and Methods Twenty-six patients with ischemic stroke who were managed with interventions like intravenous thrombolysis (IVT) and mechanical thrombectomy were recruited consecutively in this study. The cf DNA was extracted by using circulating nucleic acid kit and measured by real-time quantitative PCR assay for β-globin gene. The neurological outcome was measured by modified Rankin scale (mRS) score at three months after the onset of symptoms. Results Cf DNA levels correlated with severity of stroke at the time of admission (r=0.421, P=0.032) and poor outcome at three months (r=0.606, P=0.001). Therapeutic intervention in the form of mechanical thrombectomy or IVT was associated with improved outcome in patients with cf DNA <10,000 kilogenome-equivalents/L (P=<0.05). Conclusion Cf DNA level correlated well with the 3 month outcome in acute ischemic stroke patients. It can be a potential supplementary marker to predict neurological outcome after therapeutic intervention. PMID:29535894

Streamlining Workflow for Endovascular Mechanical Thrombectomy: Lessons Learned from a Comprehensive Stroke Center.

PubMed

Wang, Hongjin; Thevathasan, Arthur; Dowling, Richard; Bush, Steven; Mitchell, Peter; Yan, Bernard

2017-08-01

Recently, 5 randomized controlled trials confirmed the superiority of endovascular mechanical thrombectomy (EMT) to intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. The implication is that our health systems would witness an increasing number of patients treated with EMT. However, in-hospital delays, leading to increased time to reperfusion, are associated with poor clinical outcomes. This review outlines the in-hospital workflow of the treatment of acute ischemic stroke at a comprehensive stroke center and the lessons learned in reduction of in-hospital delays. The in-hospital workflow for acute ischemic stroke was described from prehospital notification to femoral arterial puncture in preparation for EMT. Systematic review of literature was also performed with PubMed. The implementation of workflow streamlining could result in reduction of in-hospital time delays for patients who were eligible for EMT. In particular, time-critical measures, including prehospital notification, the transfer of patients from door to computed tomography (CT) room, initiation of intravenous thrombolysis in the CT room, and the mobilization of neurointervention team in parallel with thrombolysis, all contributed to reduction in time delays. We have identified issues resulting in in-hospital time delays and have reported possible solutions to improve workflow efficiencies. We believe that these measures may help stroke centers initiate an EMT service for eligible patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Significance of coupling device for vessel anastomosis in esophageal reconstruction.

PubMed

Watanabe, Y; Horiuchi, A; Yamamoto, Y; Kikkawa, H; Kusunose, H; Sugishita, H; Sato, K; Yoshida, M; Yukumi, S; Kawachi, K

2005-01-01

To prevent an anastomotic failure due to impaired blood supply, several trials have been performed such as preoperative ischemic conditioning by transarterial embolization of the left gastric, right gastric and splenic arteries or microvascular anastomosis. We assess the significance of an automatic anastomotic coupling device for vessel anastomosis, which we have continuously utilized, to simplify the task and shorten the anastomotic time since March 1999. 8 patients who underwent venous anastomosis by an automatic anastomotic coupling device were evaluated for the time of anastomosis, total ischemic time and outcomes. Venous anastomosis was completed within 5 minutes on average. Microscopic arterial anastomosis by hand took 35 minutes on average. For gastric tube reconstruction, venous anastomosis by an automatic coupling device took only 5 minutes. The top of the gastric tube showed congestion before venous anastomosis, but rapidly recovered from it after anastomosis. Postoperative endoscopic observation of the mucosal color of the replaced intestine or gastric tube was started 3 days after surgery and revealed no ischemia or congestion. The postoperative course was uneventful except one case suffering from pneumonia but leakage was not observed in any case. An automatic anastomotic coupling device can perform an easy and reliable vascular anastomosis for patients who undergo esophageal reconstruction. The device may shorten the operating time and consequently the ischemic time of the gastric tube or jejunal or colonic graft, which in turn may lead to a decrease of complications.

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke

PubMed Central

Delgado-Mederos, Raquel; Gregori-Pla, Clara; Zirak, Peyman; Blanco, Igor; Dinia, Lavinia; Marín, Rebeca; Durduran, Turgut; Martí-Fàbregas, Joan

2018-01-01

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time. PMID:29541519

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke.

PubMed

Delgado-Mederos, Raquel; Gregori-Pla, Clara; Zirak, Peyman; Blanco, Igor; Dinia, Lavinia; Marín, Rebeca; Durduran, Turgut; Martí-Fàbregas, Joan

2018-03-01

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time.

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

PubMed

Li, Yongnan; Zeng, Qingdong; Liu, Gang; Du, Junzhe; Gao, Bingren; Wang, Wei; Zheng, Zhe; Hu, Shengshou; Ji, Bingyang

2017-11-01

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Cold acclimation and cognitive performance: A review.

PubMed

Jones, Douglas M; Bailey, Stephen P; Roelands, Bart; Buono, Michael J; Meeusen, Romain

2017-12-01

Athletes, occupational workers, and military personnel experience cold temperatures through cold air exposure or cold water immersion, both of which impair cognitive performance. Prior work has shown that neurophysiological pathways may be sensitive to the effects of temperature acclimation and, therefore, cold acclimation may be a potential strategy to attenuate cold-induced cognitive impairments for populations that are frequently exposed to cold environments. This review provides an overview of studies that examine repeated cold stress, cold acclimation, and measurements of cognitive performance to determine whether or not cold acclimation provides beneficial protection against cold-induced cognitive performance decrements. Studies included in this review assessed cognitive measures of reaction time, attention, logical reasoning, information processing, and memory. Repeated cold stress, with or without evidence of cold acclimation, appears to offer no added benefit of improving cognitive performance. However, research in this area is greatly lacking and, therefore, it is difficult to draw any definitive conclusions regarding the use of cold acclimation to improve cognitive performance during subsequent cold exposures. Given the current state of minimal knowledge on this topic, athletes, occupational workers, and military commands looking to specifically enhance cognitive performance in cold environments would likely not be advised to spend the time and effort required to become acclimated to cold. However, as more knowledge becomes available in this area, recommendations may change. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term efficacy of single procedure remote magnetic catheter navigation for ablation of ischemic ventricular tachycardia: a retrospective study.

PubMed

Dinov, Borislav; Schönbauer, Robert; Wojdyla-Hordynska, Agnieska; Braunschweig, Frieder; Richter, Sergio; Altmann, David; Sommer, Philipp; Gaspar, Thomas; Bollmann, Andreas; Wetzel, Ulrike; Rolf, Sascha; Piorkowski, Christopher; Hindricks, Gerhard; Arya, Arash

2012-05-01

Remote magnetic navigation (RMN) aims to reduce some inherent limitations of manual radiofrequency (RF) ablation. However, data comparing the effectiveness of both methods are scarce. This study evaluated the acute and long-term success of RMN guided versus manual RF ablation in patients with ischemic sustained ventricular tachycardia (sVT). One hundred two consecutive patients (age 68 ± 10 years, LVEF 32 ± 12%, 88 men) with ischemic sVT were ablated with RMN (Stereotaxis; 49%) or manually (51%) using substrate and/or activation mapping (Carto) and open-irrigated-tip catheters. All received implantable defibrillators or loop recorders. Acute success was defined as noninducibility of any sVT at the end of the ablation procedure and long-term success as freedom from VT upon follow-up. There was no difference in the baseline characteristics between the groups. Three patients died in hospital. Acute success rate was similar for RMN and manual ablation (82% vs 71%, P = 0.246). RMN was associated with significantly shorter fluoroscopy time (13 ± 12 minutes vs 32 ± 17 minutes, P = 0.0001) and RF time (2337.59 ± 1248.22 seconds vs 1589.95 ± 1047.42 seconds, P = 0.049), although total procedure time was similar (157 ± 40 minutes vs 148 ± 50 minutes, P = 0.42). There was a nonsignificant trend toward better long-term success in RMN group: after a median of 13 (range 1-34) months, 63% in the RMN and 53% in the manual ablation group were free from VT recurrence (P = 0.206). RMN guided RF ablation of ischemic sustained VT is equally efficient compared with manual ablation in terms of acute and long-term success rate. These results are achieved with a significantly reduced fluoroscopy time and shorter RF time. © 2012 Wiley Periodicals, Inc.

Risk factors for ischemic stroke and its subtypes in Chinese vs. Caucasians: Systematic review and meta-analysis.

PubMed

Tsai, Chung-Fen; Anderson, Niall; Thomas, Brenda; Sudlow, Cathie L M

2015-06-01

Chinese populations are reported to have a different distribution of ischemic stroke subtypes compared with Caucasians. To understand this better, we aimed to evaluate the differences in prevalence of risk factors in ischemic stroke and their distributions among ischemic stroke subtypes in Chinese vs. Caucasians. We systematically sought studies conducted since 1990 with data on frequency of risk factors among ischemic stroke subtypes in Chinese or Caucasians. For each risk factor, we calculated study-specific and random effects pooled estimates in Chinese and Caucasians separately for: prevalence among ischemic stroke; odds ratios, comparing prevalence for each ischemic stroke subtype vs. all others. We included seven studies among 16,199 Chinese, and eleven among 16,189 Caucasian ischemic stroke patients. Risk factors studied were hypertension, diabetes, atrial fibrillation, ischemic heart disease, hypercholesterolemia, smoking and alcohol. Chinese ischemic stroke patients had younger onset of stroke than Caucasians, similar prevalence of hypertension, diabetes, smoking and alcohol, and significantly lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia. Risk factor associations with ischemic stroke subtypes were mostly similar among Chinese and Caucasian ischemic stroke patients. Compared with all other ischemic subtypes, diabetes was more common in large artery stroke, atrial fibrillation and ischemic heart disease in cardioembolic stroke, and hypertension and diabetes in lacunar stroke. Our study showed a lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia in Chinese, and mostly similar risk factor associations in Chinese and Caucasian ischemic stroke patients. Further analyses of individual patient data to allow adjustment for confounders are needed to confirm and extend these findings. © 2015 World Stroke Organization.

Upregulation of Fibronectin and the α5β1 and αvβ3 Integrins on Blood Vessels within the Cerebral Ischemic Penumbra

PubMed Central

Li, Longxuan; Liu, Fudong; Welser-Alves, Jennifer V.; McCullough, Louise D.; Milner, Richard

2012-01-01

Following focal cerebral ischemia, blood vessels in the ischemic border, or penumbra, launch an angiogenic response. In light of the critical role for fibronectin in angiogenesis, and the observation that fibronectin and its integrin receptors are strongly upregulated on angiogenic vessels in the hypoxic CNS, the aim of this study was to establish whether angiogenic vessels in the ischemic CNS also show this response. Focal cerebral ischemia was established in C57/Bl6 mice by middle cerebral artery occlusion (MCA:O), and brain tissue analyzed seven days following re-perfusion, a time at which angiogenesis is ongoing. Within the ischemic core, immunofluorescent (IF) studies demonstrated vascular expression of MECA-32, a marker of leaky cerebral vessels, and vascular breakdown, defined by loss of staining for the endothelial marker, CD31, and the vascular adhesion molecules, laminin, dystroglycan and α6 integrin. Within the ischemic penumbra, dual-IF with CD31 and Ki67 revealed the presence of proliferating endothelial cells, indicating ongoing angiogenesis. Significantly, vessels in the ischemic penumbra showed strong upregulation of fibronectin and the fibronectin receptors, α5β1 and αvβ3 integrins. Taken together with our recent finding that the α5β1 integrin plays an important role in promoting cerebral angiogenesis in response to hypoxia, these results suggest that stimulation of the fibronectin-α5β1 integrin signalling pathway may provide a novel approach to amplifying the intrinsic angiogenic response to cerebral ischemia. PMID:22056225

Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ching-Chih; Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan; Tumor Center, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival ratemore » between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.« less

Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke

PubMed Central

Bentley, Paul; Hamady, Mohammad; Marley, Stephen; Davis, John; Shlebak, Abdul; Nicholls, Joanna; Williamson, Deborah A.; Jensen, Steen L.; Gordon, Myrtle; Habib, Nagy; Chataway, Jeremy

2014-01-01

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age >80 years (n = 19); medical instability (n = 17), and significant carotid stenosis (n = 13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials. PMID:25107583

External detection of regional myocardial metabolism with radioiodinated hexadecenoic acid in the dog heart.

PubMed

van der Wall, E E; Westera, G; den Hollander, W; Visser, F C

1981-04-01

In a previous study we have demonstrated that terminally iodinated hexadecenoic acid (131I-HA) and Thallium-201 (201T1) are comparable in myocardial uptake and distribution in the ischemic dog heart (Westera et al. 1980). In the present study the potential value of 131I-HA was proved in determining regional myocardial metabolism in 19 dog experiments. In ten dogs, 131I-HA was administered 5 min after occlusion of a coronary artery (group II), in six dogs after a 90 min occlusion period (group III). Three dogs served as controls (group I). The turnover rates (t 1/2) of 131I-HA were calculated from mono-exponential time-activity curves, obtained by external detection over ischemic and normally perfused areas during a 30 min period after IV injection of 0.7-1.5 mCi 131I-HA. The t 1/2 values in ischemic regions were found to be significantly longer (group II, 25.1 +/- 2.6 min; group III, 22.6 +/- 1.8 min) than in non-ischemic areas (group II, 12.5 +/- 1.8 min; group III, 14.2 +/- 1.4 min). The t 1/2 values in the control dogs (group I, 13.4 +/- 1.4 min) were not significantly different from the turnover rates in the non-ischemic areas of the occluded hearts. We conclude that the study of turnover rates of radioiodinated free fatty acids allows the determination of regional myocardial metabolism and offers a means to distinguish normally perfused from ischemic myocardial tissue.

Comprehensive CT Evaluation in Acute Ischemic Stroke: Impact on Diagnosis and Treatment Decisions

PubMed Central

Löve, Askell; Siemund, Roger; Andsberg, Gunnar; Cronqvist, Mats; Holtås, Stig; Björkman-Burtscher, Isabella

2011-01-01

Background. With modern CT imaging a comprehensive overview of cerebral macro- and microcirculation can be obtained within minutes in acute ischemic stroke. This opens for patient stratification and individualized treatment. Methods. Four patients with acute ischemic stroke of different aetiologies and/or treatments were chosen for illustration of the comprehensive CT protocol and its value in subsequent treatment decisions. The patients were clinically evaluated according to the NIHSS-scale, examined with the comprehensive CT protocol including both CT angiography and CT perfusion, and followed up by MRI. Results. The comprehensive CT examination protocol increased the examination time but did not delay treatment initiation. In some cases CT angiography revealed the cause of stroke while CT perfusion located and graded the perfusion defect with reasonable accuracy, confirmed by follow-up MR-diffusion. In the presented cases findings of the comprehensive CT examination influenced the treatment strategy. Conclusions. The comprehensive CT examination is a fast and safe method allowing accurate diagnosis and making way for individualized treatment in acute ischemic stroke. PMID:21603175

Remote ischemic preconditioning with a specialized protocol activates the non-neuronal cardiac cholinergic system and increases ATP content in the heart.

PubMed

Oikawa, Shino; Mano, Asuka; Takahashi, Rina; Kakinuma, Yoshihiko

2015-11-01

Ischemic preconditioning (IPC) renders the targeted organ resistant to prolonged ischemic insults, leading to organoprotection. Among several means to achieve IPC, we reported that remote ischemic preconditioning (RIPC) activates the non-neuronal cardiac cholinergic system (NNCCS) to accelerate de novo ACh synthesis in cardiomyocytes. In the current study, we aimed to optimize a specific protocol to most efficiently activate NNCCS using RIPC. In this study, we elucidated that the protocol with 3 min of ischemia repeated three times increased cardiac ChAT expression (139.2 ± 0.4%; P < 0.05) as well as ACh (14.2 ± 2.0× 10(-8) M; P< 0.05) and ATP content (2.13 ± 0.19 μmol/g tissue; P < 0.05) in the heart. Moreover, in the specific protocol, several characteristic responses against energy starvation and for obtaining adequate energy were observed; therefore, it is suggested that RIPC evokes a robust response by the heart to activate NNCCS through the modification of energy metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

Stroke onset time estimation from multispectral quantitative magnetic resonance imaging in a rat model of focal permanent cerebral ischemia.

PubMed

McGarry, Bryony L; Rogers, Harriet J; Knight, Michael J; Jokivarsi, Kimmo T; Sierra, Alejandra; Gröhn, Olli Hj; Kauppinen, Risto A

2016-08-01

Quantitative T2 relaxation magnetic resonance imaging allows estimation of stroke onset time. We aimed to examine the accuracy of quantitative T1 and quantitative T2 relaxation times alone and in combination to provide estimates of stroke onset time in a rat model of permanent focal cerebral ischemia and map the spatial distribution of elevated quantitative T1 and quantitative T2 to assess tissue status. Permanent middle cerebral artery occlusion was induced in Wistar rats. Animals were scanned at 9.4T for quantitative T1, quantitative T2, and Trace of Diffusion Tensor (Dav) up to 4 h post-middle cerebral artery occlusion. Time courses of differentials of quantitative T1 and quantitative T2 in ischemic and non-ischemic contralateral brain tissue (ΔT1, ΔT2) and volumes of tissue with elevated T1 and T2 relaxation times (f1, f2) were determined. TTC staining was used to highlight permanent ischemic damage. ΔT1, ΔT2, f1, f2, and the volume of tissue with both elevated quantitative T1 and quantitative T2 (V(Overlap)) increased with time post-middle cerebral artery occlusion allowing stroke onset time to be estimated. V(Overlap) provided the most accurate estimate with an uncertainty of ±25 min. At all times-points regions with elevated relaxation times were smaller than areas with Dav defined ischemia. Stroke onset time can be determined by quantitative T1 and quantitative T2 relaxation times and tissue volumes. Combining quantitative T1 and quantitative T2 provides the most accurate estimate and potentially identifies irreversibly damaged brain tissue. © 2016 World Stroke Organization.

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging.

PubMed

Guang, Huizhi; Cai, Chuangjian; Zuo, Simin; Cai, Wenjuan; Zhang, Jiulou; Luo, Jianwen

2017-03-01

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Development of wireless monitoring system based on Zigbee technology in blood and bacterin cold chain].

PubMed

Zhao, Peng; Sun, Jian-Jun; Wu, Tai-Hu

2008-11-01

Real-time monitoring for temperature is required in cold chain for the medical products that are sensible with temperature, such as blood and bacterin, to guarantee the quality and reduce their wastage. This wireless monitoring system in cold chain is developed with Zigbee technology. Functions such as real-time monitoring, analyzing, alarming are realized. The system boasts such characteristics as low power consumption, low cost, big capacity and high reliability, and could improve the capability of real-time monitoring and management in cold chain effectively.

Smoking, leisure-time exercise and frequency of self-reported common cold among the general population in northeastern China: a cross-sectional study.

PubMed

Zhou, Ge; Liu, Hongjian; He, Minfu; Yue, Mengjia; Gong, Ping; Wu, Fangyuan; Li, Xuanxuan; Pang, Yingxin; Yang, Xiaodi; Ma, Juan; Liu, Meitian; Li, Jinghua; Zhang, Xiumin

2018-02-27

Physical activity (PA) and smoking have been reported to be associated with the duration and severity of common cold symptoms. However, few studies have addressed the associations between the frequency of leisure-time exercise, cigarette smoking status and the frequency of the common cold in a cold area. This study was designed to investigate these issues in northeastern China. This cross-sectional study included individuals who participated in a regular health examination conducted in Jilin Province, China. Information on episodes of the common cold, the frequency of leisure-time exercise and cigarette smoking status in the past year were collected by self-administered health questionnaires. Ordinal logistic regression models were used to analyse the associations between the frequency of leisure-time exercise, cigarette smoking status and the retrospective frequency of common cold. A total of 1413 employees participated in the study, with an average age of 38.92 ± 9.04 years and 44.4% of them were male. Of all participants, 80.8% reported having experienced the common cold in the past year. After adjustment, the risk of suffering from the common cold more than once (odds ratios (ORs), 1.59; 95% confidence interval (CI), 1.27-1.99) in passive smokers was 1.59 times as high as that in non-smokers. Nevertheless, the results of the adjusted analysis showed no statistically significant relation between current smoking and the frequency of the common cold. A high frequency of leisure-time exercise (≥3 days/week) was associated with a 26% reduced risk of having at least one episode of the common cold (OR, 0.74; 95% CI, 0.55-0.98) compared with a low frequency group (< 4 days/month). For current and passive smokers, the protective effect of a high frequency of leisure-time exercise appears not to be obvious (current smokers: OR, 0.68; 95% CI, 0.33-1.43; passive smokers: OR, 1.15; 95% CI, 0.69-1.93). Passive smoking was associated with a higher risk of having self-reported common cold at least once, while a high frequency of leisure-time exercise was related to a lower risk of reporting more than one episode of the disease in Chinese.

Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial.

PubMed

Sales, Arthur H A; Barz, Melanie; Bette, Stefanie; Wiestler, Benedikt; Ryang, Yu-Mi; Meyer, Bernhard; Bretschneider, Martin; Ringel, Florian; Gempt, Jens

2017-07-25

Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume. Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm 3 (interquartile range (IR): 0.0-2.35) in the rIPC group compared with 1.30 cm 3 (IR: 0.29-3.66) in the control group (p = 0.09). Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery. German Clinical Trials Register, DRKS00010409 . Retrospectively registered on 13 October 2016.

The APOE E4 Allele Confers Increased Risk of Ischemic Stroke Among Greek Carriers.

PubMed

Konialis, Christopher; Spengos, Konstantinos; Iliopoulos, Panagiotis; Karapanou, Sophia; Gialafos, Elias; Hagnefelt, Birgitta; Vemmos, Konstantinos; Zakopoulos, Nikolaos; Pangalos, Constantinos

2016-01-01

Although several studies in various countries have indicated that the presence of the E4 allele of the apolipoprotein-E (APOE) gene is a risk factor for ischemic cerebrovascular disease, the strength of this association still remains a matter of debate. The aim of the study was to determine the frequency of the APOE E4 allele and various other gene polymorphisms in in a well-characterized sample of Greek patients and to evaluate the potential associations with the risk of ischemic stroke (IS) and coronary heart disease (CHD). A total of nine gene variants/polymorphisms - F5 (Leiden - R5 06Q, rs6025), F2 (20210G > A, rs1799963), F13A1 (V34L, rs5985), MTHFR (677C > T - A222V, rs1801133), MTHFR (1298A > C - E429A, rs1801131), FGB (-455G > A -c.-463G > A; rs1800790), SERPINE1 (PAI14G/5G - rs1799889), ACE (ACE I/D, rs1799752), ITGB3 (GPIIIa L33P, rs5918) and the APOE E2/E3/E4 alleles (rs7412, rs429358) - were genotyped in 200 newly diagnosed ischemic stroke (IS) patients, 165 patients with ischemic coronary heart disease (CHD) and 159 controls with no cerebroor cardiovascular disease (non-CVD). A statistical analysis was performed using univariate and multivariate logistic regression models. No significant association was found regarding most gene polymorphisms and the presence of IS or CHD in the patient cohort. However, the APOE E4 allele frequency was significantly higher (p = 0.02) among patients with ischemic stroke (IS) or IS + CHD (12.7%) when compared to the controls (5.1%). More accurately, E4 carriers had 2.66 and 2.71 times greater likelihood of IS or IS + CHD than non-carriers, respectively (OR = 2.66, 95% CI 1.39-5.07, OR = 2.71, 95% CI 0.98-7.48). In contrast to some previous studies, these results support the role of the APOE E4 allele as an independent risk factor for ischemic stroke and ischemic coronary heart disease among Greek patients.

The mechanism of protection from 5 (N-ethyl-N-isopropyl)amiloride differs from that of ischemic preconditioning in rabbit heart.

PubMed

Sato, H; Miki, T; Vallabhapurapu, R P; Wang, P; Liu, G S; Cohen, M V; Downey, J M

1997-10-01

We investigated the effects of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on infarction in isolated rabbit hearts and cardiomyocytes. Thirty min of regional ischemia caused 29.6 +/- 2.8% of the risk zone to infarct in untreated Krebs buffer-perfused hearts. Treatment with EIPA (1 microM) for 20 min starting either 15 min before ischemia or 15 min after the onset of ischemia significantly reduced infarction to 5.4 +/- 2.0% and 7.0 +/- 1.0%, respectively (p < 0.01 versus untreated hearts). In both cases salvage was very similar to that seen with ischemic preconditioning (PC) (7.1 +/- 1.5% infarction). Unlike the case with ischemic preconditioning, however, protection from EIPA was not blocked by 50 microM polymyxin B, a PKC inhibitor, or 1 microM glibenclamide, a KATP channel blocker. Forty-five min of regional ischemia caused 51.0 +/- 2.9% infarction in untreated hearts. Ischemic preconditioning reduced infarction to 23.4 +/- 3.1% (p < 0.001 versus untreated hearts). In these hearts with longer periods of ischemia pretreatment with EIPA reduced infarction similarly to 28.8 +/- 2.1% (p < 0.01 versus untreated hearts). However, when EIPA was combined with ischemic PC, no further reduction in infarction was seen (23.8 +/- 3.5% infarction). To further elucidate the mechanism of EIPA's cardioprotective effect, this agent was also examined in isolated rabbit cardiomyocytes. Preconditioning caused a delay of about 30 min in the progressive increase in osmotic fragility that occurs during simulated ischemia. In contrast, EIPA had no effect on the time course of ischemia-induced osmotic fragility. Furthermore, EIPA treatment did not alter the salutary effect of ischemic preconditioning when the two were combined in this model. We conclude that Na+/H+ exchange inhibition limits myocardial infarction in the isolated rabbit heart by a mechanism which is quite different from that of ischemic preconditioning. Despite the apparently divergent mechanisms, EIPA's cardioprotective effect could not be added to that of ischemic or metabolic preconditioning in these models.

Ischemic Strokes (Clots)

MedlinePlus

... Month Infographic Stroke Hero F.A.S.T. Quiz Ischemic Strokes (Clots) Updated:May 21,2018 Ischemic stroke accounts for about 87 percent of all cases. View a detailed animation of ischemic stroke . Ischemic strokes occur as a result of an ...

Viscosity of dysphagia-oriented cold-thickened beverages: effect of setting time at refrigeration temperature.

PubMed

Kim, Sung-Gun; Yoo, Byoungseung

2015-01-01

Although extensive literature is available on the viscosity of thickened beverages with food thickeners, no attempt has been made to study the effect of setting time on the viscosity of pudding-like cold-thickened beverages with xanthan gum (XG)-based thickeners by using a rheometer. In particular, it is of considerable practical importance to investigate the effect of setting time on their viscosity at 5°C because some cold-thickened beverages will be prepared in the kitchen in bulk and stored at 5°C before serving or consuming rather than serving immediately upon mixing with thickeners. To examine the effect of different setting times (15-120 min) on the viscosity of cold-thickened beverages prepared with various XG-based food thickeners, and also to compare the viscosity differences among the various cold beverages and XG-based food thickeners in beverage-thickener mixture systems. Four commercially available XG-based food thickeners (A-D) and three cold beverages (water, orange juice and milk) were used for the preparation of cold-thickened beverages. The thickened sample was portioned into six samples for the designated setting times and then stored at 5°C over setting time. Their apparent viscosity (η(a,50)) at 50 s(-1) was measured using a rheometer. The largest increases in η(a,50) values for thickened beverages, except for water, were observed at 15 min (p < 0.05), showing a pudding-like fluid, and at longer time periods their η(a,50) values gradually increased or were constant with an increase in setting time. The percentage increase in viscosity values at different setting times (15-120 min) as compared with the control (0 min) was less pronounced in the thickened orange juice and milk samples with thickener A over setting time, indicating that the thickened beverages with thickener A had more stable structure compared with those with other thickeners (B-D) over time. Statistical analysis showed that changes in the viscosity of cold-thickened beverages over setting time are greatly influenced by the type of beverages and thickeners. Cold-thickened beverages should be carefully prepared with instant commercial XG-based food thickeners because they produced different thickening patterns over setting time which clinicians must consider for a safe and easy swallowing. The information presented in this study will provide both clinicians and patients with additional knowledge to prepare cold-thickened beverages with the corrected viscosity for safe swallowing. © 2014 Royal College of Speech and Language Therapists.

Efficacy of cold light bleaching using different bleaching times and their effects on human enamel.

PubMed

Wang, Wei; Zhu, Yuhe; Li, Jiajia; Liao, Susan; Ai, Hongjun

2013-01-01

This study investigated the efficacy of cold light bleaching using different bleaching times and the effects thereof on tooth enamel. Before and after bleaching, stained tooth specimens were subjected to visual and instrumental colorimetric assessments using Vita Shade Guide and spectrophotometric shade matching. Enamel surface alterations were examined using scanning electron microscopy (SEM) to analyze surface morphology, surface microhardness (SMH) measurement to determine changes in mechanical properties, and X-ray diffraction (XRD) to characterize post-bleaching enamel composition. Cold light bleaching successfully improved tooth color, with optimal efficacy when bleaching time was beyond 10 min. Significant differences in surface morphology were observed among the different bleaching times, but no significant differences were observed for enamel composition and surface microhardness among the different bleaching times. Results of this study revealed an association between the bleaching time of cold light bleaching and its whitening efficacy. Together with the results on enamel surface changes, this study provided positive evidence to support cold light bleaching as an in-office bleaching treatment.

Breath-hold times in air compared to breath-hold times during cold water immersions.

PubMed

Taber, Michael J; MacKinnon, Scott N; Power, Jonathan; Walker, Robert

2015-02-01

Given the effects of cold water immersion on breath-hold (BH) capabilities, a practical training exercise was developed for military/paramilitary personnel completing a helicopter underwater egress training (HUET) program. The exercise was designed to provide firsth and experience of the effects of cold water exposure on BH time. After completing the required HUET, 47 subjects completed two BH testing sessions as well as a short questionnaire. The first BH was completed while standing on the pool deck. The second BH was completed while fully immersed (face down) in 2-3°C water. There were 40 of the volunteers who also breathed from an emergency breathing system (EBS) while in the cold water. Results demonstrated that BH capabilities in cold water were significantly lower than those in ambient air. A significant correlation was also found between BH in air and the difference in cold water vs. air BH capabilities, which suggests that subjects who can hold their breath the longest in air experienced the greatest decrease in BH when immersed. Results indicate that 92% of the subjects reported that the practical cold water immersion exercise had a high value. Finally, 58% of those who used the EBS reported that it was harder to breathe in cold water than while in the training pool (approximately 22°C). The BH times for this group were similar to those reported in previous cold water immersion studies. Based on the questionnaire results, it is possible, when carefully applied, to include a practical cold water immersion exercise into existing HUET programs.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

NASA Astrophysics Data System (ADS)

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Changes in NAA and lactate following ischemic stroke: a serial MR spectroscopic imaging study.

PubMed

Muñoz Maniega, S; Cvoro, V; Chappell, F M; Armitage, P A; Marshall, I; Bastin, M E; Wardlaw, J M

2008-12-09

Although much tissue damage may occur within the first few hours of ischemic stroke, the duration of tissue injury is not well defined. We assessed the temporal pattern of neuronal loss and ischemia after ischemic stroke using magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). We measured N-acetylaspartate (NAA) and lactate in 51 patients with acute ischemic stroke at five time points, from admission to 3 months, in voxels classified as normal, possibly or definitely abnormal (ischemic) according to the appearance of the stroke lesion on the admission DWI. We compared changes in NAA and lactate in different voxel classes using linear mixed models. NAA was significantly reduced from admission in definitely and possibly abnormal (p < 0.01) compared to contralateral normal voxels, reaching a nadir by 2 weeks and remaining reduced at 3 months. Lactate was significantly increased in definitely and possibly abnormal voxels (p < 0.01) during the first 5 days, falling to normal at 2 weeks, rising again later in these voxels. The progressive fall in N-acetylaspartate suggests that some additional neuronal death may continue beyond the first few hours for up to 2 weeks or longer. The mechanism is unclear but, if correct, then it is possible that interventions to limit this ongoing subacute tissue damage might add to the benefit of hyperacute treatment, making further improvements in outcome possible.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex.

PubMed

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Gene Variant and Level of IL-1β in Ischemic Stroke Patients With and Without Type 2 Diabetes Mellitus.

PubMed

Chehaibi, Khouloud; Hrira, Mohamed Yahia; Trabelsi, Imen; Escolà-Gil, Juan Carlos; Slimane, Mohamed Naceur

2015-11-01

Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to explore, for the first time, the relationship between IL-1β -31 T/C polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). One hundred ninety-six patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. IL-1β genotyping was performed by PCR-RFLP technique. After adjusting for sex, age, smoking, obesity, dyslipidemia, and hypertension, there was no significant difference in the distribution of IL-1β -31 T/C genotypes and allele frequencies between IS patients with or without type 2 diabetes mellitus and control group (p > 0.05). Moreover, a significant positive correlation between serum IL-1β level and glucose (p1 = 0.044) was showed. In addition, serum levels of IL-1β were found to be higher among TT genotype carriers than TC and CC genotype carriers in ischemic stroke patients with or without T2DM but these differences were not significant. These results indicate that IL-1β gene polymorphism might not be a risk factor in the development of ischemic stroke in Tunisian population.

Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population.

PubMed

Kumar, A; Prasad, M; Kathuria, P

2014-10-01

Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case-control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case-control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12-3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.

Risk of ischemic stroke after an acute myocardial infarction in patients with diabetes mellitus.

PubMed

Jakobsson, Stina; Bergström, Lisa; Björklund, Fredrik; Jernberg, Tomas; Söderström, Lars; Mooe, Thomas

2014-01-01

Incidence, any trend over time, and predictors of ischemic stroke after an acute myocardial infarction (AMI) in diabetic patients are unknown. Data for 173,233 unselected patients with an AMI, including 33,503 patients with diabetes mellitus, were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) during 1998 to 2008. Ischemic stroke events were recorded during 1 year of follow-up. Patients with diabetes mellitus more often had a history of cardiovascular disease, received less reperfusion therapy, and were treated with acetylsalicylic acid, P2Y12 inhibitors, and statins to a lesser extent compared with patients without diabetes mellitus. However, the use of evidence-based therapies increased markedly in both groups during the study period. The incidence of ischemic stroke during the first year after AMI decreased from 7.1% to 4.7% in patients with diabetes mellitus and from 4.2% to 3.7% in patients without diabetes mellitus. Risk reduction was significantly larger in the diabetic subgroup. Reperfusion therapy, acetylsalicylic acid, P2Y12 inhibitors, and statins were independently associated with the reduced stroke risk. Ischemic stroke is a fairly common complication after an AMI in patients with diabetes mellitus, but the risk of stroke has decreased during recent years. The increased use of evidence-based therapies contributes importantly to this risk reduction, but there is still room for improvement.

[Pharmacological study of nicergoline. (II). Protective effect on ischemic brain damages in animals].

PubMed

Shintomi, K; Itakura, T; Yoshimoto, K; Ogawa, Y; Fukushima, T; Matsuoka, Y

1986-04-01

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.

Toward a new cold and warm nondepolarizing, normokalemic arrest paradigm for orthotopic heart transplantation.

PubMed

Rudd, Donna M; Dobson, Geoffrey P

2009-01-01

Currently, the safe human heart preservation time is limited to around 4 to 5 hours of cold ischemic storage. Longer arrest times can lead to donor heart damage, early graft dysfunction, and chronic rejection. The aim of this study was to examine a new nondepolarizing, normokalemic preservation solution with adenosine and lidocaine for as long as 6 hours of arrest at cold and warmer storage temperatures. Isolated perfused rat hearts (n = 87) were switched from working to Langendorff (nonworking) mode and arrested at 37 degrees C with 200-micromol/L adenosine and 500-micromol/L lidocaine in Krebs-Henseleit buffer (10-mmol/L glucose, pH 7.7, 37 degrees C) or with Celsior (Sangstat Medical Corp, Fremont, CA). Hearts were removed and placed in static storage at 4 degrees C for 2 and 6 hours or remained on the apparatus and were intermittently flushed at 37 degrees C every 20 minutes for 2 minutes at 68 mm Hg (average arrest temperature 28 degrees -30 degrees C) for 2 and 6 hours. We further investigated the effect of the warmer adenosine-lidocaine solution supplemented with 1- or 5-mmol/L pyruvate. Adenosine-lidocaine solution arrested hearts in 16 +/- 2 seconds (n = 32), whereas Celsior did so in 39 +/- 4 seconds (n = 23). After 2 hours of cold static storage, there were no functional differences between the adenosine-lidocaine and Celsior groups, with approximately 70% return of cardiac output. In contrast, after 6 hours of 4 degrees C storage, adenosine-lidocaine hearts had significantly higher functional recoveries (68% +/- 5% cardiac output) than Celsior hearts (47% +/- 14% cardiac output) during 60 minutes of reperfusion. In addition, Celsior hearts took 5 minutes longer to reanimate and showed early reperfusion arrhythmias. At warmer temperatures after 2 hours of arrest, adenosine-lidocaine and Celsior hearts were not significantly different, despite a 43% higher cardiac output in adenosine-lidocaine hearts (80% +/- 3% vs 56% +/- 12%). After 6 hours, adenosine-lidocaine hearts had recovered 55% +/- 3% of prearrest cardiac output, which increased significantly to 75% +/- 4% with addition of 1-mmol/L pyruvate. Adenosine-lidocaine with 1-mmol/L pyruvate hearts spontaneously recovered 106% heart rate, 93% to 105% developed pressures, 70% aortic flow, and 81% coronary flow. Coronary vascular resistance increased 1.7- to 1.9-fold during the 6-hour arrest. In contrast, Celsior hearts did not have return of aortic or coronary flow after 6 hours in these warmer conditions. A new nondepolarizing, normokalemic adenosine-lidocaine arrest solution in Krebs-Henseleit buffer with 10-mmol/L glucose was versatile at both 4 degrees C and 28 degrees C to 30 degrees C relative to Celsior, and the addition of 1-mmol/L pyruvate significantly improved cardiac output at warmer arrest temperatures. This new arrest paradigm may be useful in the harvest, storage, and implantation of donor hearts.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy.

PubMed

Carreras, Nuria; Alsina, Miguel; Alarcon, Ana; Arca-Díaz, Gemma; Agut, Thais; García-Alix, Alfredo

To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4±1.4°C and mean transfer time was 3.3±2.0h. Mean age at arrival was 5.6±2.5h. Temperature at arrival was between 33 and 35°C in 41 (61%) infants, between 35°C and 36.5°C in 15 (22%) and <33°C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature<33°C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p<0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

PubMed Central

2011-01-01

Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions. PMID:21266064

Burden of Intracranial Atherosclerosis Is Associated With Long-Term Vascular Outcome in Patients With Ischemic Stroke.

PubMed

Kim, Byung-Su; Chung, Pil-Wook; Park, Kwang-Yeol; Won, Hong-Hee; Bang, Oh Young; Chung, Chin-Sang; Lee, Kwang Ho; Kim, Gyeong-Moon

2017-10-01

Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome. This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients. ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01-1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05-1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88-2.74) and 1.72 (1.17-2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71-2.30) and 1.95 (1.27-2.99), respectively. ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome. © 2017 American Heart Association, Inc.

Differences in lipid profiles in two Hispanic ischemic stroke populations.

PubMed

Arauz, A; Romano, J G; Ruiz-Franco, A; Shang, T; Dong, C; Rundek, T; Koch, S; Hernández-Curiel, B; Pacheco, J; Rojas, P; Ruiz-Navarro, F; Katsnelson, M; Sacco, R L

2014-06-01

The study aims to compare lipid profiles among ischemic stroke patients in a predominantly Caribbean-Hispanic population in Miami and a Mestizo Hispanic population in Mexico City. We analyzed ischemic stroke Hispanic patients with complete baseline fasting lipid profile enrolled contemporaneously in the prospective registries of two tertiary care teaching hospitals in Mexico City and Miami. Demographic characteristics, risk factors, medications, ischemic stroke subtype, and first fasting lipid profile were compared. Vascular risk factor definitions were standardized. Multiple linear regression analysis was performed to compare lipid fractions. A total of 324 patients from Mexico and 236 from Miami were analyzed. Mexicans were significantly younger (58 · 1 vs. 67 · 4 years), had a lower frequency of hypertension (53 · 4% vs. 79 · 7%), and lower body mass index (27 vs. 28 · 5). There was a trend toward greater prevalence of diabetes in Mexicans (31 · 5 vs. 24 · 6%, P = 0 · 07). Statin use at the time of ischemic stroke was more common in Miami Hispanics (18 · 6 vs. 9 · 4%). Mexicans had lower total cholesterol levels (169 · 9 ± 46 · 1 vs. 179 · 9 ± 48 · 4 mg/dl), lower low-density lipoprotein (92 · 3 ± 37 · 1 vs. 108 · 2 ± 40 · 8 mg/dl), and higher triglyceride levels (166 · 9 ± 123 · 9 vs. 149 · 2 ± 115 · 2 mg/dl). These differences remained significant after adjusting for age, gender, hypertension, diabetes, body mass index, smoking, ischemic stroke subtype, and statin use. We found significant differences in lipid fractions in Hispanic ischemic stroke patients, with lower total cholesterol and low-density lipoprotein, and higher triglyceride levels in Mexicans. These findings highlight the heterogeneity of dyslipidemia among the Hispanic race-ethnic group and may lead to different secondary prevention strategies. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography

PubMed Central

Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

2007-01-01

Background Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. Case Presentation A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Conclusion Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three-dimensional interactions between the mitral valve apparatus and the left ventricle. This aids in timely surgical planning. PMID:17894872

Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

PubMed

Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

2007-09-25

Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three-dimensional interactions between the mitral valve apparatus and the left ventricle. This aids in timely surgical planning.

Predictors of lung transplant survival in eurotransplant.

PubMed

Smits, J M A; Mertens, B J A; Van Houwelingen, H C; Haverich, A; Persijn, G G; Laufer, G

2003-11-01

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy.

PubMed

Jiang, Beisi; Churilov, Leonid; Kanesan, Lasheta; Dowling, Richard; Mitchell, Peter; Dong, Qiang; Davis, Stephen; Yan, Bernard

2017-05-01

Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) ( p =0.001), by 73.9% in diastolic BP (DBP) ( p <0.001) and by 68.5% in mean BP (MBP) ( p <0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP ( p =0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship ( p >0.05). In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.

Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE.

PubMed

Pan, Yuesong; Jing, Jing; Chen, Weiqi; Meng, Xia; Li, Hao; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2017-05-16

To investigate the short-term time course risks and benefits of clopidogrel with aspirin in minor ischemic stroke or TIA. Data were derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. The primary outcome was a new ischemic stroke. Safety outcomes included any bleeding and moderate to severe bleeding. Time course analyses were performed for the outcomes of both stroke and bleeding. A total of 145 (71.1%), 13 (6.4%), and 12 (5.9%) of 204 new ischemic strokes in the clopidogrel-aspirin group vs 223 (75.6%), 19 (6.4%), and 8 (2.7%) of 295 in the aspirin alone group occurred at the first, second, and third week, respectively. A total of 23 (38.3%), 15 (25.0%), and 9 (15.0%) of 60 bleeding cases in the clopidogrel-aspirin group vs 15 (36.6%), 8 (19.5%), and 3 (7.3%) of 41 in the aspirin alone group occurred at the first, second, and third week, respectively. Clopidogrel-aspirin treatment numerically reduced the risk of ischemic stroke within the first 2 weeks. From the 10th day, the number of any bleeding cases caused by dual antiplatelets outweighed that of new stroke reduced by dual antiplatelets. Clopidogrel-aspirin treatment may have a benefit of reducing stroke risk outweighing the potential risk of increased bleeding especially within the first 2 weeks compared with aspirin alone in patients with minor stroke or TIA. NCT00979589. This study provides Class II evidence that for patients with minor stroke or TIA, the reduction of stroke risk from clopidogrel plus aspirin within the first 2 weeks outweighs the risk of bleeding compared with aspirin alone. © 2017 American Academy of Neurology.

Population-based study of ischemic stroke risk after trauma in children and young adults.

PubMed

Fox, Christine K; Hills, Nancy K; Vinson, David R; Numis, Adam L; Dicker, Rochelle A; Sidney, Stephen; Fullerton, Heather J

2017-12-05

To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected. © 2017 American Academy of Neurology.

Temporal Trends in Sex Differences With Regard to Stroke Incidence: The Dijon Stroke Registry (1987-2012).

PubMed

Giroud, Marie; Delpont, Benoit; Daubail, Benoit; Blanc, Christelle; Durier, Jérôme; Giroud, Maurice; Béjot, Yannick

2017-04-01

We evaluated temporal trends in stroke incidence between men and women to determine whether changes in the distribution of vascular risk factors have influenced sex differences in stroke epidemiology. Patients with first-ever stroke including ischemic stroke, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, and undetermined stroke between 1987 and 2012 were identified through the population-based registry of Dijon, France. Incidence rates were calculated for age groups, sex, and stroke subtypes. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating incidence rate ratios (IRRs) with Poisson regression. Four thousand six hundred and fourteen patients with a first-ever stroke (53.1% women) were recorded. Incidence was lower in women than in men (112 versus 166 per 100 000/y; IRR, 0.68; P <0.001), especially in age group 45 to 84 years, and for both ischemic stroke and intracerebral hemorrhage. From 1987 to 2012, the lower incidence of overall stroke in women was stable (IRR ranging between 0.63 and 0.72 according to study periods). When considering stroke subtype, a slight increase in the incidence of ischemic stroke was observed in both men (IRR, 1.011; 95% confidence interval, 1.005-1.016; P =0.001) and women (IRR, 1.013; 95% confidence interval, 1.007-1.018; P =0.001). The sex gap in incidence remained unchanged in ischemic stroke and intracerebral hemorrhage. Conversely, the lower subarachnoid hemorrhage incidence in women vanished with time because of an increasing incidence. The sex gap in stroke incidence did not change with time except for subarachnoid hemorrhage. Despite lower rates, more women than men experience an incident stroke each year because of a longer life expectancy. © 2017 American Heart Association, Inc.

Dietary Intake of α-Linolenic Acid Is Not Appreciably Associated with Risk of Ischemic Stroke among Middle-Aged Danish Men and Women.

PubMed

Bork, Christian S; Venø, Stine K; Lundbye-Christensen, Søren; Jakobsen, Marianne U; Tjønneland, Anne; Schmidt, Erik B; Overvad, Kim

2018-06-01

Intake of the plant-derived omega-3 (n-3) fatty acid α-linolenic acid (ALA) may reduce the risk of ischemic stroke. We have investigated the associations between dietary intake of ALA and the risk of ischemic stroke and ischemic stroke subtypes. This was a follow-up study. A total of 57,053 participants aged 50-64 y were enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Intake of ALA was assessed by a validated semiquantitative food frequency questionnaire. Potential incident cases of ischemic stroke were identified in the Danish National Patient Register, validated, and classified into subtypes based on assumed etiology. Statistical analyses were performed via Cox proportional hazard regression with adjustment for established ischemic stroke risk factors. A total of 1859 ischemic stroke cases were identified during a median of 13.5 y of follow-up. In multivariable analyses using restricted cubic splines adjusting for traditional risk factors for ischemic stroke, we observed no clear associations between dietary intake of ALA and the risk of total ischemic stroke or any of its subtypes including ischemic stroke due to large artery atherosclerosis, ischemic stroke due to small-vessel occlusion, and ischemic stroke due to cardio-embolism. Dietary intake of ALA was neither consistently nor appreciably associated with the risk of ischemic stroke or ischemic stroke subtypes among middle-aged Danish men and women. This study was registered at clinicaltrials.gov as NCT03258983.

Effect of a 5-min cold-water immersion recovery on exercise performance in the heat.

PubMed

Peiffer, J J; Abbiss, C R; Watson, G; Nosaka, K; Laursen, P B

2010-05-01

This study examined the effect of a 5-min cold-water immersion (14 degrees C) recovery intervention on repeated cycling performance in the heat. 10 male cyclists performed two bouts of a 25-min constant-paced (254 (22) W) cycling session followed by a 4-km time trial in hot conditions (35 degrees C, 40% relative humidity). The two bouts were separated by either 15 min of seated recovery in the heat (control) or the same condition with 5-min cold-water immersion (5th-10th minute), using a counterbalanced cross-over design (CP(1)TT(1) --> CWI or CON --> CP(2)TT(2)). Rectal temperature was measured immediately before and after both the constant-paced sessions and 4-km timed trials. Cycling economy and Vo(2) were measured during the constant-paced sessions, and the average power output and completion times were recorded for each time trial. Compared with control, rectal temperature was significantly lower (0.5 (0.4) degrees C) in cold-water immersion before CP(2) until the end of the second 4-km timed trial. However, the increase in rectal temperature (0.5 (0.2) degrees C) during CP(2) was not significantly different between conditions. During the second 4-km timed trial, power output was significantly greater in cold-water immersion (327.9 (55.7) W) compared with control (288.0 (58.8) W), leading to a faster completion time in cold-water immersion (6.1 (0.3) min) compared with control (6.4 (0.5) min). Economy and Vo(2) were not influenced by the cold-water immersion recovery intervention. 5-min cold-water immersion recovery significantly lowered rectal temperature and maintained endurance performance during subsequent high-intensity exercise. These data indicate that repeated exercise performance in heat may be improved when a short period of cold-water immersion is applied during the recovery period.

Emergency department arrival times after acute ischemic stroke during the 1990s.

PubMed

Kleindorfer, Dawn O; Broderick, Joseph P; Khoury, Jane; Flaherty, Matthew L; Woo, Daniel; Alwell, Kathleen; Moomaw, Charles J; Pancioli, Arthur; Jauch, Edward; Miller, Rosie; Kissela, Brett M

2007-01-01

Only 8% of ischemic stroke (IS) patients are eligible for rt-PA, and the largest exclusion criterion is delayed time of presentation to the ED. We sought to investigate whether patients are arriving to the ED more quickly in 1999 than in 1993/94 within our large biracial population of 1.3 million. Using ICD-9 codes 430-436, we ascertained all stroke events that presented to a local ED within our population in 7/93-6/94 and again in 1999. Times were recorded as documented in the medical record. There were 1,792 IS patients that presented to an ED in 1993/94 and 1,973 in 1999. The percentage of patients with documented times arriving in under 3 h improved slightly in 1999 (26% vs. 23% in 93/94, P = 0.03), however, the percentage arriving in under 2 h did not. Blacks significantly improved in arrivals under 3 h: 26% in 1999 compared to 17% in 1993/94 (P = 0.01), while whites did not (26% vs. 25%, P = 0.29). In 1999, only 9% of patients arrived from 3-8 h after symptom onset, the large majority of times were either estimated, unknown, or >8 h. We found only marginal improvement in arrival times during the 1990s. In our population, blacks improved in early arrival after symptom onset, while whites did not. Very few patients arrive 3-8 h after onset; therefore expansion of the acute treatment time window to 8 h is unlikely to dramatically affect acute treatment of ischemic stroke.

Tenecteplase versus Alteplase for the Management of Acute Ischemic Stroke in a Low-income Country-Nepal: Cost, Efficacy, and Safety.

PubMed

Nepal, Gaurav; Kharel, Ghanshyam; Ahamad, Shaik Tanveer; Basnet, Babin

2018-02-09

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered, mutant tissue plasminogen activator, is an alternative thrombolytic agent. The economic feasibility of stroke treatment has been a matter of huge debate and discussion thus far. The use of thrombolytics for the management of ischemic stroke has recently begun in Nepal. In low-income countries like Nepal, where the per capita income falls at just $691.7 and 25.2% of the population are under the poverty line, stroke patients cannot meet treatment expenses. Tenecteplase is easily available (for the management of acute coronary syndrome) in tertiary-level hospitals of Nepal and the price quote of tenecteplase ($450) is half the price of alteplase ($1000). In emergency cases, sometimes, the cost of alteplase can be greater than the patient can afford and they can't undergo thrombolysis even after arriving on time. However, evidence exists that supports the use of other alternatives (tenecteplase), which are also effective in the management of acute ischemic stroke. In this article, we examined current evidence for the efficacy and safety of tenecteplase when compared to alteplase. This review will make neurologists in Nepal familiar with the efficacy and safety of tenecteplase in comparison with alteplase since it is common for patients to not be able to afford the expensive alteplase, which makes guideline-based practice impossible some times.

Near-maximal ECG stress testing and coronary artery disease risk factor analysis in Los Angeles City fire fighters.

PubMed

Barnard, R J; Gardner, G W; Diaco, N V; Kattus, A A

1975-11-01

Near-maximal ECG stress testing and coronary artery disease risk factor analysis including blood pressure, serum cholesterol and smoking habits were conducted on a randomly selected group (N=90) of Los Angeles City Fire Fighters ranging in age from 40 to 59 yrs. The data obtained from the fire fighters were compared to data previously reported for a group of Los Angeles insurance underwriters of the same age range. Only 12% of the fire fighters had cholesterol values greater than 260 mg% while 18% of the insurance executives fell into this category. Only 2% of the fire fighters had blood pressure values greater than 160/90 mm Hg while 25% of the insurance executives were hypertensive. Thirty-two percent of the fire fighters were smokers at the time of testing as compared to 26% for the insurance executives. Only one fire fighter had all three risk factors elevated and only five had two risk factors elevated. Forty-seven of the fire fighters had no risk factors elevated. Ten percent of the fire fighters had ischemic stress tests as compared to 8% for the insurance executives. Of the nine fire fighters with ischemic stress tests one was hypertensive, one had elevated serum triglycerides, and three were smokers at the time of testing. Since the fire fighters are a medically-selected population with low risk factors for CHD, the observed incidence of ischemic stress tests is surprising and suggests that ischemic heart disease may be job associated.

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

PubMed

Ye, Xiaoqin; Wei, Xu; Xie, Yanming; Zou, Yihuai; Zhao, Xingquan; Han, Jianhua; Wang, Xinzhi; Ma, Yunzhi; Bi, Qi; Xie, Qingfan; Zhao, Jianjun; Cao, Xiaolan; Chen, Hongxia; Wang, Shizhong; Yan, Rongmei; Han, Zucheng; Yi, Danhui; Wang, Yongyan

2011-10-01

To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

Analysis of the ST-T complex of the electrocardiogram using the Karhunen--Loeve transform: adaptive monitoring and alternans detection

NASA Technical Reports Server (NTRS)

Laguna, P.; Moody, G. B.; Garcia, J.; Goldberger, A. L.; Mark, R. G.

1999-01-01

The Karhunen-Loeve transform (KLT) is applied to study the ventricular repolarisation period as reflected in the ST-T complex of the surface ECG. The KLT coefficients provide a sensitive means of quantitating ST-T shapes. A training set of ST-T complexes is used to derive a set of KLT basis vectors that permits representation of 90% of the signal energy using four KLT coefficients. As a truncated KLT expansion tends to favor representation of the signal over any additive noise, a time series of KLT coefficients obtained from successive ST-T complexes is better suited for representation of both medium-term variations (such as ischemic changes) and short-term variations (such as ST-T alternans) than discrete parameters such as the ST level or other local indices. For analysis of ischemic changes, an adaptive filter is described that can be used to estimate the KLT coefficient, yielding an increase in the signal-to-noise ratio of 10 dB (u = 0.1), with a convergence time of about three beats. A beat spectrum of the unfiltered KLT coefficient series is used for detection of ST-T alterans. These methods are illustrated with examples from the European ST-T Database. About 20% of records revealed quasi-periodic salvos of ischemic ST-T change episodes and another 20% exhibit repetitive, but not clearly periodic patterns of ST-T change episodes. About 5% of ischemic episodes were associated with ST-T alterans.

Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia.

PubMed

Jacob, Matthias; Paul, Oliver; Mehringer, Laurenz; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Kaczmarek, Ingo; Conzen, Peter; Becker, Bernhard F

2009-04-15

Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction. The impact of augmenting a traditional preservation solution with plasma colloid albumin was therefore investigated. Guinea pig hearts underwent cold ischemic storage for 4 hr using Bretschneider's solution (histidine-tryptophan-ketoglutarate [HTK]) without and with augmentation with 1 g% human albumin. After reperfusion, intracoronary adhesion of polymorphonuclear granulocytes, edema formation, left and right heart performance of pressure-to-volume work, and glycocalyx shedding were assessed. Intracoronary retention of leukocytes was doubled in the traditional group (36.4+/-6.6%), whereas it remained at basal values after albumin preservation (23.5+/-2.4%; P<0.05). Addition of albumin to HTK significantly decreased edema formation (wet to dry weight ratio 6.9+/-0.1 vs. 7.2+/-0.2; P<0.05). Although left heart performance was comparable, right heart cardiac output was doubled in hearts having received HTK containing albumin versus HTK alone (94+/-14 vs. 50+/-11 mL/min/g; P<0.05). Glycocalyx shedding was significantly reduced when the hearts were stored under albumin protection. Augmenting HTK with human albumin improves endothelial integrity and heart performance after 4 hr cold ischemia, because of a marked protection of the endothelial glycocalyx. For the prevention of acute and chronic graft failure, the glycocalyx might represent a new target.

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times.

PubMed

Baron, Corey Allan; Kate, Mahesh; Gioia, Laura; Butcher, Kenneth; Emery, Derek; Budde, Matthew; Beaulieu, Christian

2015-08-01

Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke. © 2015 American Heart Association, Inc.

Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective Single-Center Study.

PubMed

Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Yamagami, Hiroshi; Kohara, Nobuo

2018-04-01

Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy. The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]. Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05). A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Delay time between onset of ischemic stroke and hospital arrival.

PubMed

Biller, J; Patrick, J T; Shepard, A; Adams, H P

1993-01-01

Some current experimental protocols for acute ischemic stroke require the initiation of treatment within hours of the onset of stroke symptoms. We prospectively evaluated 30 patients with acute ischemic stroke based on clinical and computed tomography findings. The time between the onset of stroke symptoms and arrival in the emergency room and subsequently on the stroke service was determined. Within 3, 6,12, and 24 h of the onset of stroke symptoms, 16 (53%), 19 (63%), 22 (73%), and 25 (83%) patients had arrived at the emergency room and 0 (0%), 4 (13%), 14 (47%), and 22 (73%) of them on the stroke service, respectively. From the onset of stroke symptoms, the mean arrival time to the emergency room was 24 h (range, 30 min to 144 h) and to the stroke service was 61 h (range, 4-150 h). The mean time between arrival in the emergency room and stroke service was 8.6 h (range, 0-47 h). Even though 53% and 63% of our patients arrived at the emergency room within 3 and 6 h of the onset of stroke symptoms, only 0% and 13% of them arrived on the stroke service within the same time period for the initiation of treatment, respectively. Thus, in order for more patients to qualify for current experimental protocols, they must arrive on the stroke service more quickly or treatment must be initiated in the emergency room. Copyright © 1993. Published by Elsevier Inc.

Quantitative evaluation of the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia in the gerbil: effects of the anesthetics on ischemic depolarization and extracellular glutamate concentration.

PubMed

Kobayashi, Motomu; Takeda, Yoshimasa; Taninishi, Hideki; Takata, Ken; Aoe, Hisami; Morita, Kiyoshi

2007-07-01

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.

Association of ischemic stroke, hormone therapy, and right to left shunt in postmenopausal women.

PubMed

Greep, Nancy C; Liebeskind, David S; Gevorgyan, Rubine; Truong, Tam; Cua, Bennett; Tseng, Chi-Hong; Dodick, David W; Demaerschalk, Bart M; Thaler, David E; Tobis, Jonathan M

2014-09-01

Postmenopausal hormone therapy (HT) increases the risk of venous thrombosis and ischemic stroke. We postulated that HT might increase the risk of ischemic stroke by promoting venous clots that travel to the brain through a right to left shunt (RLS). A total of 2,389 records were studied. After eliminating the premenopausal patients, and those with TIAs and non-ischemic strokes, the medical records of 1846 postmenopausal women hospitalized at four institutions for ischemic stroke were reviewed to identify those who had undergone an adequate study to assess for RLS. The proportion of women with a shunt in users and non-users of HT was compared in stroke patients and in a reference population consisting of postmenopausal women undergoing elective cardiac catheterization. There were 363 (20%) records that had complete data and were included in the analysis. A shunt was more prevalent in patients with a cryptogenic stroke than in patients with a stroke of known cause (55/88 (63%) vs. 53/275 (19%), P < 0.001). In patients with a stroke of known cause, the frequency of a shunt was similar to that in reference women 31/136 (23%), and the proportion of women with a shunt was similar in non-users and current users of HT (14% vs. 20%, P = 0.40). However, among patients with a cryptogenic stroke, the prevalence of a shunt was 1.5 times higher in current users than non-users of HT (82% vs. 56%, P = 0.04). Approximately 23% of older women have a RLS. HT in these women may increase the risk of ischemic stroke by promoting paradoxical embolism. © 2014 Wiley Periodicals, Inc.

Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.

PubMed

Liu, Jie; Jin, Xinchun; Liu, Ke J; Liu, Wenlan

2012-02-29

Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.

Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood brain barrier damage in early ischemic stroke stage

PubMed Central

Liu, Jie; Jin, Xinchun; Liu, Ke J.; Liu, Wenlan

2012-01-01

Blood brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran, and promoted the secretion of metalloproteinase-2 and 9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2-h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis. PMID:22378877

Quantification of image contrast of infarcts on computed tomography scans.

PubMed

Gomolka, R S; Chrzan, R M; Urbanik, A; Kazmierski, R; Grzanka, A D; Nowinski, W L

2017-02-01

Introduction Accurate identification of infarcts in non-contrast computed tomography (NC-CT) scans of the brain is fundamental in the diagnosis and management of patients with stroke. Quantification of image contrast properties at the boundaries of ischemic infarct regions in NC-CT can contribute to a more precise manual or automatic delineation of these regions. Here we explore these properties quantitatively. Methods We retrospectively investigated 519 NC-CT studies of 425 patients with clinically confirmed ischemic strokes. The average and standard deviation (SD) of patients' age was 67.5 ± 12.4 years and the average(median)±SD time from symptoms onset to NC-CT examination was 27.4(12)±35.7 h. For every scan with an ischemic lesion identified by experts, the image contrast of the lesion vs. normal surrounding parenchyma was calculated as a difference of mean Hounsfield Unit (HU) of 1-5 consecutive voxels (the contrast window width) belonging to the lesion and to the parenchyma. This contrast was calculated at each single voxel of ischemic lesion boundaries (previously delineated by the experts) in horizontal and vertical directions in each image. The distributions of obtained horizontal, vertical and both contrasts combined were calculated among all 519 NC-CTs. Results The highest applicative contrast window width was identified as 5 voxels. The ischemic infarcts were found to be characterized by 6.60 HU, 8.28 HU and 7.55 HU mean values for distributions of horizontal, vertical and combined contrasts. Approximately 40-50% of the infarct boundary voxels were found to refer to the image contrast below 5 HU. Conclusion Low image contrast of ischemic lesions prevents accurate delineation of the infarcts in NC-CT.

Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke

PubMed Central

Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A.; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

2016-01-01

In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010–2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006–08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190

Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke.

PubMed

Hsieh, Fang-I; Jeng, Jiann-Shing; Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

2016-01-01

In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010-2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States.

Clinical Outcome of Retinal Vasculitis and Predictors for Prognosis of Ischemic Retinal Vasculitis.

PubMed

Sharief, Lazha; Lightman, Sue; Blum-Hareuveni, Tamar; Bar, Asaf; Tomkins-Netzer, Oren

2017-05-01

To determine factors affecting the visual outcome in eyes with retinal vasculitis and the rate of neovascularization relapse in ischemic vasculitis. Retrospective cohort study. We reviewed 1169 uveitis patients from Moorfields Eye Hospital, London, UK. Retinal vasculitis was observed in 236 eyes (121 ischemic, 115 nonischemic) that were compared with a control group (1022 eyes) with no retinal vasculitis. Ultra-widefield fluorescein angiography images were obtained in 63 eyes with ischemic vasculitis to quantify area of nonperfusion measured as ischemic index. The risk of vision loss was significantly more in the retinal vasculitis compared with the non-vasculitis group (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.24-2.25, P = .001). Retinal vasculitis had twice the risk of macular edema compared to the non-vasculitis group. Macular ischemia increased the risk of vision loss in vasculitis eyes by 4.4 times. The use of systemic prednisolone in eyes with vasculitis was associated with a reduced risk of vision loss (HR 0.36, 95% CI 0.15-0.82, P = .01). Laser photocoagulation was administered in 75 eyes (62.0%), out of which 29 (38.1%) had new vessel relapse and required additional laser treatment. The median ischemic index was 25.8% (interquartile range 10.2%-46%). Ischemia involving ≥2 quadrants was associated with increased risk of new vessel formation (HR 2.7, 95% CI 1.3-5.5, P = .003). Retinal vasculitis is associated with an increased risk of vision loss, mainly secondary to macular ischemia, and has a higher risk of macular edema compared to eyes with no vasculitis. Ischemia involving ≥2 quadrants is a risk factor for new vessel formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

PubMed

Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Benavente, Oscar; Zweifler, Richard M; Callahan, Alfred; Hennerici, Michael G; Zivin, Justin A; Welch, K Michael A

2010-03-01

Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

Cardiovascular, Rheumatologic, and Pharmacologic Predictors of Stroke in Patients With Rheumatoid Arthritis: A Nested, Casee–Control Study

PubMed Central

Nadareishvili, Zurab; Michaud, Kaleb; Hallenbeck, John M.; Wolfe, Frederick

2009-01-01

Objective To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. Methods We performed nested case–control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti–tumor necrosis factor (anti-TNF) treatment effects in RA. Results We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16–2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24–5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97–5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34–1.82]). Conclusion RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain. PMID:18668583

Deciphering the pharmacological mechanism of the Chinese formula Huanglian-Jie-Du decoction in the treatment of ischemic stroke using a systems biology-based strategy

PubMed Central

Zhang, Yan-qiong; Wang, Song-song; Zhu, Wei-liang; Ma, Yan; Zhang, Fang-bo; Liang, Ri-xin; Xu, Hai-yu; Yang, Hong-jun

2015-01-01

Aim: Huanglian-Jie-Du decoction (HLJDD) is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the pharmacological mechanisms of HLJDD in the treatment of ischemic stroke using systems biology approaches. Methods: Putative targets of HLJDD were predicted using MetaDrug. An interaction network of putative HLJDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HLJDD targets were identified by calculating topological features, including 'Degree', 'Node-betweenness', 'Closeness', and 'K-coreness'. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. Results: A total of 809 putative targets were obtained for 168 compositive compounds in HLJDD. Additionally, 39 putative targets were common to all four herbs of HLJDD. Next, 49 major nodes were identified as candidate HLJDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology (GO) annotation system and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HLJDD targets had strong binding efficiencies. Conclusion: This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HLJDD and their putative targets and ischemic stroke-related pathways. PMID:25937634

Association Between Rheumatoid Arthritis and Risk of Ischemic and Nonischemic Heart Failure.

PubMed

Mantel, Ängla; Holmqvist, Marie; Andersson, Daniel C; Lund, Lars H; Askling, Johan

2017-03-14

It is unknown whether the increased risk of heart failure (HF) in rheumatoid arthritis (RA) is independent of ischemic heart disease (IHD). This study sought to investigate the relative risk of HF overall and by subtype (ischemic and nonischemic HF) in patients with RA and to assess the impact of RA disease factors. Two contemporary cohorts of RA subjects were identified from Swedish patient and rheumatology registries and matched 1:10 to general population comparator subjects. A first-ever HF diagnosis (classified as ischemic HF or nonischemic HF based on the presence of IHD) was assessed through registry linkages. Relative risks for a history of HF before RA onset were calculated through odds ratios. Relative risks of incident HF in RA were calculated as hazard ratios (HRs). By the time of RA onset, a history of HF was not more common in RA. In the new-onset RA cohort, the overall HRs for subsequent HF (any type), ischemic HF, and nonischemic HF were between 1.22 and 1.27. The risk of nonischemic HF increased rapidly after RA onset, in contrast to the risk of ischemic HF. High disease activity was associated with all HF types but was most pronounced for nonischemic HF. In the cohort of patients with RA of any duration, the HRs were between 1.71 and 1.88 for the different HF subtypes. Patients with RA are at increased risk of HF that cannot be explained by their increased risk of IHD. The increased risk of nonischemic HF occurred early and was associated with RA severity. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Remote ischemic preconditioning and endothelial function in patients with acute myocardial infarction and primary PCI.

PubMed

Manchurov, Vladimir; Ryazankina, Nadezda; Khmara, Tatyana; Skrypnik, Dmitry; Reztsov, Roman; Vasilieva, Elena; Shpektor, Alexander

2014-07-01

Remote ischemic preconditioning by transient limb ischemia reduces myocardial ischemia-reperfusion injury in patients undergoing percutaneous coronary intervention. The aim of the study we report here was to assess the effect of remote ischemic preconditioning on endothelial function in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. Forty-eight patients with acute myocardial infarction were enrolled. All participants were randomly divided into 2 groups. In Group I (n = 23), remote ischemic preconditioning was performed before primary percutaneous coronary intervention (intermittent arm ischemia-reperfusion through 4 cycles of 5-minute inflation and 5-minute deflation of a blood-pressure cuff to 200 mm Hg). In Group II (n = 25), standard percutaneous coronary intervention without preconditioning was performed. We assessed endothelial function using the flow-mediated dilation test on baseline, then within 1-3 hours after percutaneous coronary intervention, and again on days 2 and 7 after percutaneous coronary intervention. The brachial artery flow-mediated dilation results were significantly higher on the first day after primary percutaneous coronary intervention in the preconditioning group (Group I) than in the control group (Group II) (12.1% vs 0.0%, P = .03, and 11.1% vs 6.3%, P = .016, respectively), and this difference remained on the seventh day (12.3% vs 7.4%, P = .0005, respectively). We demonstrated for the first time that remote ischemic preconditioning before primary percutaneous coronary intervention significantly improves endothelial function in patients with acute myocardial infarction, and this effect remains constant for at least a week. We suppose that the improvement of endothelial function may be one of the possible explanations of the effect of remote ischemic preconditioning. Copyright © 2014 Elsevier Inc. All rights reserved.

Neighborhood socioeconomic deprivation and residential instability: effects on incidence of ischemic heart disease and survival after myocardial infarction.

PubMed

Chaix, Basile; Rosvall, Maria; Merlo, Juan

2007-01-01

Previous literature has shown that neighborhood socioeconomic position influences the risk of ischemic heart disease, but little is known about the mechanisms linking the residential context to ischemic heart disease incidence and mortality. We examined whether neighborhood socioeconomic position and neighborhood residential stability (as a determinant of social interaction patterns) have an influence on ischemic heart disease risk. Moreover, we investigated whether dissimilar contextual influences operate at different stages of the disease process, ie, on incidence, 1-day case-fatality, and long-term survival after acute myocardial infarction (MI). Using a large 27-year longitudinal cohort (baseline: 1 January 1996) defined in the Scania region, Sweden, we estimated multilevel survival models adjusted for individual sociodemographic factors and previous diseases of the persons. After adjustment, multilevel survival models indicated that the incidence of ischemic heart disease increased with neighborhood socioeconomic deprivation but was only weakly associated with neighborhood residential instability (for high vs low residential instability, hazard ratio = 1.2; 95% credible interval = 1.0-1.4). Conversely, beyond effects of individual and contextual socioeconomic circumstances and distance to the hospital, we saw a markedly higher 1-day case-fatality (4.9; 1.8-15) and shorter survival time after MI among individuals still alive 28 days after MI (4.3; 1.2-17) in neighborhoods with a high versus low residential instability. Effects of residential instability on post-MI survival may be mediated by the lower availability of social support in residentially unstable neighborhoods, suggesting a new class of intermediate processes that should be taken into account when investigating contextual influences on ischemic heart disease. Moreover, dissimilar contextual effects may operate at various stages of the disease process (ie, on incidence, case-fatality, and survival after MI).

The role of angiogenesis in damage and recovery from ischemic stroke.

PubMed

Arenillas, Juan F; Sobrino, Tomás; Castillo, José; Dávalos, Antoni

2007-06-01

Ischemic stroke is burdened with a high morbidity and mortality in our society. However, there are few effective and largely available therapies for this devastating disease. In additon to advancing acute reperfusion therapies, there is a need to develop treatments aimed to promote repair and regeneration of brain tissue damaged by ischemia (neurorecovery). Therapeutic angiogenesis and vasculogenesis represent novel approaches of regenerative medicine that may help in the cure of patients with acute ischemic stroke. Translation of our knowledge about these processes from the bench to bedside is still underway. Although angiogenesis (the sprouting of new blood vessels from pre-existing vascular structures) is likely to contribute to neurorepair, the finality of the angiogenic response in acute ischemic stroke has not been fully elucidated. The first therapeutic approach to angiogenesis after ischemic stroke would be the modulation of the endogenous angiogenic response. In this setting, early instauration of physical activity, statins, and peroxisome proliferator-activated receptor-gamma agonists may enhance angiogenesis and neuroregeneration. Gene therapy with vascular growth factors has been successfully tested in patients affected by chronic myocardial and peripheral ischemia. Regarding brain ischemia, experiments in animal models have shown that the effect of these growth factors is critically affected by the dosage, route of delivery, and time of administration in relation to stroke onset. In addition, the optimal angiogenic substance is unknown. Finally, vectors for gene transfer should be further optimized. Therapeutic vasculogenesis consists of the administration of exogenous endothelial progenitor cells in order to enhance brain repair processes. Endothelial progenitor cells may be recruited in response to cerebral ischemia and participate in reparative vasculogenesis after acute ischemic stroke. Further research is needed to clarify their role and therapeutic applicability in human brain ischemia.

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

NASA Astrophysics Data System (ADS)

Rodriguez-Fernandez, P.; White, A. E.; Howard, N. T.; Grierson, B. A.; Staebler, G. M.; Rice, J. E.; Yuan, X.; Cao, N. M.; Creely, A. J.; Greenwald, M. J.; Hubbard, A. E.; Hughes, J. W.; Irby, J. H.; Sciortino, F.

2018-02-01

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.

Cold-Curing Structural Epoxy Resins: Analysis of the Curing Reaction as a Function of Curing Time and Thickness

PubMed Central

Esposito Corcione, Carola; Freuli, Fabrizio; Frigione, Mariaenrica

2014-01-01

The curing reaction of a commercial cold-curing structural epoxy resin, specifically formulated for civil engineering applications, was analyzed by thermal analysis as a function of the curing time and the sample thickness. Original and remarkable results regarding the effects of curing time on the glass transition temperature and on the residual heat of reaction of the cold-cured epoxy were obtained. The influence of the sample thickness on the curing reaction of the cold-cured resin was also deeply investigated. A highly exothermal reaction, based on a self-activated frontal polymerization reaction, was supposed and verified trough a suitable temperature signal acquisition system, specifically realized for this measurement. This is one of the first studies carried out on the curing behavior of these peculiar cold-cured epoxy resins as a function of curing time and thickness. PMID:28788215

Cold-Curing Structural Epoxy Resins: Analysis of the Curing Reaction as a Function of Curing Time and Thickness.

PubMed

Corcione, Carola Esposito; Freuli, Fabrizio; Frigione, Mariaenrica

2014-09-22

The curing reaction of a commercial cold-curing structural epoxy resin, specifically formulated for civil engineering applications, was analyzed by thermal analysis as a function of the curing time and the sample thickness. Original and remarkable results regarding the effects of curing time on the glass transition temperature and on the residual heat of reaction of the cold-cured epoxy were obtained. The influence of the sample thickness on the curing reaction of the cold-cured resin was also deeply investigated. A highly exothermal reaction, based on a self-activated frontal polymerization reaction, was supposed and verified trough a suitable temperature signal acquisition system, specifically realized for this measurement. This is one of the first studies carried out on the curing behavior of these peculiar cold-cured epoxy resins as a function of curing time and thickness.

A randomised controlled trial of coblation, diode laser and cold dissection in paediatric tonsillectomy.

PubMed

Elbadawey, M R; Hegazy, H M; Eltahan, A E; Powell, J

2015-11-01

This study aimed to compare the efficacy of diode laser, coblation and cold dissection tonsillectomy in paediatric patients. A total of 120 patients aged 10-15 years with recurrent tonsillitis were recruited. Participants were prospectively randomised to diode laser, coblation or cold dissection tonsillectomy. Operative time and blood loss were recorded. Pain was recorded on a Wong-Baker FACES(®) pain scale. The operative time (10 ± 0.99 minutes), blood loss (20 ± 0.85 ml) and pain were significantly lower with coblation tonsillectomy than with cold dissection tonsillectomy (20 ± 1.0 minutes and 30 ± 1.0 ml; p = 0.0001) and diode laser tonsillectomy (15 ± 0.83 minutes and 25 ± 0.83 ml; p = 0.0001). Diode laser tonsillectomy had a shorter operative time (p = 0.0001) and less blood loss (p = 0.001) compared with cold dissection tonsillectomy. However, at post-operative day seven, the diode laser tonsillectomy group had significantly higher pain scores compared with the cold dissection (p = 0.042) and coblation (p = 0.04) tonsillectomy groups. Both coblation and diode laser tonsillectomy are associated with significantly reduced blood loss and shorter operative times compared with cold dissection tonsillectomy. However, we advocate coblation tonsillectomy because of the lower post-operative pain scores compared with diode laser and cold dissection tonsillectomy.

Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population.

PubMed

Kim, Joon-Tae; Fonarow, Gregg C; Smith, Eric E; Reeves, Mathew J; Navalkele, Digvijaya D; Grotta, James C; Grau-Sepulveda, Maria V; Hernandez, Adrian F; Peterson, Eric D; Schwamm, Lee H; Saver, Jeffrey L

2017-01-10

Earlier tissue plasminogen activator treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: (1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and (2) the shape of the time-benefit curve through 4.5 hours. We analyzed patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs. Among 65 384 tissue plasminogen activator-treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110-173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61 to 270 minutes, was associated with increased odds of discharge to home (adjusted odds ratio, 1.25; 95% confidence interval, 1.07-1.45), independent ambulation at discharge (adjusted odds ratio, 1.22; 95% confidence interval, 1.03-1.45), and freedom from disability (modified Rankin Scale 0-1) at discharge (adjusted odds ratio, 1.72; 95% confidence interval, 1.21-2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tissue plasminogen activator from onset-to-treatment times of 20 through 270 minutes was mildly nonlinear for discharge to home, with more rapid benefit loss in the first 170 minutes than later, and linear for independent ambulation and in-hospital mortality. Thrombolysis started within the first 60 minutes after onset is associated with best outcomes for patients with acute ischemic stroke, and benefit declined more rapidly early after onset for the ability to be discharged home. These findings support intensive efforts to organize stroke systems of care to improve the timeliness of thrombolytic therapy in acute ischemic stroke. © 2016 American Heart Association, Inc.

Protection of retinal function by sulforaphane following retinal ischemic injury.

PubMed

Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

2015-09-01

Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Late night activity regarding stroke codes: LuNAR strokes.

PubMed

Tafreshi, Gilda; Raman, Rema; Ernstrom, Karin; Rapp, Karen; Meyer, Brett C

2012-08-01

There is diurnal variation for cardiac arrest and sudden cardiac death. Stroke may show a similar pattern. We assessed whether strokes presenting during a particular time of day or night are more likely of vascular etiology. To compare emergency department stroke codes arriving between 22:00 and 8:00 hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine if late night strokes are more likely to be true strokes or warrant acute tissue plasminogen activator evaluations. We reviewed prospectively collected cases in the University of California, San Diego Stroke Team database gathered over a four-year period. Stroke codes at six emergency departments were classified based on arrival time. Those arriving between 22:00 and 8:00 hours were classified as LuNAR stroke codes, the remainder were classified as 'n-LuNAR'. Patients were further classified as intracerebral hemorrhage, acute ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke receiving tissue plasminogen activator, transient ischemic attack, and nonstroke. Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes were compared using Wilcoxon's Rank-sum test. A total of 1607 patients were included in our study, of which, 299 (19%) were LuNAR code strokes. The overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7; P=0·022). There was no overall differences in patient diagnoses between LuNAR and n-LuNAR strokes (P=0·169) or diagnosis of acute ischemic stroke receiving tissue plasminogen activator (n-LuNAR 191 (14·6%), LuNAR 42 (14·0%); P=0·86). Mean arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR 54·9±76·3 min, LuNAR 62·5±87·7 min; P=0·027). There was no significant difference in 90-day mortality (n-LuNAR 15·0%, LuNAR 13·2%; P=0·45). Our stroke center experience showed no difference in diagnosis of acute ischemic stroke between day and night stroke codes. This similarity was further supported in similar rates of tissue plasminogen activator administration. Late night strokes may warrant a more rapid stroke specialist evaluation due to the longer time elapsed from symptom onset and the longer time to computed tomography scan. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Impact of cold climates on vehicle emissions: the cold start air toxics pulse : final report.

DOT National Transportation Integrated Search

2016-09-21

This project measured cold start emissions from four vehicles in winter using fast response instrumentation to accurately measure the : time variation of the cold start emission pulse. Seventeen successful tests were conducted over a temperature rang...

Induction of proliferation of basal epidermal keratinocytes by cold atmospheric-pressure plasma.

PubMed

Hasse, S; Duong Tran, T; Hahn, O; Kindler, S; Metelmann, H-R; von Woedtke, T; Masur, K

2016-03-01

Over the past few decades, new cold plasma sources have been developed that have the great advantage of operating at atmospheric pressure and at temperatures tolerable by biological material. New applications for these have emerged, especially in the field of dermatology. Recently it was demonstrated that cold atmospheric-pressure plasma positively influences healing of chronic wounds. The potential of cold plasma lies in its capacity to reduce bacterial load in the wound while at the same time stimulating skin cells and therefore promoting wound closure. In recent years, there have been great advances in the understanding of the molecular mechanisms triggered by cold plasma involving signalling pathways and gene regulation in cell culture. To investigate cold plasma-induced effects in ex vivo treated human skin biopsies. Human skin tissue was exposed to cold plasma for different lengths of time, and analysed by immunofluorescence with respect to DNA damage, apoptosis, proliferation and differentiation markers. After cold plasma treatment, the epidermal integrity and keratin expression pattern remained unchanged. As expected, the results revealed an increase in apoptotic cells after 3 and 5 min of treatment. Strikingly, an induction of proliferating basal keratinocytes was detected after cold plasma exposure for 1 and 3 min. As these are the cells that regenerate the epidermis, this could indeed be beneficial for wound closure. We investigated the effect of cold plasma on human skin by detecting molecules for growth and apoptosis, and found that both processes are dependent on treatment time. Therefore, this approach offers promising results for further applications of cold plasma in clinical dermatology. © 2015 British Association of Dermatologists.

Reducing time delays in the management of ischemic stroke patients in Northern Italy.

PubMed

Vidale, Simone; Arnaboldi, Marco; Bezzi, Giacomo; Bono, Giorgio; Grampa, Giampiero; Guidotti, Mario; Perrone, Patrizia; Salmaggi, Andrea; Zarcone, Davide; Zoli, Alberto; Agostoni, Elio

2016-07-15

Thrombolysis represents the best therapy for ischemic stroke but the main limitation of its administration is time. The avoidable delay is a concept reflecting the effectiveness of management pathway. For this reason, we projected a study concerning the detection of main delays with following introduction of corrective factors. In this paper we describe the results after these corrections. Consecutive patients admitted for ischemic stroke during a 3-months period to 35 hospitals of a macro-area of Northern Italy were enrolled. Each time of management was registered, identifying three main intervals: pre-hospital, in-hospital and total times. Previous corrective interventions were: 1.increasing of population awareness to use the Emergency Medical Service (EMS); 2.pre-notification of Emergency Department; 3.use of high urgency codes; 4.use of standardised operational algorithm. Statistical analysis was conducted using time-to-event analysis and Cox proportional hazard regression. 1084 patients were enrolled. EMS was alerted for 56.3% of subjects, mainly in females and severe strokes (p<0.001). Thrombolytic treatment was performed in 4.7% of patients. Median pre-hospital and in-hospital times were 113 and 105min, while total time was 240. High urgency codes at transport contributed to reduce pre-hospital and in-hospital time (p<0.05). EMS use and high urgency codes promoted thrombolysis. Treatment within 4.5hours from symptom onset was performed in 14% of patients more than the first phase of study. The implementation of an organizational system based on EMS and concomitant high urgency codes use was effective to reduce avoidable delay and to increase thrombolysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction: the study on gene construction, identification and function].

PubMed

Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo

2008-06-18

To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (P<0.05). These differentially expressed genes represented the proteins which might play important roles in the pathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.

The Relationship between Frontal Lobe Lesions, Course of Post-Stroke Depression, and 1-year Prognosis in Patients with First-Ever Ischemic Stroke

PubMed Central

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S.; Chiu, Helen F. K.; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Background and Purpose Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. Methods A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. Results There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039–3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Conclusions Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction. PMID:25003990

The relationship between frontal lobe lesions, course of post-stroke depression, and 1-year prognosis in patients with first-ever ischemic stroke.

PubMed

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S; Chiu, Helen F K; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039-3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction.

Observation of Solvent Penetration during Cold Denaturation of E. coli Phosphofructokinase-2

PubMed Central

Ramírez-Sarmiento, César A.; Baez, Mauricio; Wilson, Christian A.M.; Babul, Jorge; Komives, Elizabeth A.; Guixé, Victoria

2013-01-01

Phosphofructokinase-2 is a dimeric enzyme that undergoes cold denaturation following a highly cooperative N2 2I mechanism with dimer dissociation and formation of an expanded monomeric intermediate. Here, we use intrinsic fluorescence of a tryptophan located at the dimer interface to show that dimer dissociation occurs slowly, over several hours. We then use hydrogen-deuterium exchange mass spectrometry experiments, performed by taking time points over the cold denaturation process, to measure amide exchange throughout the protein during approach to the cold denatured state. As expected, a peptide corresponding to the dimer interface became more solvent exposed over time at 3°C; unexpectedly, amide exchange increased throughout the protein over time at 3°C. The rate of increase in amide exchange over time at 3°C was the same for each region and equaled the rate of dimer dissociation measured by tryptophan fluorescence, suggesting that dimer dissociation and formation of the cold denatured intermediate occur without appreciable buildup of folded monomer. The observation that throughout the protein amide exchange increases as phosphofructokinase-2 cold denatures provides experimental evidence for theoretical predictions that cold denaturation primarily occurs by solvent penetration into the hydrophobic core of proteins in a sequence-independent manner. PMID:23708365

Observation of solvent penetration during cold denaturation of E. coli phosphofructokinase-2.

PubMed

Ramírez-Sarmiento, César A; Baez, Mauricio; Wilson, Christian A M; Babul, Jorge; Komives, Elizabeth A; Guixé, Victoria

2013-05-21

Phosphofructokinase-2 is a dimeric enzyme that undergoes cold denaturation following a highly cooperative N2 2I mechanism with dimer dissociation and formation of an expanded monomeric intermediate. Here, we use intrinsic fluorescence of a tryptophan located at the dimer interface to show that dimer dissociation occurs slowly, over several hours. We then use hydrogen-deuterium exchange mass spectrometry experiments, performed by taking time points over the cold denaturation process, to measure amide exchange throughout the protein during approach to the cold denatured state. As expected, a peptide corresponding to the dimer interface became more solvent exposed over time at 3°C; unexpectedly, amide exchange increased throughout the protein over time at 3°C. The rate of increase in amide exchange over time at 3°C was the same for each region and equaled the rate of dimer dissociation measured by tryptophan fluorescence, suggesting that dimer dissociation and formation of the cold denatured intermediate occur without appreciable buildup of folded monomer. The observation that throughout the protein amide exchange increases as phosphofructokinase-2 cold denatures provides experimental evidence for theoretical predictions that cold denaturation primarily occurs by solvent penetration into the hydrophobic core of proteins in a sequence-independent manner. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Short-Term Effect of Ambient Temperature on Mortality in Wuhan, China: A Time-Series Study Using a Distributed Lag Non-Linear Model

PubMed Central

Zhang, Yunquan; Li, Cunlu; Feng, Renjie; Zhu, Yaohui; Wu, Kai; Tan, Xiaodong; Ma, Lu

2016-01-01

Less evidence concerning the association between ambient temperature and mortality is available in developing countries/regions, especially inland areas of China, and few previous studies have compared the predictive ability of different temperature indictors (minimum, mean, and maximum temperature) on mortality. We assessed the effects of temperature on daily mortality from 2003 to 2010 in Jiang’an District of Wuhan, the largest city in central China. Quasi-Poisson generalized linear models combined with both non-threshold and double-threshold distributed lag non-linear models (DLNM) were used to examine the associations between different temperature indictors and cause-specific mortality. We found a U-shaped relationship between temperature and mortality in Wuhan. Double-threshold DLNM with mean temperature performed best in predicting temperature-mortality relationship. Cold effect was delayed, whereas hot effect was acute, both of which lasted for several days. For cold effects over lag 0–21 days, a 1 °C decrease in mean temperature below the cold thresholds was associated with a 2.39% (95% CI: 1.71, 3.08) increase in non-accidental mortality, 3.65% (95% CI: 2.62, 4.69) increase in cardiovascular mortality, 3.87% (95% CI: 1.57, 6.22) increase in respiratory mortality, 3.13% (95% CI: 1.88, 4.38) increase in stroke mortality, and 21.57% (95% CI: 12.59, 31.26) increase in ischemic heart disease (IHD) mortality. For hot effects over lag 0–7 days, a 1 °C increase in mean temperature above the hot thresholds was associated with a 25.18% (95% CI: 18.74, 31.96) increase in non-accidental mortality, 34.10% (95% CI: 25.63, 43.16) increase in cardiovascular mortality, 24.27% (95% CI: 7.55, 43.59) increase in respiratory mortality, 59.1% (95% CI: 41.81, 78.5) increase in stroke mortality, and 17.00% (95% CI: 7.91, 26.87) increase in IHD mortality. This study suggested that both low and high temperature were associated with increased mortality in Wuhan, and that mean temperature had better predictive ability than minimum and maximum temperature in the association between temperature and mortality. PMID:27438847

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-07-08

Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus.

PubMed

Hirayama, Koki; Oshima, Hideki; Yamashita, Akiko; Sakatani, Kaoru; Yoshino, Atsuo; Katayama, Yoichi

2016-09-01

We examined the effects of silymarin, which was extracted from Silybum marianum, on delayed neuronal cell death in the rat hippocampus. Rats were divided into four groups: sham-operated rats (sham group), rats which underwent ischemic surgery (control group), rats which were treated with silymarin before and after ischemic surgery (pre group), and rats which were treated with silymarin after ischemic surgery only (post group). We performed the ischemic surgery by occluding the bilateral carotid arteries for 20min and sacrificed the rats one week after the surgery. Silymarin was administered orally at 200mg/kg body weight. Smaller numbers of delayed cell deaths were noted in the rat CA1 region of the pre- and post-groups, and no significant difference was observed between these groups. There were few apoptotic cell deaths in all groups. Compared to the control group, significantly fewer cell deaths by autophagy were found in the pre- and post-group. We concluded that silymarin exerts a preservation effect on delayed neuronal cell death in the rat hippocampus and this effect has nothing to do with the timing of administering of silymarin. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

PubMed Central

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-01-01

Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349

Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold.

PubMed

Machado, Frederico Sander Mansur; Zhang, Zhi; Su, Yan; de Goede, Paul; Jansen, Remi; Foppen, Ewout; Coimbra, Cândido Celso; Kalsbeek, Andries

2018-01-01

Daily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT) and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle. Male Wistar rats were subjected to a single episode of 3 h cold ambient temperature (4°C) at one of 6 time-points starting at Zeitgeber Times 3, 7, 11, 15, 19, and 23. Metabolic rate, core body temperature, locomotor activity (LA), feeding, and drinking behaviors were recorded during control and cold conditions at each time-point. Immediately after the stimulus, rats were euthanized and both the soleus and BAT were collected for real-time PCR. During the light phase (i.e., inactive phase), cold exposure resulted in a slight hyperthermia ( p  < 0.001). Light phase cold exposure also increased metabolic rate and LA ( p  < 0.001). In addition, the prevalence of fat oxidative metabolism was attenuated during the inactive phase ( p  < 0.001). These metabolic changes were accompanied by time-of-day and tissue-specific changes in core clock gene expression, such as DBP ( p  < 0.0001) and REV-ERBα ( p  < 0.01) in the BAT and CLOCK ( p  < 0.05), PER2 ( p  < 0.05), CRY1 ( p  < 0.05), CRY2 ( p  < 0.01), and REV-ERBα ( p  < 0.05) in the soleus skeletal muscle. Moreover, genes involved in substrate oxidation and thermogenesis were affected in a time-of-day and tissue-specific manner by cold exposure. The time-of-day modulation of substrate mobilization and oxidation during cold exposure provides a clear example of the circadian modulation of physiological and metabolic responses. Interestingly, after cold exposure, time-of-day mostly affected circadian clock gene expression in the soleus muscle, despite comparable changes in LA over the light-dark-cycle. The current findings add further evidence for tissue-specific actions of the internal clock in different peripheral organs such as skeletal muscle and BAT.

Seasonal Snow Cold Content Dynamics in the Alpine and Sub-Alpine, Niwot Ridge, Colorado, USA

NASA Astrophysics Data System (ADS)

Jennings, K. S.; Molotch, N. P.

2015-12-01

Cold content represents the energy required to warm a sub-freezing snowpack to an isothermal 0°C. Across daily and seasonal time scales it is a dynamic interplay between the forces of snowpack accumulation/cooling and warming. Cold content determines snowmelt timing and is an important component of the annual energy budget of mountain sites with seasonal snowpacks. However, little is understood about seasonal snowpack cold content dynamics as calculating cold content requires depth-weighted snowpack temperature and snow water equivalent (SWE) measurements, which are scarce. A spatially distributed network of snow pits has been sampled since 1993 at the Niwot Ridge Long Term Ecological Research site on the eastern slope of the Continental Divide in Colorado's Front Range mountains. This study uses data from 3 pit sites that have at least 8 years of observations and represent alpine and sub-alpine environments. For these pits, cold content is strongly related to SWE during the cold content accumulation phase, here defined as December, January, and February. Average peak cold content ranges between -2.5 MJ m-2 and -9.2 MJ m-2 for the three sites and is strongly related to peak SWE. On average, cold content reaches its maximum on February 26, which is 61 days before the average date of peak SWE (i.e., the snowpack's cold content is satisfied over an average of 61 days). At the alpine site, later peak cold content and SWE was observed relative to the lower elevation sub-alpine sites. Interestingly, the alpine site had a smaller gap between peak cold content and SWE (55 days versus 67 days for the alpine and sub-alpine sites, respectively). The gap between peak cold content and peak SWE is primarily a function of the increase in SWE between the two dates. Hence, persistent snowfall after the date of peak cold content can delay the onset of snowmelt even if peak cold content was relatively low. Improving our understanding of seasonal cold content dynamics in mountain environments will enable us to better model the future effects of climate change on snowmelt timing and associated hydrologic response.

Internal Carotid Artery Web as the Cause of Recurrent Cryptogenic Ischemic Stroke.

PubMed

Antigüedad-Muñoz, Jon; de la Riva, Patricia; Arenaza Choperena, Gorka; Muñoz Lopetegi, Amaia; Andrés Marín, Naiara; Fernández-Eulate, Gorka; Moreno Valladares, Manuel; Martínez Zabaleta, Maite

2018-05-01

Carotid artery web is considered an exceptional cause of recurrent ischemic strokes in the affected arterial territory. The underlying pathology proposed for this entity is an atypical fibromuscular dysplasia. We present the case of a 43-year-old woman with no cardiovascular risk factors who had experienced 2 cryptogenic ischemic strokes in the same arterial territory within an 11-month period. Although all diagnostic tests initially yielded normal results, detailed analysis of the computed tomography angiography images revealed a carotid web; catheter angiography subsequently confirmed the diagnosis. Carotid surgery was performed, since which time the patient has remained completely asymptomatic. The histological finding of intimal hyperplasia is consistent with previously reported cases of carotid artery web. Carotid artery web is an infrequent cause of stroke, and this diagnosis requires a high level of suspicion plus a detailed analysis of vascular imaging studies. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Adenosine and Ischemic Preconditioning

PubMed Central

Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

2012-01-01

Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

Effects of a stable prostacyclin analog on experimental ischemic acute renal failure.

PubMed Central

Tobimatsu, M; Ueda, Y; Saito, S; Tsumagari, T; Konomi, K

1988-01-01

The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting. Images Figs. 3A-D. Figs. 4A-D. PMID:3291800

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.

PubMed

Kernan, Walter N; Ovbiagele, Bruce; Black, Henry R; Bravata, Dawn M; Chimowitz, Marc I; Ezekowitz, Michael D; Fang, Margaret C; Fisher, Marc; Furie, Karen L; Heck, Donald V; Johnston, S Claiborne Clay; Kasner, Scott E; Kittner, Steven J; Mitchell, Pamela H; Rich, Michael W; Richardson, DeJuran; Schwamm, Lee H; Wilson, John A

2014-07-01

The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines. © 2014 American Heart Association, Inc.

Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

PubMed Central

Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

2007-01-01

The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology. PMID:17971868

Living within stories: Exploring the experiences of people with transient ischemic attack.

PubMed

Crowfoot, Gary Mitchell; van der Riet, Pamela Jane; Maguire, Jane Margaret

2016-03-01

A transient ischemic attack (TIA) significantly increases a person's risk of ischemic stroke. However, little is known about the experiences of these people or what influences their decision to access care. This article explores the stories of three people who experienced a TIA. All participants were interviewed after receiving a diagnosis of TIA by a specialist neurologist. By utilizing a framework of narrative inquiry, several storylines were revealed across temporal, social, and geographical landscapes. The main storylines include: bodily disruption, time stasis, altered temporal perceptions, the roles of others, and help-seeking behavior. The primary author also reflects upon his own origin and explores how this inquiry has influenced his perceptions, career, and nursing practice. This inquiry may assist healthcare workers to gain insight into the experiences of people with TIA and suggests how involvement of significant others is beneficial when educating people at risk of TIA. © 2015 Wiley Publishing Asia Pty Ltd.

Interactions between Age, Sex, and Hormones in Experimental Ischemic Stroke

PubMed Central

Liu, Fudong; McCullough, Louise D.

2012-01-01

Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations versus effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed. PMID:23068990

Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis.

PubMed

Zhou, Xin; Patel, Darshan; Sen, Sabyasachi; Shanmugam, Victoria; Sidawy, Anton; Mishra, Lopa; Nguyen, Bao-Ngoc

2017-04-01

Chronic nonhealing wounds are a major health problem for patients in the United States and worldwide. Diabetes and ischemia are two major risk factors behind impaired healing of chronic lower extremity wounds. Poly-ADP-ribose polymerase (PARP) is found to be overactivated with both ischemic and diabetic conditions. This study seeks a better understanding of the role of PARP in ischemic and diabetic wound healing, with a specific focus on angiogenesis and vasculogenesis. Ischemic and diabetic wounds were created in FVB/NJ mice and an in vitro scratch wound model. PARP inhibitor PJ34 was delivered to the animals at 10 mg/kg/d through implanted osmotic pumps or added to the culture medium, respectively. Animal wound healing was assessed by daily digital photographs. Animal wound tissues, peripheral blood, and bone marrow cells were collected at different time points for further analysis with Western blot and flow cytometry. Scratch wound migration and invasion angiogenesis assays were performed using human umbilical vein endothelial cells (HUVECs). Measurements were reported as mean ± standard deviation. Continuous measurements were compared by t-test. P < .05 was considered statistically significant. A significant increase in PARP activity was observed under ischemic and diabetic conditions that correlated with delayed wound healing and slower HUVEC migration. The beneficial effect of PARP inhibition with PJ34 on ischemic and diabetic wound healing was observed in both animal and in vitro models. In the animal model, the percentage of wound healing was significantly enhanced from 43% ± 6% to 71% ± 9% (P < .05) by day 7 with the addition of PJ34. PARP inhibition promoted angiogenesis at the ischemic and diabetic wound beds as evidenced by significantly higher levels of endothelial cell markers (vascular endothelial growth factor receptor 2 [VEGFR2] and endothelial nitric oxide synthase) in mice treated with PJ34 compared with controls. Flow cytometry analysis of peripheral blood mononuclear cells showed that PARP inhibition increased mobilization of endothelial progenitor cells (VEGFR2 + /CD133 + and VEGFR2 + /CD34 + ) into the systemic circulation. Furthermore, under in vitro hyperglycemia and hypoxia conditions, PARP inhibition enhanced HUVEC migration and invasion in Boyden chamber assays by 80% and 180% (P < .05), respectively. Delayed healing in ischemic and diabetic wounds is caused by PARP hyperactivity, and PARP inhibition significantly enhanced ischemic and diabetic wound healing by promoting angiogenesis. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

PubMed

Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

2016-10-01

Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm 3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

Male unemployment and cause-specific mortality in postwar Scotland.

PubMed

Forbes, J F; McGregor, A

1987-01-01

This article reports a time-series analysis of male unemployment and mortality in postwar Scotland. The results provide little evidence to support the hypothesis that unemployment exerts a significant and consistent positive impact on mortality from all causes, lung cancer, ischemic heart disease, and cerebrovascular disease. Although significant positive associations between unemployment and mortality from lung cancer and ischemic heart disease were detected for older males in the short term, the long-term association between unemployment and mortality tends to be negative. Further progress on establishing possible causal relationships between unemployment and health requires both the collaboration of medical and social scientists and a well designed prospective study that avoids many of the problems associated with time-series and cross-sectional analyses.

Angiogenesis-regulating microRNAs and ischemic stroke

PubMed Central

Yin, Ke-Jie; Hamblin, Milton; Chen, Y. Eugene

2014-01-01

Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID:26156265

Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke.

PubMed

Tutwiler, Valerie; Peshkova, Alina D; Andrianova, Izabella A; Khasanova, Dina R; Weisel, John W; Litvinov, Rustem I

2017-02-01

Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro. The main finding is that clot contraction from the blood of stroke patients was reduced compared with healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis, and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke pathogenesis suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke. The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction need further exploration. © 2016 American Heart Association, Inc.

Contraction of Blood Clots is Impaired in Acute Ischemic Stroke

PubMed Central

Tutwiler, Valerie; Peshkova, Alina D.; Andrianova, Izabella A.; Khasanova, Dina R.; Weisel, John W.; Litvinov, Rustem I.

2016-01-01

Objective Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. Approach and Results We employed a novel automated method that enabled us to quantify time of initiation, extent and rate of clot contraction in vitro. The main finding is clot contraction from the blood of stroke patients was reduced compared to healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke etiology suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke. Conclusions The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction needs further exploration. PMID:27908894

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Therapeutic inertia in the outpatient management of dyslipidemia in patients with ischemic heart disease. The inertia study.

PubMed

Lázaro, Pablo; Murga, Nekane; Aguilar, Dolores; Hernández-Presa, Miguel A

2010-12-01

Studies indicate that dyslipidemia is undertreated. Numerous systematic reviews have shown that, even when therapeutic targets set by clinical practice guidelines have not been met, treatment remains unchanged despite the availability of alternatives approaches. The result is increased morbidity and mortality. Our aims were to investigate this phenomenon, known as therapeutic inertia, in patients with dyslipidemia and ischemic heart disease, and to determine its possible causes. national, multicenter, observational study of data obtained from physicians by questionnaire and from the clinical records of patients with ischemic heart disease. Main variable: therapeutic inertia during a consultation, defined as treatment remaining the same despite a change being indicated (e.g. low-density lipoprotein cholesterol >100 mg/dl or >70 mg/dl in diabetics). Covariates: physician, patient and consultation characteristics. multivariate logistic regression analysis of factors associated with therapeutic inertia during a consultation. Overall, 43% of consultations involved therapeutic inertia, and an association with coronary risk factors, including diabetes, did not result in a change in treatment. Therapeutic inertia occurred more frequently when there was a long time between the diagnosis and treatment of dyslipidemia and that of ischemic heart disease. Undertreatment was particularly common in women despite a greater overall risk. The more experienced physicians treated younger patients more appropriately. Clinical practice was improved by educational sessions at conferences. Therapeutic inertia was common in patients with chronic ischemic heart disease and dyslipidemia, irrespective of overall cardiovascular risk. Factors associated with the patient, disease and physician had an influence.

Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

PubMed

Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

2016-05-15

Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

African American women have poor long-term survival following ischemic stroke.

PubMed

Qureshi, Adnan I; Suri, M Fareed K; Zhou, Jingying; Divani, Afshin A

2006-11-14

To determine racial and gender differences in long-term survival following ischemic stroke in a well-defined cohort of patients. We analyzed the prospectively collected data from a randomized, placebo-controlled trial in patients with ischemic stroke presenting within 3 hours of symptom onset. We determined the effect of race and gender on 1-year survival ascertained by serial follow-ups using Kaplan-Meier analysis. Multivariate analysis was performed adjusting for age, initial NIH Stroke Scale (NIHSS) score, use of thrombolysis, time to randomization, stroke etiology, and other cardiovascular risk factors. Of the 547 patients with ischemic stroke, the 1-year survival (percentage +/- SE) for African American women (63 +/- 6%) was lower than white women (73 +/- 4%), African American men (79 +/- 4%), and white men (75 +/- 3%). Among the 209 patients younger than 65 years, the 1-year survival was prominently lower for African American women (66 +/- 8%) vs white women (87 +/- 5%), African American men (83 +/- 5%), and white men (89 +/- 3%). In the Cox proportional hazard analysis, African American women had a significantly higher rate of 1-year mortality (relative risk 2.1, 95% CI 1.2 to 3.5) after adjusting for all potential confounders except diabetes mellitus. After adjustment for diabetes mellitus, the difference became insignificant, although a 70% greater risk of 1-year mortality was still observed. Compared with whites and men, African American women have a lower 1-year survival following ischemic stroke.

Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study.

PubMed

Gioia, Laura C; Kate, Mahesh; Sivakumar, Leka; Hussain, Dulara; Kalashyan, Hayrapet; Buck, Brian; Bussiere, Miguel; Jeerakathil, Thomas; Shuaib, Ashfaq; Emery, Derek; Butcher, Ken

2016-07-01

Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT. © 2016 American Heart Association, Inc.

Outcomes Using Grafts from Donors after Cardiac Death.

PubMed

Doyle, M B Majella; Collins, Kelly; Vachharajani, Neeta; Lowell, Jeffrey A; Shenoy, Surendra; Nalbantoglu, Ilke; Byrnes, Kathleen; Garonzik-Wang, Jacqueline; Wellen, Jason; Lin, Yiing; Chapman, William C

2015-07-01

Previous reports suggest that donation after cardiac death (DCD) liver grafts have increased primary nonfunction (PNF) and cholangiopathy thought to be due to the graft warm ischemia before cold flushing. In this single-center, retrospective study, 866 adult liver transplantations were performed at our institution from January 2005 to August 2014. Forty-nine (5.7%) patients received DCD donor grafts. The 49 DCD graft recipients were compared with all recipients of donation after brain death donor (DBD) grafts and to a donor and recipient age- and size-matched cohort. The DCD donors were younger (age 28, range 8 to 60 years) than non-DCD (age 44.3, range 9 to 80 years) (p < 0.0001), with similar recipient age. The mean laboratory Model for End-Stage Liver Disease (MELD) was lower in DCD recipients (18.7 vs 22.2, p = 0.03). Mean cold and warm ischemia times were similar. Median ICU and hospital stay were 2 days and 7.5 days in both groups (p = 0.37). Median follow-ups were 4.0 and 3.4 years, respectively. Long-term outcomes were similar between groups, with similar 1-, 3- and 5-year patient and graft survivals (p = 0.59). Four (8.5%) recipients developed ischemic cholangiopathy (IC) at 2, 3, 6, and 8 months. Primary nonfunction and hepatic artery thrombosis did not occur in any patient in the DCD group. Acute kidney injury was more common with DCD grafts (16.3% of DCD recipients required dialysis vs 4.1% of DBD recipients, p = 0.01). An increased donor age (>40 years) was shown to increase the risk of IC (p = 0.006). Careful selection of DCD donors can provide suitable donors, with results of liver transplantation comparable to those with standard brain dead donors. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Heat strain in cold.

PubMed

Rintamäki, Hannu; Rissanen, Sirkka

2006-07-01

In spite of increased environmental cold stress, heat strain is possible also in a cold environment. The body heat balance depends on three factors: environmental thermal conditions, metabolic heat production and thermal insulation of clothing and other protective garments. As physical exercise may increase metabolic heat production from rest values by ten times or even more, the required thermal insulation of clothing may vary accordingly. However, in most outdoor work, and often in indoor cold work, too, the thermal insulation of clothing is impractical, difficult or impossible to adjust according to the changes in physical activity. This is especially true with whole body covering garments like chemical protective clothing. As a result of this imbalance, heat strain may develop. In cold all the signs of heat strain (core temperature above 38 degrees C, warm or hot thermal sensations, increased cutaneous circulation and sweating) may not be present at the same time. Heat strain in cold may be whole body heat strain or related only to torso or core temperature. Together with heat strain in torso or body core, there can be at the same time even cold strain in peripheral parts and/or superficial layers of the body. In cold environment both the preservation of insulation and facilitation of heat loss are important. Development of clothing design is still needed to allow easy adjustments of thermal insulation.

Pre-cooling with ice slurry ingestion leads to similar run times to exhaustion in the heat as cold water immersion.

PubMed

Siegel, Rodney; Maté, Joseph; Watson, Greig; Nosaka, Kazunori; Laursen, Paul B

2012-01-01

The purpose of this study was to compare the effects of pre-exercise ice slurry ingestion and cold water immersion on submaximal running time in the heat. On three separate occasions, eight males ran to exhaustion at their first ventilatory threshold in the heat (34.0 ± 0.1 ° C, 52 ± 3% relative humidity) following one of three 30 min pre-exercise manoeuvres: (1) ice slurry ingestion; (2) cold water immersion; or (3) warm fluid ingestion (control). Running time was longer following cold water immersion (56.8 ± 5.6 min; P = 0.008) and ice slurry ingestion (52.7 ± 8.4 min; P = 0.005) compared with control (46.7 ± 7.2 min), but not significantly different between cold water immersion and ice slurry ingestion (P = 0.335). During exercise, rectal temperature was lower with cold water immersion from 15 and 20 min into exercise compared with control and ice slurry ingestion, respectively, and remained lower until 40 min (P = 0.001). At exhaustion rectal temperature was significantly higher following ice slurry ingestion (39.76 ± 0.36 ° C) compared with control (39.48 ± 0.36 ° C; P = 0.042) and tended to be higher than cold water immersion (39.48 ± 0.34 ° C; P = 0.065). As run times were similar between conditions, ice slurry ingestion may be a comparable form of pre-cooling to cold water immersion.

Extravasation into brain and subsequent spread beyond the ischemic core of a magnetic resonance contrast agent following a step-down infusion protocol in acute cerebral ischemia

PubMed Central

2014-01-01

Background Limiting expansion of the ischemic core lesion by reinstating blood flow and protecting the penumbral cells is a priority in acute stroke treatment. However, at present, methods are not available for effective drug delivery to the ischemic penumbra. To address these issues this study compared the extravasation and subsequent interstitial spread of a magnetic resonance contrast agent (MRCA) beyond the ischemic core into the surrounding brain in a rat model of ischemia-reperfusion for bolus injection and step-down infusion (SDI) protocols. Methods Male Wistar rats underwent middle cerebral artery (MCA) occlusion for 3 h followed by reperfusion. Perfusion-diffusion mismatched regions indicating the extent of spread were identified by measuring cerebral blood flow (CBF) deficits by arterial spin-labeled magnetic resonance imaging and the extent of the ischemic core by mapping the apparent diffusion coefficient (ADC) of water with diffusion-weighted imaging. Vascular injury was assessed via MRCA, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) penetration, by Look-Locker T1-weighted MR imaging after either a bolus injection (n = 8) or SDI (n = 6). Spatial and temporal expansion of the MRCA front during a 25 min imaging period was measured from images obtained at 2.5 min intervals. Results The mean ADC lesion was 20 ± 7% of the hemispheric area whereas the CBF deficit area was 60 ± 16%, with the difference between the areas suggesting the possible presence of a penumbra. The bolus injection led to MRCA enhancement with an area that initially spread into the ischemic core and then diminished over time. The SDI produced a gradual increase in the area of MRCA enhancement that slowly enlarged to occupy the core, eventually expanded beyond it into the surrounding tissue and then plateaued. The integrated area from SDI extravasation was significantly larger than that for the bolus (p = 0.03). The total number of pixels covered by the SDI at its maximum was significantly larger than the pixels covered by bolus maximum (p = 0.05). Conclusions These results demonstrate that the SDI protocol resulted in a spread of the MRCA beyond the ischemic core. Whether plasma-borne acute stroke therapeutics can be delivered to the ischemic penumbra in a similar way needs to be investigated. PMID:25276343

Extravasation into brain and subsequent spread beyond the ischemic core of a magnetic resonance contrast agent following a step-down infusion protocol in acute cerebral ischemia.

PubMed

Nagaraja, Tavarekere N; Keenan, Kelly A; Aryal, Madhava P; Ewing, James R; Gopinath, Saarang; Nadig, Varun S; Shashikumar, Sukruth; Knight, Robert A

2014-01-01

Limiting expansion of the ischemic core lesion by reinstating blood flow and protecting the penumbral cells is a priority in acute stroke treatment. However, at present, methods are not available for effective drug delivery to the ischemic penumbra. To address these issues this study compared the extravasation and subsequent interstitial spread of a magnetic resonance contrast agent (MRCA) beyond the ischemic core into the surrounding brain in a rat model of ischemia-reperfusion for bolus injection and step-down infusion (SDI) protocols. Male Wistar rats underwent middle cerebral artery (MCA) occlusion for 3 h followed by reperfusion. Perfusion-diffusion mismatched regions indicating the extent of spread were identified by measuring cerebral blood flow (CBF) deficits by arterial spin-labeled magnetic resonance imaging and the extent of the ischemic core by mapping the apparent diffusion coefficient (ADC) of water with diffusion-weighted imaging. Vascular injury was assessed via MRCA, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) penetration, by Look-Locker T1-weighted MR imaging after either a bolus injection (n = 8) or SDI (n = 6). Spatial and temporal expansion of the MRCA front during a 25 min imaging period was measured from images obtained at 2.5 min intervals. The mean ADC lesion was 20 ± 7% of the hemispheric area whereas the CBF deficit area was 60 ± 16%, with the difference between the areas suggesting the possible presence of a penumbra. The bolus injection led to MRCA enhancement with an area that initially spread into the ischemic core and then diminished over time. The SDI produced a gradual increase in the area of MRCA enhancement that slowly enlarged to occupy the core, eventually expanded beyond it into the surrounding tissue and then plateaued. The integrated area from SDI extravasation was significantly larger than that for the bolus (p = 0.03). The total number of pixels covered by the SDI at its maximum was significantly larger than the pixels covered by bolus maximum (p = 0.05). These results demonstrate that the SDI protocol resulted in a spread of the MRCA beyond the ischemic core. Whether plasma-borne acute stroke therapeutics can be delivered to the ischemic penumbra in a similar way needs to be investigated.

Physiological responses and manual performance in humans following repeated exposure to severe cold at night.

PubMed

Ozaki, H; Nagai, Y; Tochihara, Y

2001-04-01

We evaluated human physiological responses and the performance of manual tasks during exposure to severe cold (-25 degrees C) at night (0300-0500 hours) and in the afternoon (1500-1700 hours). Thirteen male students wearing standard cold protective clothing occupied a severely cold room (-25 degrees C) for 20 min, and were then transferred to a cool room (10 degrees C) for 20 min. This pattern of exposure was repeated three times, for a total time of exposure to extreme cold of 60 min. The experiments were started either at 1500 hours or 0300 hours and measurements of rectal temperature, skin temperature, blood pressure, performance in a counting task, hand tremor, and subjective responses were made in each condition. At the end of the experiment at night the mean decrease in rectal temperature [0.68 (SEM 0.04) degree C] was significantly greater than that at the end of the experiment in the afternoon [0.55 (SEM 0.08) degree C, P < 0.01]. After the second cold exposure at night the mean increase in diastolic blood pressure [90 (SEM 2.0) mmHg] was significantly greater than that at the end of the second cold exposure in the afternoon [82 (SEM 2.8) mmHg, P < 0.01]. At the end of the second cold exposure at night, mean finger skin temperature [11.8 (SEM 0.8) degrees C] was significantly higher than that at the comparable time in the afternoon [9.0 (SEM 0.7) degrees C, P < 0.01]. Similarly for the toe, mean skin temperature at the start of the second cold exposure at night [25.6 (SEM 1.5) degrees C] was significantly higher than in the afternoon [20.1 (SEM 0.8) degrees C, P < 0.01]. The increased skin temperatures in the periphery resulted in increased heat loss. Since peripheral skin temperatures were highest at night, the subjects noted diminished sensations of thermal cold and pain at that time. Manual dexterity at the end of the first cold exposure at night [mean 83.7 (SEM 3.6) times.min-1] had decreased significantly more than at the end of the first cold exposure in the afternoon [mean 89.4 (SEM 3.5) times.min-1, P < 0.01]. These findings of a lowered rectal temperature and diminished manual dexterity suggest that there is an increased risk of both hypothermia and accidents for those who work at night.

Time and diffusion lesion size in major anterior circulation ischemic strokes.

PubMed

Hakimelahi, Reza; Vachha, Behroze A; Copen, William A; Papini, Giacomo D E; He, Julian; Higazi, Mahmoud M; Lev, Michael H; Schaefer, Pamela W; Yoo, Albert J; Schwamm, Lee H; González, R Gilberto

2014-10-01

Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows. © 2014 American Heart Association, Inc.

Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury.

PubMed

Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Lee, Jae-Chul; Won, Moo-Ho; Kang, Il-Jun

2013-07-15

Synaptic plasticity is important for functional recovery after cerebral ischemic injury. In the present study, we investigated chronological change in the immunoreactivity of PSD-95, a kind of postsynaptic density protein, in the hippocampus proper (CA1-3 regions) after 5 min of transient cerebral ischemia in gerbils. PSD-95 immunoreactivity was observed in MAP-2-immunoreactive dendrites in the CA1-3 regions of the sham group. The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. However, PSD-95 immunoreactivity began to be dramatically decreased in MAP-2-immunoreactive dendrites in the CA1 region, not CA2-3 region, at early time after ischemia-reperfusion. At 5 days after ischemia-reperfusion, MAP-2 immunoreactivity almost disappeared in the ischemic CA1 region, and PSD-95 immunoreactivity was much lower than that in the sham group. In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic plasticity in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study.

PubMed

O'Brien, Emily C; Greiner, Melissa A; Xian, Ying; Fonarow, Gregg C; Olson, DaiWai M; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Peterson, Eric D; Pencina, Michael J; Hernandez, Adrian F

2015-10-13

In patients with ischemic stroke, data on the real-world effectiveness of statin therapy for clinical and patient-centered outcomes are needed to better inform shared decision making. Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient-Centered Outcomes Research Institute-funded research program designed with stroke survivors to evaluate the effectiveness of poststroke therapies. We linked data on patients ≥65 years of age enrolled in the Get With The Guidelines-Stroke Registry to Medicare claims. Two-year to postdischarge outcomes of those discharged on a statin versus not on a statin were adjusted through inverse probability weighting. Our coprimary outcomes were major adverse cardiovascular events and home time (days alive and out of a hospital or skilled nursing facility). Secondary outcomes included all-cause mortality, all-cause readmission, cardiovascular readmission, and hemorrhagic stroke. From 2007 to 2011, 77 468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard of major adverse cardiovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87-0.94), 28 more home-time days after discharge (P<0.001), and lower all-cause mortality and readmission. Statin therapy at discharge was not associated with increased risk of hemorrhagic stroke (hazard ratio, 0.94; 95% confidence interval, 0.72-1.23). Among statin-treated patients, 31% received a high-intensity dose; after risk adjustment, these patients had outcomes similar to those of recipients of moderate-intensity statin. In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of major adverse cardiovascular events and nearly 1 month more home time during the 2-year period after hospitalization. © 2015 American Heart Association, Inc.

Nonfreezing Cold-Induced Injuries

DTIC Science & Technology

2011-01-01

ty in both m i fitary and civilians who work ill cold conditions. Consequently recognition of those at risk , limiting their exposure and the...shown to have a higher risk for local cold injuries when exposed to cold in real life [10]. Felicijan et al found evidence for a significant...in cold conditions. Consequently recognition of those at risk , limiting their exposure and the appropriate and timely use of suitable protective

Anaesthetic injection versus ischemic compression for the pain relief of abdominal wall trigger points in women with chronic pelvic pain.

PubMed

Montenegro, Mary L L S; Braz, Carolina A; Rosa-e-Silva, Julio C; Candido-dos-Reis, Francisco J; Nogueira, Antonio A; Poli-Neto, Omero B

2015-12-01

Chronic pelvic pain is a common condition among women, and 10 to 30 % of causes originate from the abdominal wall, and are associated with trigger points. Although little is known about their pathophysiology, variable methods have been practiced clinically. The purpose of this study was to evaluate the efficacy of local anaesthetic injections versus ischemic compression via physical therapy for pain relief of abdominal wall trigger points in women with chronic pelvic pain. We conducted a parallel group randomized trial including 30 women with chronic pelvic pain with abdominal wall trigger points. Subjects were randomly assigned to one of two intervention groups. One group received an injection of 2 mL 0.5 % lidocaine without a vasoconstrictor into a trigger point. In the other group, ischemic compression via physical therapy was administered at the trigger points three times, with each session lasting for 60 s, and a rest period of 30 s between applications. Both treatments were administered during one weekly session for four weeks. Our primary outcomes were satisfactory clinical response rates and percentages of pain relief. Our secondary outcomes are pain threshold and tolerance at the trigger points. All subjects were evaluated at baseline and 1, 4, and 12 weeks after the interventions. The study was conducted at a tertiary hospital that was associated with a university providing assistance predominantly to working class women who were treated by the public health system. Clinical response rates and pain relief were significantly better at 1, 4, and 12 weeks for those receiving local anaesthetic injections than ischemic compression via physical therapy. The pain relief of women treated with local anaesthetic injections progressively improved at 1, 4, and 12 weeks after intervention. In contrast, women treated with ischemic compression did not show considerable changes in pain relief after intervention. In the local anaesthetic injection group, pain threshold and tolerance improved with time in the absence of significant differences between groups. Lidocaine injection seems to be better for reducing the severity of chronic pelvic pain secondary to abdominal wall trigger points compared to ischemic compression via physical therapy. ClinicalTrials.gov NCT00628355. Date of registration: February 25, 2008.

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

PubMed

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (p<0.05). Following reperfusion, lesion volumes on the ADC maps significantly reduced but no change was observed on DWI. Visually determined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy.

PubMed

Kim, Hyun Ah; Rhim, Taiyoun; Lee, Minhyung

2011-07-18

Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Magnetic Particle Imaging for Real-Time Perfusion Imaging in Acute Stroke.

PubMed

Ludewig, Peter; Gdaniec, Nadine; Sedlacik, Jan; Forkert, Nils D; Szwargulski, Patryk; Graeser, Matthias; Adam, Gerhard; Kaul, Michael G; Krishnan, Kannan M; Ferguson, R Matthew; Khandhar, Amit P; Walczak, Piotr; Fiehler, Jens; Thomalla, Götz; Gerloff, Christian; Knopp, Tobias; Magnus, Tim

2017-10-24

The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.

Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.

PubMed

Zhao, Junliang; Zhang, Shaohong; Yang, Tifeng; Zeng, Zichong; Huang, Zhanghui; Liu, Qing; Wang, Xiaofei; Leach, Jan; Leung, Hei; Liu, Bin

2015-07-01

Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype. © 2014 Scandinavian Plant Physiology Society.

Age-related reduction of cerebral ischemic preconditioning: myth or reality?

PubMed Central

Della-Morte, David; Cacciatore, Francesco; Salsano, Elisa; Pirozzi, Gilda; Genio, Maria Teresa Del; D’Antonio, Iole; Gargiulo, Gaetano; Palmirotta, Raffaele; Guadagni, Fiorella; Rundek, Tatjana; Abete, Pasquale

2013-01-01

Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed. PMID:24204128

Enterocolic lymphocytic phlebitis: statistical analysis of histology features in viable and ischemic bowel.

PubMed

Medlicott, Shaun A C; Guggisberg, Kelly A; DesCôteaux, Jean-Gaston; Beck, Paul

2006-07-01

Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Myointimal hyperplasia may represent a chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600 submucosal and subserosal veins from both ischemic and intact bowel segments to discern if vascular morphology varied between sites. Crescentic and circumferential lymphocytic phlebitis is more common in viable bowel than in the ischemic segment. A nonsignificant trend was found for increased crescentic morphology between intact bowel remote from the ischemic focus compared with that adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly different in viable and ischemic bowel, changing from the classic lymphocytic to necrotizing lesions respectively.

Non-high-density lipoprotein cholesterol on the risks of stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Zhou, Yong; Wang, Chunxue; Wang, Anxin; Zhang, Qian; Gao, Xiang; Hu, Haitao; Wu, Shouling; Zhao, Xingquan

2013-01-01

To prospectively explore the association between non-high-density lipoprotein cholesterol (non-HDLC) and the risks of stroke and its subtypes. A total of 95,916 participants (18-98 years old; 76,354 men and 19,562 women) from a Chinese urban community who were free of myocardial infarction and stroke at baseline time point (2006-2007) were eligible and enrolled in the study. The serum non-HDLC levels of participants were determined by subtracting the high-density lipoprotein cholesterol (HDLC) from total serum cholesterol. The primary outcome was the first occurrence of stroke, which was diagnosed according to the World Health Organization criteria and classified into three subtypes: ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The Cox proportional hazards models were used to estimate risk of stroke and its subtypes. During the four-year follow-up, we identified 1614 stroke events (1,156 ischemic, 416 intracerebral hemorrhagic and 42 subarachnoid hemorrhagic). Statistical analyses showed that hazard ratios (HR) (95% Confidence Interval: CI) of serum Non-HDLC level for total and subtypes of stroke were: 1.08 (1.03-1.12) (total), 1.10 (1.05-1.16) (ischemic), 1.03 (0.96-1.10) (intracerebral hemorrhage) and 0.83 (0.66-1.05) (subarachnoid hemorrhage). HR for non-HDLC refers to the increase per each 20 mg/dl. For total and ischemic stroke, the risks were significantly higher in the fourth and fifth quintiles of non-HDLC concentrations compared to the first quintile after adjusting the confounding factors (total stroke: 4(th) quintile HR=1.33 (1.12-1.59); 5(th) quintile HR = 1.36 (1.15-1.62); ischemic stroke: 4(th) quintile HR =1.34 (1.09-1.66); 5(th) quintile HR = 1.53 (1.24-1.88)). Our data suggest that serum non-HDLC level is an independent risk factor for total and ischemic stroke, and that higher serum non-HDLC concentrations are associated with increased risks for total stroke and ischemic stroke, but not for intracerebral and subarachnoid hemorrhage.

Integrated quadruple stress echocardiography.

PubMed

Picano, Eugenio; Morrone, Doralisa; Scali, Maria C; Huqi, Alda; Coviello, Katia; Ciampi, Quirino

2018-04-11

Stress Echocardiography (SE) is an established diagnostic technique. For 40 years, the cornerstone of the technique has been the detection of regional wall motion abnormalities (RWMA), due to the underlying physiologically-relevant epicardial coronary artery stenosis. In the last decade, three new parameters (more objective than RWMA) have shown the potential to integrate and comple- ment RWMA: 1- B-lines, also known as ultrasound lung comets, as a marker of extra-vascular lung water, measured using lung ultrasound with the 4-site simplified scan symmetrically of the antero- lateral thorax on the third intercostal space, from mid-axillary to anterior axillary and mid- clavicular line; 2-left ventricular contractile reserve (LVCR), assessed as the peak stress/rest ratio of left ventricular force, also known as elastance (systolic arterial pressure by cuff sphygmomanome- ter/end-systolic volume from 2D echocardiography); 3- coronary flow velocity reserve (CFVR) on left anterior descending coronary artery, calculated as peak stress/rest ratio of diastolic peak flow velocity assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and CFVR) now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in a one-stop shop the core "ABCD" (Asynergy+B-lines+Contractile reserve+Doppler flowmetry) protocol. It allows a synoptic assess- ment of parameters mirroring the epicardial artery stenosis (RWMA), interstitial lung water (B- lines), myocardial function (LVCR) and small coronary vessels (CFVR). Each variable has a clear clinical correlate, different and complementary to all others: RWMA identify an ischemic vs non- ischemic heart; B-lines a wet vs dry lung; LVCR a strong vs weak heart; CFVR a warm vs cold heart. IQ-SE is highly feasible, with minimal increase in the imaging and analysis time, and obvi- ous diagnostic and prognostic impact also beyond coronary artery disease - especially in heart fail- ure. Large scale effectiveness studies with IQ-SE are now under way with the Stress Echo 2020 study, and will provide the necessary evidence base prior to large scale acceptance of the tech- nique.

Real-time optoacoustic monitoring of stroke

NASA Astrophysics Data System (ADS)

Kneipp, Moritz; Turner, Jake; Hambauer, Sebastian; Krieg, Sandro M.; Lehmberg, Jens; Lindauer, Ute; Razansky, Daniel

2014-03-01

Characterizing disease progression and identifying possible therapeutic interventions in stroke is greatly aided by the use of longitudinal function imaging studies. In this study, we investigate the applicability of real-time multispectral optoacoustic tomography (MSOT) as a tool for non-invasive monitoring of the progression of stroke in the whole brain. The middle cerebral artery occlusion (MCAO) method was used to induce stroke. Mice were imaged under isoflurane anesthesia preoperatively and at several time points during and after the 60-minute occlusion. The animals were sacrificed after 24 hours and their excised brains frozen at -80°C for sectioning. The cryosection were stained using H&E staining to identify the ischemic lesion. Major vessels are readily identifiable in the whole mouse head in the in vivo optoacoustic scans. During ischemia, a reduction in cerebral blood volume is detectable in the cortex. Post ischemia, spectral unmixing of the optoacoustic signals shows an asymmetry of the deoxygenated hemoglobin in the hemisphere affected by MCAO. This hypoxic area was mainly located around the boundary of the ischemic lesion and was therefore identified as the ischemic penumbra. Non-invasive functional MSOT imaging is able to visualize the hypoxic penumbra in brains affected by stroke. Stopping the spread of the infarct area and revitalizing the penumbra is central in stroke research, this new imaging technique may therefore prove to be a valuable tool in the monitoring and developing new treatments.

Atrial fibrillation and risk of stroke in dialysis patients

PubMed Central

Wetmore, James B.; Ellerbeck, Edward F.; Mahnken, Jonathan D.; Phadnis, Milind; Rigler, Sally K.; Mukhopadhyay, Purna; Spertus, John A.; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I.

2013-01-01

Purpose Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. Methods A cohort of dually-eligible (Medicare & Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Results Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (HR 1.26, 99% CI’s 1.06 – 1.49, P = 0.0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African-Americans (HR 1.46, 99% CI’s 1.08 – 1.96), Hispanics (HR 1.64, 99% CI’s 1.16 – 2.31), and others (HR 1.76, 99% CI’s 1.16 – 2.78) had higher rates than did Caucasians (P < 0.001 for all). Conclusions Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes due to hemorrhage is much higher than in the general population. PMID:23332588

Atrial fibrillation and risk of stroke in dialysis patients.

PubMed

Wetmore, James B; Ellerbeck, Edward F; Mahnken, Jonathan D; Phadnis, Milind; Rigler, Sally K; Mukhopadhyay, Purna; Spertus, John A; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I

2013-03-01

Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. A cohort of dually eligible (Medicare and Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (hazard ratio [HR], 1.26; 99% confidence interval [CI], 1.06-1.49; P = .0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African Americans (HR, 1.46; 99% CI, 1.08-1.96), Hispanics (HR, 1.64; 99% CI, 1.16-2.31), and others (HR, 1.76; 99% CI, 1.16-2.78) had higher rates than did Caucasians (all P < .001). Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes owing to hemorrhage is much higher than in the general population. Copyright © 2013 Elsevier Inc. All rights reserved.

High Time Resolution Measurements of VOCs from Vehicle Cold Starts: The Air Toxic Cold Start Pulse

NASA Astrophysics Data System (ADS)

Jobson, B. T.; Huangfu, Y.; Vanderschelden, G. S.

2017-12-01

Pollutants emitted during motor vehicle cold starts, especially in winter in some climates, is a significant source of winter time air pollution. While data exist for CO, NO, and total hydrocarbon emissions from federal testing procedures for vehicle emission certification, little is known about the emission rates of individual volatile organic compounds, in particular the air toxics benzene, formaldehyde, and acetaldehyde. Little is known about the VOC speciation and temperature dependence for cold starts. The US EPA vehicle emission model MOVES assumes that cold start emissions have the same speciation profile as running emissions. We examined this assumption by measuring cold start exhaust composition for 4 vehicles fueled with E10 gasoline over a temperature range of -4°C to 10°C in winter of 2015. The extra cold start emissions were determined by comparison with emissions during engine idling. In addition to CO and NOx measurements a proton transfer reaction mass spectrometer was used to measure formaldehyde, acetaldehyde, benzene, toluene, and C2-alkylbenzenes at high time resolution to compare with the cold start emission speciation profiles used in the EPA MOVES2014 model. The results show that after the vehicle was started, CO mixing ratios can reach a few percent of the exhaust and then drop to several ppmv within 2 minutes of idling, while NOx showed different temporal behaviors among the four vehicles. VOCs displayed elevated levels during cold start and the peak mixing ratios can be two orders higher than idling phase levels. Molar emission ratios relative to toluene were used to compare with the emission ratio used in MOVES2014 and we found the formaldehyde-to-toluene emission ratio was about 0.19, which is 5 times higher than the emission ratio used in MOVES2014 and the acetaldehyde-to-toluene emission ratios were 0.86-0.89, which is 8 times higher than the ones in MOVES2014. The C2-alkylbenzene-to-toluene ratio agreed well with moves. Our results suggest that for the air toxics acetaldehyde and formaldehyde, wintertime cold temperature vehicle start emissions are likely significantly underestimated in the MOVES 2014 model.

Mortality related to extreme temperature for 15 cities in northeast Asia.

PubMed

Chung, Yeonseung; Lim, Youn-Hee; Honda, Yasushi; Guo, Yue-Liang Leon; Hashizume, Masahiro; Bell, Michelle L; Chen, Bing-Yu; Kim, Ho

2015-03-01

Multisite time-series studies for temperature-related mortality have been conducted mainly in the United States and Europe, but are lacking in Asia. This multisite time-series study examined mortality related to extreme temperatures (both cold and hot) in Northeast Asia, focusing on 15 cities of 3 high-income countries. This study includes 3 cities in Taiwan for 1994-2007, 6 cities in Korea for 1992-2010, and 6 cities in Japan for 1972-2009. We used 2-stage Bayesian hierarchical Poisson semiparametric regression to model the nonlinear relationship between temperature and mortality, providing city-specific and country-wide estimates for cold and heat effects. Various exposure time frames, age groups, and causes of death were considered. Cold effects had longer time lags (5-11 days) than heat effects, which were immediate (1-3 days). Cold effects were larger for cities in Taiwan, whereas heat effects were larger for cities in Korea and Japan. Patterns of increasing effects with age were observed in both cold and heat effects. Both cold and heat effects were larger for cardiorespiratory mortality than for other causes of death. Several city characteristics related to weather or air pollution were associated with both cold and heat effects. Mortality increased with either cold or hot temperature in urban populations of high-income countries in Northeast Asia, with spatial variations of effects among cities and countries. Findings suggest that climate factors are major contributors to the spatial heterogeneity of effects in this region, although further research is merited to identify other factors as determinants of variability.

Evaluation of Collaterals and Clot Burden Using Time-Resolved C-Arm Conebeam CT Angiography in the Angiography Suite: A Feasibility Study.

PubMed

Yang, P; Niu, K; Wu, Y; Struffert, T; Doerfler, A; Holter, P; Aagaard-Kienitz, B; Strother, C; Chen, G-H

2017-04-01

The assessment of collaterals and clot burden in patients with acute ischemic stroke provides important information about treatment options and clinical outcome. Time-resolved C-arm conebeam CT angiography has the potential to provide accurate and reliable evaluations of collaterals and clot burden in the angiographic suite. Experience with this technique is extremely limited, and feasibility studies are needed to validate this technique. Our purpose was to present such a feasibility study. Ten C-arm conebeam CT perfusion datasets from 10 subjects with acute ischemic stroke acquired before endovascular treatment were retrospectively processed to generate time-resolved conebeam CTA. From time-resolved conebeam CTA, 2 experienced readers evaluated the clot burden and collateral flow in consensus by using previously reported scoring systems and assessed the clinical value of this novel imaging technique independently. Interobserver agreement was analyzed by using the intraclass correlation analysis method. Clot burden and collateral flow can be assessed by using the commonly accepted scoring systems for all eligible cases. Additional clinical information (eg, the quantitative dynamic information of collateral flow) can be obtained from this new imaging technique. Two readers agreed that time-revolved C-arm conebeam CTA is the preferred method for evaluating the clot burden and collateral flow compared with other conventional imaging methods. Comprehensive evaluations of clot burden and collateral flow are feasible by using time-resolved C-arm conebeam CTA data acquired in the angiography suite. This technique further enriches the imaging tools in the angiography suite to enable a "one-stop- shop" imaging workflow for patients with acute ischemic stroke. © 2017 by American Journal of Neuroradiology.

Effects of So-cheong-ryong-tang and Yeon-gyo-pae-dok-san on the common cold: randomized, double blind, placebo controlled trial.

PubMed

Byun, Jun-Seop; Yang, Su-Young; Jeong, In-Cheol; Hong, Kwon-Eui; Kang, Weechang; Yeo, Yoon; Park, Yang-Chun

2011-01-27

So-cheong-ryong-tang (SCRT) and Yeon-gyo-pae-dok-san (YPS) extracts are widely used in treatment of the common cold. The purpose of this study is to evaluate the efficacy of SCRT and YPS on the common cold. Four hundred eighty participants with symptoms of the common cold within 48 h were recruited for this randomized, double-blind, placebo-controlled trial. SCRT extract and YPS extract were put in gelatin capsules and orally administered 3 times a day. The pattern of participants was determined according to the Questionnaire for Common Cold Pattern Identification (QCCPI), and the severity of illness was assessed by Wisconsin Upper Respiratory Symptom Survey-21 Korean version (WURSS-21-K) every 7 days. The test and control groups were not significantly different in gender, age, smoking history, and baseline score of WURSS-21-K at the time of enrollment. SCRT treatment significantly decreased the total WURSS-21-K score on the 6th and 7th day (p<0.05) of the enrollment compared with the placebo group. YPS treatment decreased the total WURSS-21-K score on the 5th and 6th day (p<0.05 vs. the placebo group) of the enrollment. In the patients with Wind-cold pattern cold, SCRT significantly decreased the total WURSS-21-K score from 4th to 8th day (p<0.05), and YPS significantly decreased the total WURSS-21-K score from 4th to 6th day (p<0.05). For the Wind-heat pattern cold, neither SCRT nor YPS group showed significant difference from the placebo group. SCRT and YPS did not significantly decrease the time to complete resolution of the cold symptoms. SCRT and YPS have beneficial, albeit limited, effects on common cold patients, especially those with the Wind-cold pattern cold. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The relation between cerebral blood flow velocities as measured by TCD and the incidence of delayed ischemic deficits. A prospective study after subarachnoid hemorrhage.

PubMed

Jarus-Dziedzic, Katarzyna; Juniewicz, Henryk; Wroñski, Jerzy; Zub, Wojciech Leslaw; Kasper, Ekkehard; Gowacki, Mariusz; Mierzwa, Janusz

2002-09-01

Patients (n = 127) with aneurysmal subarachnoid hemorrhage (SAH) were examined by transcranial Doppler ultrasonography (TCD) in a prospective study to follow the time course of the posthemorrhagic blood flow velocity in both the middle cerebral artery (MCA) and in the anterior cerebral artery (ACA). Results were analysed to reveal their relationship and predictive use with respect to the occurrence of delayed ischemic deficits. Mean flow velocities (MFV) higher than 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA were interpreted as indicative for significant vasospasm. In 20 of our 127 patients (16%) a delayed ischemic deficit (DID) was subsequently diagnosed clinically (DID+ group). Patients in the DID+ group can be characterized as those individuals who presented early during the observation period post-SAH with highest values of MFV, a faster increase and longer persistence of pathologically elevated MFV-values (exceeding 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA). They also show a greater difference in MFV-values if one compares the operated to the nonoperated side. Differences in MFV-values obtained in MCA or ACA were statistically significant (p < 0.05) for DID+ and DID- patients. The daily maximal increase of MFV was found between days 9 and 11 after SAH. In the DID+ group, the maximal MFV was 181 +/- 26 cm sec(-1) in MCA and 119 +/- 14 cm sec(-1) in ACA. In contrast to this, patients in the DID- group were found to present with MFV of 138 +/- 11 cm sec(-1) in MCA and 100 +/- 7 cm sec(-1) in ACA respectively. Delayed ischemic deficits appeared three times more often in DID+ patients than in patients with MFV < 120 cm sec(-1), if they showed a MFV > 120 cm sec(-1) in MCA. If pathological values were obtained in ACA, this ratio increases to about four times, if DID + patients presented with MFV > 90 cm sec(-1) versus patients with MFV < 90 cm sec(-1). Daily monitoring of vasospasm using TCD examination is thus helpful to identify patients at high risk for delayed ischemic deficits. This should allow us to implement further preventive treatment regimens.

Modeling and Experiments on Fast Cooldown of a 120 Hz Pulse Tube Cryocooler

NASA Astrophysics Data System (ADS)

Vanapalli, Srinivas; Lewis, Michael; Grossman, Gershon; Gan, Zhihua; Radebaugh, Ray; Brake, H. J. M. ter

2008-03-01

High frequency operation of a pulse tube cryocooler leads to reduced regenerator volume, which results in a reduced heat capacity and a faster cooldown time. A pulse tube cryocooler operating at a frequency of 120 Hz and an average pressure of 3.5 MPa achieved a no-load temperature of 50 K. The cooling power at 80 K was about 3.35 W with a cooldown time from 285 K to 80 K of about 5.5 minutes, even though the additional thermal mass at the cold end due to flanges, screws, heater, and thermometer was 4.2 times that of the regenerator. This fast cooldown is about two to four times faster than that of typical pulse tube cryocoolers and is very attractive to many applications. In this study we measure the cooldown time to 80 K for different cold-end masses and extrapolate to zero cold-end mass. We also present an analytical model for the cooldown time for different cold-end masses and compare the results with the experiments. The model and the extrapolated experimental results indicate that with zero cold-end mass the cooldown time to 80 K with this 120 Hz pulse tube cryocooler would be about 32 s.

Cardiovascular Toxicity of Multi-Tyrosine Kinase Inhibitors in Advanced Solid Tumors: A Population-Based Observational Study

PubMed Central

Srikanthan, Amirrtha; Ethier, Josee-Lyne; Ocana, Alberto; Seruga, Bostjan; Krzyzanowska, Monika K.; Amir, Eitan

2015-01-01

Background Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. Methods A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. Results 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. Conclusions TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer. PMID:25815472

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies

PubMed Central

Wever, Kimberley E.; Hooijmans, Carlijn R.; Riksen, Niels P.; Sterenborg, Thomas B.; Sena, Emily S.; Ritskes-Hoitinga, Merel; Warlé, Michiel C.

2015-01-01

Background Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients. Objective To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation. Methods and results Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2–3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively. Conclusions Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence. PMID:26580958

Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation.

PubMed

Flint, Alexander C; Conell, Carol; Ren, Xiushui; Kamel, Hooman; Chan, Sheila L; Rao, Vivek A; Johnston, S Claiborne

2017-07-01

Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib). We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system. Among 6116 patients with ischemic stroke discharged on a statin over a 5-year period, 1446 (23.6%) had a diagnosis of AFib at discharge. The mean statin adherence rate (percentage of days covered) was 85, and higher levels of percentage of days covered correlated with greater degrees of low-density lipoprotein suppression. In multivariable survival models of recurrent ischemic stroke over 3 years, after controlling for age, sex, race/ethnicity, medical comorbidities, and hospital center, higher statin adherence predicted reduced stroke risk both in patients without AFib (hazard ratio, 0.78; 95% confidence interval, 0.63-0.97) and in patients with AFib (hazard ratio, 0.59; 95% confidence interval, 0.43-0.81). This association was robust to adjustment for the time in the therapeutic range for international normalized ratio among AFib subjects taking warfarin (hazard ratio, 0.61; 95% confidence interval, 0.41-0.89). The relationship between statin adherence and reduced recurrent stroke risk is as strong among patients with AFib as it is among patients without AFib, suggesting that AFib status should not be a reason to exclude patients from secondary stroke prevention with a statin. © 2017 American Heart Association, Inc.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort

PubMed Central

Son, Mi Kyoung; Lim, Nam-Kyoo; Kim, Hyung Woo

2017-01-01

Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007–2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6%) patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients) associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32–0.53). Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days) continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed. PMID:28636620

Attitudes and barriers to the use of donation after cardiac death livers: Comparison of a United States transplant center survey to the united network for organ sharing data.

PubMed

Sher, Linda; Quintini, Cristiano; Fayek, Sameh Adel; Abt, Peter; Lo, Mary; Yuk, Pui; Ji, Lingyun; Groshen, Susan; Case, Jamie; Marsh, Christopher Lee

2017-11-01

Transplantation of liver grafts from donation after cardiac death (DCD) is limited. To identify barriers of DCD liver utilization, all active US liver transplant centers (n = 138) were surveyed, and the responses were compared with the United Network for Organ Sharing (UNOS) data. In total, 74 (54%) centers responded, and diversity in attitudes was observed, with many not using organ and/or recipient prognostic variables defined in prior studies and UNOS data analysis. Most centers (74%) believed lack of a system allowing a timely retransplant is a barrier to utilization. UNOS data demonstrated worse 1- and 5-year patient survival (PS) and graft survival (GS) in DCD (PS, 86% and 64%; GS, 82% and 59%, respectively) versus donation after brain death (DBD) recipients (PS, 90% and 71%; GS, 88% and 69%, respectively). Donor alanine aminotransferase (ALT), recipient Model for End-Stage Liver Disease (MELD), and cold ischemia time (CIT) significantly impacted DCD outcomes to a greater extent than DBD outcomes. At 3 years, relisting and retransplant rates were 7.9% and 4.6% higher in DCD recipients. To optimize outcome, our data support the use of DCD liver grafts with CIT <6-8 hours in patients with MELD ≤ 20. In conclusion, standardization of donor and recipient criteria, defining the impact of ischemic cholangiopathy, addressing donor hospital policies, and developing a strategy for timely retransplant may help to expand the use of these organs. Liver Transplantation 23 1372-1383 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Blood flow dynamics in heart failure

NASA Technical Reports Server (NTRS)

Shoemaker, J. K.; Naylor, H. L.; Hogeman, C. S.; Sinoway, L. I.

1999-01-01

BACKGROUND: Exercise intolerance in heart failure (HF) may be due to inadequate vasodilation, augmented vasoconstriction, and/or altered muscle metabolic responses that lead to fatigue. METHODS AND RESULTS: Vascular and metabolic responses to rhythmic forearm exercise were tested in 9 HF patients and 9 control subjects (CTL) during 2 protocols designed to examine the effect of HF on the time course of oxygen delivery versus uptake (protocol 1) and on vasoconstriction during exercise with 50 mm Hg pressure about the forearm to evoke a metaboreflex (protocol 2). In protocol 1, venous lactate and H+ were greater at 4 minutes of exercise in HF versus CTL (P<0.05) despite similar blood flow and oxygen uptake responses. In protocol 2, mean arterial pressure increased similarly in each group during ischemic exercise. In CTL, forearm blood flow and vascular conductance were similar at the end of ischemic and ambient exercise. In HF, forearm blood flow and vascular conductance were reduced during ischemic exercise compared with the ambient trial. CONCLUSIONS: Intrinsic differences in skeletal muscle metabolism, not vasodilatory dynamics, must account for the augmented glycolytic metabolic responses to moderate-intensity exercise in class II and III HF. The inability to increase forearm vascular conductance during ischemic handgrip exercise, despite a normal pressor response, suggests that enhanced vasoconstriction of strenuously exercising skeletal muscle contributes to exertional fatigue in HF.

A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.

PubMed

Tam, Jacqueline Chor-Wing; Ko, Chun-Hay; Lau, Kit-Man; To, Ming-Ho; Kwok, Hin-Fai; Chan, Yuet-Wa; Siu, Wing-Sum; Etienne-Selloum, Nelly; Lau, Ching-Po; Chan, Wai-Yee; Leung, Ping-Chung; Fung, Kwok-Pui; Schini-Kerth, Valérie B; Lau, Clara Bik-San

2014-01-01

Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow cytometric analysis revealed that NF3 could boost circulating EPC levels for local wound vessel incorporation. Immunohistochemical analysis showed that NF3 could significantly augment blood vessel density, VEGF and eNOS expression, and attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3 significantly stimulated MMP activity involved in angiogenesis. Our study shows, for the first time, the beneficial effects of NF3 in wound healing and post-ischemic neovascularization in diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

PubMed

Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

2011-12-31

An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.

PubMed

Jeong, Hoon Jae; Kim, Dae Won; Kim, Mi Jin; Woo, Su Jung; Kim, Hye Ri; Kim, So Mi; Jo, Hyo Sang; Hwang, Hyun Sook; Kim, Duk Soo; Cho, Sung Woo; Won, Moo Ho; Han, Kyu Hyung; Park, Jin Seu; Eum, Won Sik; Choi, Soo Young

2012-10-31

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a doseand time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation

PubMed Central

Vinding, Mikkel C.; Allen, Micah; Jensen, Troels Staehelin; Finnerup, Nanna Brix

2017-01-01

Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1–4 Hz) and gamma (55–90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas. NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage. PMID:28250150

Mitral valve repair for ischemic moderate mitral regurgitation in patients undergoing coronary artery bypass grafting

PubMed Central

Toktas, Faruk; Yavuz, Senol; Ozsin, Kadir K.; Sanri, Umut S.

2016-01-01

Objectives: To investigate whether mitral valve repair (MVR) at the time of coronary artery bypass grafting (CABG) in patients with ischemic moderate mitral regurgitation (MR) and coronary artery disease could improve short- and mid-term postoperative outcomes. Methods: Between March 2013 and December 2015, 90 patients with moderate ischemic MR underwent first-time CABG in Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey. Out of 90 patients, 44 (48.9%) underwent combined CABG+MVR. The remaining 46 (51.1%) underwent CABG alone. Ventricular functions and effort capacities of patients in both groups were evaluated echocardiographically and clinically in the preoperative period, and in the first postoperative year. Results: Postoperative regurgitant volume changes according to preoperative values were -24.76±19 ml/beat in the combined CABG+MVR group, and -8.70±7.2 ml/beat in the CABG alone group (p=0.001). The change of vena contracta width was -3.40±0.2 mm in the combined CABG+MVR group whereas in the CABG alone -1.45±0.7 mm (p=0.019). The changes of left ventricular end-systolic volume index were -30.77±25.9 ml/m2 in the combined CABG+MVR group and -15.6±9.4 ml/m2 in the CABG alone group (p=0.096). Ejection fraction changes in the combined CABG+MVR group was +1.51±5.3% and in the CABG alone group was +1.15±4.3%. No statistically significant difference was found between both groups (p=0.604). Preoperative New York Heart Association class values in the combined CABG+MVR group was 2.18±0.45, and in the CABG alone group was 2.13±0.54. Conclusions: Moderate MR in patients undergoing CABG affects the outcome adversely and it does not reliably improve after CABG alone. Therefore, patients with ischemic moderate MR should undergo simultaneous MVR at the time of CABG. PMID:27464861

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

DOE PAGES

Rodriguez-Fernandez, P.; White, A. E.; Howard, N. T.; ...

2018-02-16

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. Here, this Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and timemore » scales of cold-pulse experiments in tokamak plasmas.« less

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Fernandez, P.; White, A. E.; Howard, N. T.

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. Here, this Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and timemore » scales of cold-pulse experiments in tokamak plasmas.« less

Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.

PubMed

Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung; Rothwell, Peter M

2017-06-01

Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P <0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P <0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78-1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P =0.011) but not intracerebral hemorrhage ( P =0.10) or all-cause mortality ( P =0.16). CS-PVSs were not associated with recurrent stroke ( P =0.57) or mortality ( P =0.072). Prognostic associations were similar in both cohorts. Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. © 2017 The Authors.

Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke

PubMed Central

Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E.; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung

2017-01-01

Background and Purpose— Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Methods— Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Results— Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11–20 PVSs: HR, 1.15; 95% confidence interval, 0.78–1.68; >20 PVSs: HR, 1.82; 1.18–2.80; P=0.011) but not intracerebral hemorrhage (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were similar in both cohorts. Conclusions— Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. PMID:28495831

Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease

PubMed Central

van Golen, Rowan F.; Stevens, Katarzyna M.; Colarusso, Pina; Jaeschke, Hartmut; Heger, Michal

2016-01-01

Background Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers. Aims To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils. Methods Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software. Results Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils. Conclusions Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation. Relevance for patients I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I/R injury and improving clinical outcomes. PMID:26925465

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer.

PubMed

Addison, Daniel; Seidelmann, Sara B; Janjua, Sumbal A; Emami, Hamed; Staziaki, Pedro V; Hallett, Travis R; Szilveszter, Bálint; Lu, Michael T; Cambria, Richard P; Hoffmann, Udo; Chan, Annie W; Wirth, Lori J; Neilan, Tomas G

2017-08-30

Radiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown. Using an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV-positive and -negative patients. Over a median follow-up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV-positive patients compared with the HPV-negative patients (2.6% versus 0.9%, P =0.002). In a multivariable model, HPV-positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5-13.2; P =0.008). In this study, HPV-positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Using a Harmonic Scalpel "Drilling and Clamping" Method to Implement Zero Ischemic Robotic-assisted Partial Nephrectomy: An Observation Case Report Study.

PubMed

Hou, Chen-Pang; Lin, Yu-Hsiang; Hsu, Yu-Chao; Chen, Chien-Lun; Chang, Phei-Lang; Tsui, Ke-Hung

2016-01-01

Robot-assisted partial nephrectomy (RAPN) has gradually become a popular minimally invasive nephron-sparing surgical option for small renal tumors. Ischemic injury should be minimized because it impacts renal function outcomes following partial nephrectomy. Herein, the authors detail the technique and present initial perioperative outcomes of our novel harmonic scalpel "drilling and clamping" method to implement zero-ischemic RAPN. The authors prospectively collected baseline and perioperative data of patients who underwent zero ischemic RAPN performed by our harmonic scalpel "drilling and clamping" method. From April 2012 to December 2014, a total of 19 consecutive zero ischemic RAPN procedures were performed by a single surgeon. For 18 of the 19 patients, RAPN using our harmonic scalpel "Drilling and Clamping" method was successfully completed without the need for hilar clamping. The median tumor size was 3.4 cm (range: 1.8-6.2); operative time was 3.2 hours (range: 1.9-4.5); blood loss was 100 mL (range: 30-950); and postoperative hospital stay was 4 days (3-26). One patient required intraoperative blood transfusion. Two patients had intra or postoperative complications: 1 was converted to traditional laparotomy because of massive bleeding, whereas another had postoperative stress ulcer. Pathology confirmed renal cell carcinoma in 13 patients (63.2%), angiomyolipoma in 6 patients: (31.5%), and oncocytoma in 1 patient (5.3%). Mean pre- and postoperative serum creatinine (0.82 mg/dL and 0.85 mg/dL, respectively), estimated glomerular filtration rate (84.12 and 82.18, respectively), and hemoglobin (13.27 g/dL and 12.71 g/dL, respectively) were comparable. The authors present a novel zero-ischemic technique for RAPN. They believe that this technique is feasible and reproducible.

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PubMed

Johnston, S Claiborne; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence

2016-07-07

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Comparison of Warfarin use in terms of efficacy and safety in two different polyclinics

PubMed Central

Kılıç, Salih; Kemal, Hatice Soner; Yüce, Elif İlkay; Şimşek, Evrim; Yağmur, Burcu; Akgül, Nuray Memişoğlu; Çınar, Cahide Soydaş; Zoghi, Mehdi; Gürgün, Cemil

2017-01-01

Objective: This study compared the efficacy and safety of warfarin in specialized international normalized ratio (INR) outpatient clinic (INR-C) and in general cardiology outpatient clinic (General-C). Methods: Herein, 381 consecutive patients with a regular follow-up at INR-C (n=233) or General-C (n=148) for at least 1 year were retrospectively included. While INR-C patients were followed by a single experienced trained nurse, General-C patients were followed by a different cardiologist who worked in a rotational principle every month. During controls, demographic characteristics, INR levels, bleeding events, ischemic stroke, and transient ischemic attacks in the last 1 year were recorded. Primary endpoint was defined as the evaluation of the combined major bleeding and ischemic event, and secondary endpoint was defined as the evaluation of them separately. Results: The mean age of the patients was 62±12.86 and 43.8% were male. Mean time in therapeutic range (TTR) level was statistically higher in INR-C than that in General-C (68.8%±15.88 and 51.6%±23.04, respectively; p<0.001). Primary outcomes were significantly higher in General-C than that in INR-C [13.5% (20) and 6.4% (15); respectively, p=0.020]. Overall, major bleeding was observed in 25 patients (6.5%) and (2.6%) ischemic event was observed in 10 patients. In General-C patients, both major bleeding (8.8% vs. 5.2%; p=0.163) and the ischemic event (4.7% vs. 1.3%; p=0.051) were more, and no statistically significant differences were detected between the two clinics. Conclusion: The findings of our study demonstrate that patients followed in INR-C had higher TTR levels and lower bleeding and ischemic events rates that those followed in General-C. PMID:29145216

Risk of acute stroke after hospitalization for sepsis: A case-crossover study

PubMed Central

Boehme, Amelia K.; Ranawat, Purnima; Luna, Jorge; Kamel, Hooman; Elkind, Mitchell S. V.

2017-01-01

Background and Purpose Infections have been found to increase the risk of stroke over the short-term. We hypothesized that stroke risk would be highest shortly after a sepsis hospitalization, but that the risk would decrease, yet remain up to 1-year after sepsis. Methods This case-crossover analysis utilized data obtained from the California State Inpatient Database of the Healthcare Cost and Utilization Project (HCUP). All stroke admissions were included. Exposure was defined as hospitalization for sepsis or septicemia 180, 90, 30 or 15 days before stroke (risk period) or similar time intervals exactly 1 or 2 years before stroke (control period). Conditional logistic regression was used to calculate the odds ratio and 95% confidence interval (OR, 95% CI) for the association between sepsis/septicemia and ischemic or hemorrhagic stroke. Results Ischemic (n=37,377) and hemorrhagic (n=12,817) strokes that occurred in 2009 were extracted where 3188 (8.5%) ischemic and 1101 (8.6%) hemorrhagic stroke patients had sepsis. Sepsis within 15 days prior to the stroke placed patients at the highest risk of ischemic (OR 28.36, 95% CI 20.02 –40.10) and hemorrhagic stroke (OR 12.10, 95% CI 7.54–19.42); however while the risk decreased, it remained elevated 181- 365 days after sepsis for ischemic (OR 2.59, 95%CI 2.20–3.06) and hemorrhagic (O 3.92, 95%CI 3.29–4.69) strokes. There was an interaction with age (p=0.0006); risk of developing an ischemic stroke within 180 days of hospitalization for sepsis increased 18% with each 10-year decrease in age. Conclusion Risk of stroke is high after sepsis, and this risk persists for up to a year. Younger sepsis patients have a particularly increased risk of stroke after sepsis. PMID:28196938

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

PubMed Central

2012-01-01

Background Certain immune-mediated diseases (IMDs) have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 different IMDs and first hospitalization for ischemic or hemorrhagic stroke. Methods All individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke), between January 1, 1987 and December 31, 2008 (n = 216,291), were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs) for ischemic and hemorrhagic stroke were calculated. Results Totally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95% CI 1.90–2.14) and 2.65 (95% CI 2.27–3.08), respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95% CI 1.46–1.55) and 1.83 (95% CI 1.69–1.98), respectively, after 1–5 years, and 1.29 (95% CI 1.23–1.35) and 1.47 (95% CI 1.31–1.65), respectively, after 10+ years. The risk of hemorrhagic stroke was ≥2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11), immune thrombocytopenic purpura (SIR = 8.60), polymyalgia rheumatica (SIR = 2.06), psoriasis (SIR = 2.88), rheumatoid arthritis (SIR = 3.27), systemic lupus erythematosus (SIR = 8.65), and Wegener´s granulomatosis (SIR = 5.83). The risk of ischemic stroke was ≥2 during the first year after hospitalization for twelve IMDs: Addison’s disease (SIR = 2.71), Crohn´s disease (SIR = 2.15), Grave´s disease (SIR = 2.15), Hashimoto´s thyroiditis (SIR = 2.99), immune thrombocytopenic purpura (SIR = 2.35), multiple sclerosis (SIR = 3.05), polymyositis/dermatomyositis (SIR = 3.46), rheumatic fever (SIR = 3.91), rheumatoid arthritis (SIR = 2.08), Sjögren’s syndrome (SIR = 2.57), systemic lupus erythematosus (SIR = 2.21), and ulcerative colitis (SIR = 2.15). Conclusions Hospitalization for many IMDs is associated with increased risk of ischemic or hemorrhagic stroke. The findings suggest that several IMDs are linked to cerebrovascular disease. PMID:22708578

Development of an ion-pair HPLC method for investigation of energy charge changes in cerebral ischemia of mice and hypoxia of Neuro-2a cell line.

PubMed

Chen, Yunyun; Xing, Dongming; Wang, Wei; Ding, Yi; Du, Lijun

2007-06-01

The determination of adenine nucleotides and energy charge (EC) has great importance in the characterization of cerebral ischemic injury and post-ischemic recovery. An IP-HPLC method was developed for the quantification of AMP, ADP, ATP and EC in cerebral ischemia and hypoxia of the Neuro-2a cell line. The chromatographic conditions were: a Zorbax SB-C18 reversed-phase column; mobile phase 100 mM KH(2)PO(4), 1 mM tetrabutylammonium hydroxide, and 2.5% acetonitrile, brought to pH 7.0 with potassium hydroxide (4 M), filtered through a 0.45 microm Millipore filter and degassed prior to use. The flow-rate was 1.0 mL/min. The injection volume was 20 microL. Detection was performed at a wavelength of 254 nm under a constant temperature (27 +/- 1 degrees C). The method was validated by means of linearity, using calibration curves constructed with five concentration levels of each compound. The limit of detection was also determined. The system precision was calculated as the coefficient of variation for five injections for each compound tested. Cerebral tissue was homogenized (4 degrees C) in 1 mL of an ice-cold 6% trichloroacetic acid that contained ATPase inhibitor and obtained good recovery (>90%). The results show that the described method for the determination of adenine nucleotides by HPLC has good linearity, limit of detection, precision and specificity, and is simple and rapid to perform. Copyright 2007 John Wiley & Sons, Ltd.

A Randomized Controlled Trial of Acupuncture in Stable Ischemic Heart Disease Patients

PubMed Central

Mehta, Puja K.; Polk, Donna M.; Zhang, Xiao; Li, Ning; Painovich, Jeannette; Kothawade, Kamlesh; Kirschner, Joan; Qiao, Yi; Ma, Xiuling; Chen, Yii-Der Ida; Brantman, Anna; Shufelt, Chrisandra; Minissian, Margo; Bairey Merz, C. Noel

2014-01-01

Background Heart rate variability (HRV) is reduced in stable ischemic heart disease (SIHD) patients and is associated with sudden cardiac death (SCD). We evaluated the impact of traditional acupuncture (TA) on cardiac autonomic function measured by HRV in SIHD patients. Methods We conducted a randomized controlled study of TA, sham acupuncture (SA), and waiting control (WC) in 151 SIHD subjects. TA group received needle insertion at acupuncture sites, SA group received a sham at non-acupuncture sites, while WC received nothing. TA and SA received 3 treatments/week for 12 wks. 24-hour, mental arithmetic stress, and cold pressor (COP) HRV was collected at entry and exit, along with BP, lipids, insulin resistance, hs-CRP, salivary cortisol, peripheral endothelial function by tonometry(PAT), and psychosocial variables. Results Mean age was 63±10; 50% had prior myocardial infarction. Comparison of WC and SA groups demonstrated differences consistent with the unblinded WC status; therefore by design, the control groups were not merged. Exit mental stress HRV was higher in TA vs. SA for markers of parasympathetic tone (p≤0.025), including a 17% higher vagal activity (p=0.008). There were no differences in exit 24-hour or COP HRV, BP, lipids, insulin resistance, hs-CRP, salivary cortisol, PAT, or psychosocial variables. Conclusions TA results in intermediate effects on autonomic function in SIHD patients. TA effect on HRV may be clinically relevant and should be explored further. These data document feasibility and provide sample size estimation for a clinical trial of TA in SIHD patients for prevention of SCD. PMID:25103909

[Metabolic intolerance to exercise].

PubMed

Arenas, J; Martín, M A

2003-01-01

Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC.

Loss-of-function mutations in APOC3 and risk of ischemic vascular disease.

PubMed

Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2014-07-03

High plasma levels of nonfasting triglycerides are associated with an increased risk of ischemic cardiovascular disease. Whether lifelong low levels of nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein C3 (APOC3) are associated with a reduced risk of ischemic cardiovascular disease in the general population is unknown. Using data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease. Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10,797 participants, and ischemic heart disease developed in 7557 of these 10,797 participants. Participants with nonfasting triglyceride levels of less than 1.00 mmol per liter (90 mg per deciliter) had a significantly lower incidence of cardiovascular disease than those with levels of 4.00 mmol per liter (350 mg per deciliter) or more (hazard ratio for ischemic vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss-of-function mutations in APOC3, as compared with no APOC3 mutations, was associated with a mean reduction in nonfasting triglyceride levels of 44% (P<0.001). The cumulative incidences of ischemic vascular disease and ischemic heart disease were reduced in heterozygotes as compared with noncarriers of APOC3 mutations (P=0.009 and P=0.05, respectively), with corresponding risk reductions of 41% (hazard ratio, 0.59; 95% CI, 0.41 to 0.86; P=0.007) and 36% (hazard ratio, 0.64; 95% CI, 0.41 to 0.99; P=0.04). Loss-of-function mutations in APOC3 were associated with low levels of triglycerides and a reduced risk of ischemic cardiovascular disease. (Funded by the European Union and others.).

Process optimization of ultrasound-assisted alcoholic-alkaline treatment for granular cold water swelling starches.

PubMed

Zhu, Bo; Liu, Jianli; Gao, Weidong

2017-09-01

This paper reports on the process optimization of ultrasonic assisted alcoholic-alkaline treatment to prepare granular cold water swelling (GCWS) starches. In this work, three statistical approaches such as Plackett-Burman, steepest ascent path analysis and Box-Behnken design were successfully combined to investigate the effects of major treatment process variables including starch concentration, ethanol volume fraction, sodium hydroxide dosage, ultrasonic power and treatment time, and drying operation, that is, vacuum degree and drying time on cold-water solubility. Results revealed that ethanol volume fraction, sodium hydroxide dosage, applied power and ultrasonic treatment time were significant factors that affected the cold-water solubility of GCWS starches. The maximum cold-water solubility was obtained when treated at 400W of applied power for 27.38min. Optimum volume fraction of ethanol and sodium hydroxide dosage were 66.85% and 53.76mL, respectively. The theoretical values (93.87%) and the observed values (93.87%) were in reasonably good agreement and the deviation was less than 1%. Verification and repeated trial results indicated that the ultrasound-assisted alcoholic-alkaline treatment could be successfully used for the preparation of granular cold water swelling starches at room temperatures and had excellent improvement on the cold-water solubility of GCWS starches. Copyright © 2016. Published by Elsevier B.V.

AGN jet-driven stochastic cold accretion in cluster cores

NASA Astrophysics Data System (ADS)

Prasad, Deovrat; Sharma, Prateek; Babul, Arif

2017-10-01

Several arguments suggest that stochastic condensation of cold gas and its accretion on to the central supermassive black hole (SMBH) is essential for active galactic nuclei (AGNs) feedback to work in the most massive galaxies that lie at the centres of galaxy clusters. Our 3-D hydrodynamic AGN jet-ICM (intracluster medium) simulations, looking at the detailed angular momentum distribution of cold gas and its time variability for the first time, show that the angular momentum of the cold gas crossing ≲1 kpc is essentially isotropic. With almost equal mass in clockwise and counterclockwise orientations, we expect a cancellation of the angular momentum on roughly the dynamical time. This means that a compact accretion flow with a short viscous time ought to form, through which enough accretion power can be channeled into jet mechanical energy sufficiently quickly to prevent a cooling flow. The inherent stochasticity, expected in feedback cycles driven by cold gas condensation, gives rise to a large variation in the cold gas mass at the centres of galaxy clusters, for similar cluster and SMBH masses, in agreement with the observations. Such correlations are expected to be much tighter for the smoother hot/Bondi accretion. The weak correlation between cavity power and Bondi power obtained from our simulations also matches observations.

Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

PubMed

Liao, Z; Feng, Z; Long, C

2014-07-01

Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

Inspection of Space Station Cold Plate Using Visual and Automated Holographic Techniques

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Melis, Matthew E.; Weiland, Kenneth E.

1999-01-01

Real-time holography has been used to confirm the presence of non-uniformity in the construction of an International Space Station cold plate. Ultrasonic C-scans have previously shown suspected areas of cooling fin disbonds. But both neural-net processed and visual holography did not evidence any progressive permanent changes resulting from 3000 pressurization and relaxation cycles of a Dash 8 cold plate. Neural-net and visual inspections were performed of characteristic patterns generated from electronic time-average holograms of the vibrating cold plate. Normal modes of vibration were excited at very low amplitudes for this purpose, The neural nets were trained to flag very small changes in the mode shapes as encoded in the characteristic patterns. Both the whole cold plate and a zoomed region were inspected. The inspections were conducted before, after, and during pressurization and relaxation cycles of the cold plate. A water-filled cold plate was pressurized to 120 psig (827 kPa) and relaxed for each cycle. Each cycle required 5 seconds. Both the artificial neural networks and the inspectors were unable to detect changes in the mode shapes of the relaxed cold plate. The cold plate was also inspected visually using real-time holography and double-exposure holography. Regions of non-uniformity correlating with the C-scans were apparent, but the interference patterns did not change after 3000 pressurization and relaxation cycles. These tests constituted the first practical application of a neural-net inspection technique developed originally with support from the Director's Discretionary Fund at the Glenn Research Center at Lewis Field.

Cold-Weather Sports

MedlinePlus

... Videos for Educators Search English Español Cold-Weather Sports KidsHealth / For Teens / Cold-Weather Sports What's in this article? What to Do? Classes ... weather. What better time to be outdoors? Winter sports can help you burn calories, increase your cardiovascular ...

One-step reconstruction of the right inferior hepatic veins using auto-venous grafts in living-donor liver transplantation.

PubMed

Ikegami, Toru; Shirabe, Ken; Yoshiya, Shohei; Soejima, Yuji; Yoshizumi, Tomoharu; Uchiyama, Hideaki; Toshima, Takeo; Motomura, Takashi; Maehara, Yoshihiko

2013-07-01

Reconstruction of the right inferior hepatic vein (RIHV) presents a major technical challenge in living donor liver transplantation (LDLT) using right lobe grafts. We studied 47 right lobe LDLT grafts with RIHV revascularization, comparing one-step reconstruction, performed post-May 2007 (n = 16), with direct anastomosis, performed pre-May 2007 (n = 31). In the one-step reconstruction technique, the internal jugular vein (n = 6), explanted portal vein (n = 5), inferior vena cava (n = 3), and shunt vessels (n = 2) were used as venous patch grafts for unifying the right hepatic vein, RIHVs, and middle hepatic vein tributaries. By 6 months after LDLT, there was no case of occlusion of the reconstructed RIHVs in the one-step reconstruction group, but a cumulative occlusion rate of 18.2 % in the direct anastomosis group. One-step reconstruction required a longer cold ischemic time (182 ± 40 vs. 115 ± 63, p < 0.001) and these patients had higher alanine transaminase values (142 ± 79 vs. 96 ± 46 IU/L, p = 0.024) on postoperative day POD 7. However, the 6-month short-term graft survival rates were 100 % with one-step reconstruction and 83.9 % with direct anastomosis, respectively. One-step reconstruction of the RIHVs using auto-venous grafts is an easy and feasible technique promoting successful right lobe LDLT.

The Organ Allocation Controversy: How Did We Arrive Here?

PubMed Central

Van Meter, Clifford H.

1999-01-01

The Department of Health and Human Services (HHS) recently issued a final regulation governing the Organ Procurement and Transplantation Network (OPTN) that directs the allocation of organs to the sickest patients first without regard to a host of medical, geographic, and social factors that members of the transplant community view as an essential part of a sound organ allocation policy. Current organ allocation mechanisms are based on policies that reflect a broad consensus of medical experts and provide equal consideration for both the needs of the sickest patients and the efficient use of organs. This system also reduces potential waste of organs by minimizing cold ischemic time, increases access to transplantation for patients in local communities, provides positive incentives for local citizens and medical professionals to support organ donation initiatives, and decreases the cost of organ transplantation. Representatives of the American Society of Transplant Surgeons have testified before Congress that “giving priority to the sickest patients first over broad geographic areas would be wasteful and dangerous, resulting in fewer patients transplanted, increased death rates, increased retransplantation due to poor organ function, and increased overall cost of transplantation.” In response, Congress enacted a 1-year moratorium on the implementation of the HHS rule and provided for a study of the current organ allocation policy and HHS regulation by The Institute of Medicine. PMID:21845113

A simple prediction score for developing a hospital-acquired infection after acute ischemic stroke.

PubMed

Friedant, Adam J; Gouse, Brittany M; Boehme, Amelia K; Siegler, James E; Albright, Karen C; Monlezun, Dominique J; George, Alexander J; Beasley, Timothy Mark; Martin-Schild, Sheryl

2015-03-01

Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality in acute ischemic stroke patients. Although prior scoring systems have been developed to predict pneumonia in ischemic stroke patients, these scores were not designed to predict other infections. We sought to develop a simple scoring system for any HAI. Patients admitted to our stroke center (July 2008-June 2012) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time from symptom onset, or delay from symptom onset to hospital arrival greater than 48 hours. Infections were diagnosed via clinical, laboratory, and imaging modalities using standard definitions. A scoring system was created to predict infections based on baseline patient characteristics. Of 568 patients, 84 (14.8%) developed an infection during their stays. Patients who developed infection were older (73 versus 64, P < .0001), more frequently diabetic (43.9% versus 29.1%, P = .0077), and had more severe strokes on admission (National Institutes of Health Stroke Scale [NIHSS] score 12 versus 5, P < .0001). Ranging from 0 to 7, the overall infection score consists of age 70 years or more (1 point), history of diabetes (1 point), and NIHSS score (0-4 conferred 0 points, 5-15 conferred 3 points, >15 conferred 5 points). Patients with an infection score of 4 or more were at 5 times greater odds of developing an infection (odds ratio, 5.67; 95% confidence interval, 3.28-9.81; P < .0001). In our sample, clinical, laboratory, and imaging information available at admission identified patients at risk for infections during their acute hospitalizations. If validated in other populations, this score could assist providers in predicting infections after ischemic stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Stroke After Radiation Therapy for Head and Neck Cancer: What Is the Risk?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arthurs, Erin; Hanna, Timothy P.; Department of Oncology, Queen's University, Kingston, Ontario

Purpose: A retrospective population-based cohort study was conducted to determine the risk of ischemic stroke with respect to time, associated with curative radiation therapy in head and neck squamous cell carcinomas (HNSCC). Methods and Materials: On the basis of data from the Ontario Cancer Registry and regional cancer treatment centers, 14,069 patients were identified with diagnoses of squamous cell carcinoma of the oral cavity, larynx, and pharynx who were treated for cure between 1990 and 2010. Hazards of stroke and time to stroke were examined, accounting for the competing risk of death. Stroke risk factors identified through diagnostic and proceduralmore » administrative codes were adjusted for in the comparison between treatment regimens, which included surgery alone versus radiation therapy alone and surgery alone versus any exposure to radiation therapy. Results: Overall, 6% of patients experienced an ischemic stroke after treatment, with 5% experiencing a stroke after surgery, 8% after radiation therapy alone, and 6% after any exposure to radiation therapy. The cause-specific hazard ratios of ischemic stroke after radiation therapy alone and after any exposure to radiation therapy compared with surgery were 1.70 (95% confidence interval [CI]: 1.41-2.05) and 1.46 (95% CI: 1.23-1.73), respectively, after adjustment for stroke risk factors, patient factors, and disease-related factors. Conclusions: Radiation therapy was associated with an increased risk of ischemic stroke compared with surgery alone: for both radiation therapy alone and after all treatment modalities that included any radiation treatment were combined. Because of a shift toward a younger HNSCC patient population, our results speak to the need for adequate follow-up and survivorship care among patients who have been treated with radiation therapy. Advances in treatment that minimize chronic morbidity also require further evaluation.« less

Timing of gangrene tissue debridement after autologous bone marrow cell implantation in patients with superficial femoral arterial occlusion: preliminary experiences.

PubMed

Wang, C H; Lan, Y J; Yeh, C H; Ng, Y T; Chung, P V H; Hsu, C M; Kuo, L T; Huang, R E; Liu, M H; Cherng, W J

2012-08-01

Although implantation of bone marrow mononuclear cells (BMI) was shown to improve outcomes in patients with severe peripheral arterial occlusive disease (PAOD), little experience has been reported in patients with an arterial occlusion level above the knee, ischemic gangrene, and high cardiovascular risk. This study sought to investigate the timing of gangrene tissue debridement and the safety of BMI in these patients. Six "no-option" PAOD patients were enrolled with an arterial occlusion level above the knee, ischemic gangrene, and 3 systemic diseases related to a high cardiovascular risk. The ischemic status was evaluated by measuring the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and wound healing after BMI. All patients safely underwent the procedures with intravenous general anesthesia by titrating propofol. Major lower extremity amputation, minor debridement amputation, and debridement surgery were performed in 2 (33.3%), 1 (16.7%), and 2 (33.3%) patients, respectively, 3.1 2.8 months after BMI. Compared to the amputation group (N=3), the salvage group (N=3) had a significantly higher baseline ABI (P=0.02) and a shorter distance between the gangrene site and arterial occlusion site (P=0.01). In the 3 patients who underwent debridement, ABI and TcPO2 significantly improved 1 month after BMI, and gangrenous tissues were debrided 3.8 ± 3.6 (range, 1~8) months after BMI with complete healing within 1 month. Autologous BMI therapy is safe in patients at high cardiovascular risk with an arterial occlusion level above the knee and ischemic gangrene. Effective predictors of BMI include the baseline ABI and distance to the ischemia. Gangrene tissue should be debrided at least 1 month after BMI.

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

PubMed

Lee, Keon-Joo; Kim, Beom Joon; Han, Moon-Ku; Kim, Joon-Tae; Cho, Ki-Hyun; Shin, Dong-Ick; Yeo, Min-Ju; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Oh, Mi-Sun; Yu, Kyung-Ho; Lee, Byung-Chul; Hong, Keun-Sik; Cho, Yong-Jin; Choi, Jay Chol; Sohn, Sung Il; Hong, Jeong-Ho; Park, Tai Hwan; Park, Sang-Soon; Kwon, Jee-Hyun; Kim, Wook-Joo; Lee, Jun; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B; Bae, Hee-Joon

2018-01-01

This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P =0.004) and secondary ( P <0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant ( P <0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters. © 2017 American Heart Association, Inc.

Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation.

PubMed

Baste, Jean-Marc; Gay, Arnaud; Smail, Hassiba; Noël, Romain; Bubenheim, Michael; Begueret, Hugues; Morin, Jean-Paul; Litzler, Pierre-Yves

2015-01-01

Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture. A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours). No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion. The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults.

Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke.

PubMed

Pirici, Daniel; Pirici, Ionica; Mogoanta, Laurentiu; Margaritescu, Otilia; Tudorica, Valerica; Margaritescu, Claudiu; Ion, Daniela A; Simionescu, Cristiana; Coconu, Marieta

2012-10-01

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology. © 2011 Japanese Society of Neuropathology.

Myocardial imaging with 99mTc-Tetrofosmin: Influence of post-stress acquisition time, regional radiotracer uptake, and wall motion abnormalities on the clinical result.

PubMed

Giorgetti, Assuero; Kusch, Annette; Casagranda, Mirta; Tagliavia, Irene D'Aragona; Marzullo, Paolo

2010-04-01

We previously demonstrated that early (15', T1) post-stress myocardial imaging with Tetrofosmin could be more accurate than standard acquisitions (45', T2) in identifying coronary artery disease. To clarify this phenomenon, 120 subjects (age 61 +/- 10 years) with both T1 and T2 scans were divided into Group 1 (53/120 pts) with more ischemia at T1 vs T2 imaging (T1-T2SDS > or = 3); Group 2 (67/120 pts) with similar results (T1-T2SDS < or = 2). Myocardial areas were categorized as control nonischemic, ischemic, and scarred on the basis of perfusion/contraction properties and coronary anatomy. In each area, regional myocardial count statistic and semiquantitative wall motion/thickening values were obtained. Analysis of T1 and T2 post-stress myocardial counts demonstrated a significant Tetrofosmin wash-out rate that was higher in Group 1 control nonischemic regions (15 +/- 8% vs 13.6 +/- 9.6%, P < .02), significantly lower in Group 1 ischemic regions (7 +/- 10% vs 12.2 +/- 9.5%, P < .0001), and comparable between scarred areas of the two groups (P = NS). Delta post-stress wall thickening (T1-T2) was lower in Group 1 ischemic regions (-4.5 +/- 9.15% vs -1.90 +/- 7.0%, P < .001) and comparable in both control nonischemic and scarred areas of the two groups (P = NS). The clinical result of Tetrofosmin gated-SPECT can be influenced by the post-stress acquisition time because of ischemic-induced regional wall thickening abnormalities and the existence of a differential radiotracer myocardial wash-out.

Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: Selecting the optimal outcomes and statistical power for multi-centre preclinical trials

PubMed Central

Churilov, Leonid; Sidon, T. Kate; Aleksoska, Elena; Cox, Susan F.; Macleod, Malcolm R.; Howells, David W.

2017-01-01

Key disparities between the timing and methods of assessment in animal stroke studies and clinical trial may be part of the reason for the failure to translate promising findings. This study investigates the development of ischemic damage after thread occlusion MCAo in the rat, using histological and behavioural outcomes. Using the adhesive removal test we investigate the longevity of behavioural deficit after ischemic stroke in rats, and examine the practicality of using such measures as the primary outcome for future studies. Ischemic stroke was induced in 132 Spontaneously Hypertensive Rats which were assessed for behavioural and histological deficits at 1, 3, 7, 14, 21, 28 days, 12 and 24 weeks (n>11 per timepoint). The basic behavioural score confirmed induction of stroke, with deficits specific to stroke animals. Within 7 days, these deficits resolved in 50% of animals. The adhesive removal test revealed contralateral neglect for up to 6 months following stroke. Sample size calculations to facilitate the use of this test as the primary experimental outcome resulted in cohort sizes much larger than are the norm for experimental studies. Histological damage progressed from a necrotic infarct to a hypercellular area that cleared to leave a fluid filled cavity. Whilst absolute volume of damage changed over time, when corrected for changes in hemispheric volume, an equivalent area of damage was lost at all timepoints. Using behavioural measures at chronic timepoints presents significant challenges to the basic science community in terms of the large number of animals required and the practicalities associated with this. Multicentre preclinical randomised controlled trials as advocated by the MultiPART consortium may be the only practical way to deal with this issue. PMID:28182727

Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina.

PubMed

Greenberg, Barry H; Chou, Willis; Saikali, Khalil G; Escandón, Rafael; Lee, Jacqueline H; Chen, Michael M; Treshkur, Tatyana; Megreladze, Irakli; Wasserman, Scott M; Eisenberg, Paul; Malik, Fady I; Wolff, Andrew A; Shaburishvili, Tamaz

2015-01-01

The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in patients with ischemic cardiomyopathy and angina. These patients may have increased vulnerability to prolongation of the systolic ejection time. Omecamtiv mecarbil is a selective cardiac myosin activator that augments cardiac contractility in patients with systolic heart failure through a dose-dependent increase in systolic ejection time. In this double-blind, placebo-controlled study, patients with chronic heart failure were randomized 2:1 to receive omecamtiv mecarbil or placebo in 2 sequential cohorts of escalating doses designed to achieve plasma concentrations previously shown to increase systolic function. Patients underwent 2 symptom-limited exercise treadmill tests (ETTs) at baseline (ETT1 and ETT2) and again before the end of a 20-h infusion of omecamtiv mecarbil (ETT3). The primary pre-defined safety endpoint (i.e., the proportion of patients who stopped ETT3 because of angina at a stage earlier than baseline) was observed in 1 patient receiving placebo and none receiving omecamtiv mecarbil. No dose-dependent differences emerged in the proportion of patients stopping ETT3 for any reason or in the pattern of adverse events. Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality.

PubMed

Schmidt, Morten; Hováth-Puhó, Erzsébet; Christiansen, Christian Fynbo; Petersen, Karin L; Bøtker, Hans Erik; Sørensen, Henrik Toft

2014-11-25

To examine whether preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. We conducted a nationwide population-based cohort study. Using medical databases, we identified all first-time stroke hospitalizations in Denmark between 2004 and 2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current (prescription redemption within 60 days before hospital admission), former, and nonuse. Current use was further classified as new or long-term use. Cox regression was used to compute hazard ratios (HRs) of death within 30 days, controlling for potential confounding through multivariable adjustment and propensity score matching. The adjusted HR of death for ischemic stroke was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2 inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score-matched analysis supported the association between older COX-2 inhibitors and ischemic stroke mortality. There was no association for former users. Mortality from intracerebral hemorrhage was not associated with use of nonselective NSAIDs or COX-2 inhibitors. Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not associated with mortality from ischemic stroke or intracerebral hemorrhage. © 2014 American Academy of Neurology.

Change in blood pressure variability in patients with acute ischemic stroke and its effect on early neurologic outcome

PubMed Central

Hong, Jeong-Ho; Jang, Min Uk; Choi, Nack Cheon; Lee, Ji Sung; Kim, Beom Joon; Han, Moon-Ku; Bae, Hee-Joon

2017-01-01

Background How short-term blood pressure variability (BPV) is affected in the acute stage of ischemic stroke and whether BPV is associated with early neurologic outcomes remains unclear. Methods Patients who admitted for ischemic stroke within 24 h of symptom onset were consecutively identified between January 2010 and January 2015. BP profiles measured in real-time were summarized into short-term, 24-h time intervals, based on standard deviation (SD) and mean of systolic BP (SBPSD) during the first 3 days. The primary outcome was daily assessment of early neurological deterioration (END). The associations between short-term SBPSD values and the secular trend for primary outcome were examined. Results A total of 2,545 subjects (mean age, 67.1 ± 13.5 years old and median baseline National Institutes of Health Stroke Scale score, 3) arrived at the hospital an average of 6.1 ± 6.6 h after symptom onset. SBPSD values at day 1 (SD#D1), SD#D2, and SD#D3 were 14.4 ± 5.0, 12.5 ± 4.5, and 12.2 ± 4.6 mmHg, respectively. Multivariable analyses showed that SD#D2 was independently associated with onset of END at day 2 (adjusted odds ratio, 1.08; 95% confidence interval, 1.03–1.13), and SD#D3 was independently associated with END#D3 (1.07, 1.01–1.14), with adjustments for predetermined covariates, SBPmean, and interactions with daily SBPSD. Conclusion Short-term BPV changed and stabilized from the first day of ischemic stroke. Daily high BPV may be associated with neurological deterioration independent of BPV on the previous day. PMID:29252991

Bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes versus cold-knife transurethral incision for the treatment of posterior urethral stricture: a prospective, randomized study.

PubMed

Cai, Wansong; Chen, Zhiyuan; Wen, Liping; Jiang, Xiangxin; Liu, Xiuheng

2016-01-01

Evaluate the efficiency and safety of bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes for the treatment of posterior urethral stricture. Compare the outcomes following bipolar plasma vaporization with conventional cold-knife urethrotomy. A randomized trial was performed to compare patient outcomes from the bipolar and cold-knife groups. All patients were assessed at 6 and 12 months postoperatively via urethrography and uroflowmetry. At the end of the first postoperative year, ureteroscopy was performed to evaluate the efficacy of the procedure. The mean follow-up time was 13.9 months (range: 12 to 21 months). If re-stenosis was not identified by both urethrography and ureteroscopy, the procedure was considered "successful". Fifty-three male patients with posterior urethral strictures were selected and randomly divided into two groups: bipolar group (n=27) or cold-knife group (n=26). Patients in the bipolar group experienced a shorter operative time compared to the cold-knife group (23.45±7.64 hours vs 33.45±5.45 hours, respectively). The 12-month postoperative Qmax was faster in the bipolar group than in the cold-knife group (15.54±2.78 ml/sec vs 18.25±2.12 ml/sec, respectively). In the bipolar group, the recurrence-free rate was 81.5% at a mean follow-up time of 13.9 months. In the cold-knife group, the recurrence-free rate was 53.8%. The application of bipolar plasma-cutting and plasma-loop electrodes for the management of urethral stricture disease is a safe and reliable method that minimizes the morbidity of urethral stricture resection. The advantages include a lower recurrence rate and shorter operative time compared to the cold-knife technique.

Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry.

PubMed

Saito, Takuro; Gotoh, Mitsukazu; Satomi, Susumu; Uemoto, Shinji; Kenmochi, Takashi; Itoh, Toshinori; Kuroda, Yoshikazu; Yasunami, Youichi; Matsumoto, Shnichi; Teraoka, Satoshi

2010-10-15

This report summarizes outcomes of islet transplantation employing donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan Islet Transplantation Registry. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus, including two patients who had prior kidney transplantation. All but one donor (64/65) was DCD at the time of harvesting. Factors influencing criteria for islet release included duration of low blood pressure of the donor, cold ischemic time, and usage of Kyoto solution for preservation. Multivariate analysis selected usage of Kyoto solution as most important. Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survival defined as C-peptide level more than or equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years, respectively, whereas corresponding graft survival after multiple transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients remained free of severe hypoglycemia while three achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients. Islet transplantation employing DCD can ameliorate severe hypoglycemic episodes, significantly improve HbA1c levels, sustain significant levels of C-peptide, and achieve insulin independence after multiple transplantations. Thus, DCD can be an important resource for islet transplantation if used under strict releasing criteria and in multiple transplantations, particularly in countries where heart-beating donors are not readily available.

Dynamics of myelin content decrease in the rat stroke model

NASA Astrophysics Data System (ADS)

Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

2017-08-01

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

Expression analysis of genes involved in TLR2-related signaling pathway: Inflammation and apoptosis after ischemic brain injury.

PubMed

Winters, L; Winters, T; Gorup, D; Mitrečić, D; Curlin, M; Križ, J; Gajović, S

2013-05-15

Toll-like receptor 2 (TLR2) is involved in innate immunity in the brain and in the cascade of events after ischemic stroke. The aim of this study was to get an insight into the expression of genes related to TLR2 signaling pathway and associated with inflammation and apoptosis in the later stages of brain response after ischemic injury. Middle cerebral artery occlusion was performed on both wild-type and TLR2(-/-) mice followed by real-time PCR to measure the relative expression of selected genes. In TLR2(-/-) mice expression of genes involved in proinflammatory response was decreased after cerebral ischemia. Tnf was the most prominent cytokine active in the late phase of recovery. Contrary to proinflammatory genes, the expression of Casp8, as a hallmark of apoptosis, was increased in TLR2(-/-) mice, in particular in the late phase of recovery. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

Athletics, minor trauma, and pediatric arterial ischemic stroke.

PubMed

Sepelyak, Kathryn; Gailloud, Philippe; Jordan, Lori C

2010-05-01

Pediatric arterial ischemic stroke may occur as the result of trivial head or neck trauma sustained during a sports activity. We describe three cases of sports-related stroke in previously healthy school-age children and discuss acute and long-term stroke care. Possible mechanisms of sports-related stroke are addressed, as is evaluation for cause of stroke in children. In one of the reported cases, the child was found to have a vertebral artery dissection as the cause of his stroke, but no definitive cause of stroke was identified in the other two cases despite extensive evaluation. The advisability and timing of returning to athletic activities after stroke is also discussed. Many children with sports-related stroke are initially seen by a sports trainer, a pediatrician, or an ER physician. Thus, it is particularly important that these professionals are aware of the possibility of ischemic stroke occurring after even mild athletic injury. Childhood stroke may result from injuries sustained during athletic activities and should be considered when a child has acute focal neurologic signs.

Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain*

PubMed Central

Hou, Sheng Tao; Jiang, Susan X.; Zaharia, L. Irina; Han, Xiumei; Benson, Chantel L.; Slinn, Jacqueline; Abrams, Suzanne R.

2016-01-01

Phaseic acid (PA) is a phytohormone regulating important physiological functions in higher plants. Here, we show the presence of naturally occurring (−)-PA in mouse and rat brains. (−)-PA is exclusively present in the choroid plexus and the cerebral vascular endothelial cells. Purified (−)-PA has no toxicity and protects cultured cortical neurons against glutamate toxicity through reversible inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery elicited a significant induction in (−)-PA expression in the cerebrospinal fluid but not in the peripheral blood. Importantly, (−)-PA induction only occurred in the penumbra area, indicting a protective role of PA in the brain. Indeed, elevating the (−)-PA level in the brain reduced ischemic brain injury, whereas reducing the (−)-PA level using a monoclonal antibody against (−)-PA increased ischemic injury. Collectively, these studies showed for the first time that (−)-PA is an endogenous neuroprotective molecule capable of reversibly inhibiting glutamate receptors during ischemic brain injury. PMID:27864367

Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain.

PubMed

Hou, Sheng Tao; Jiang, Susan X; Zaharia, L Irina; Han, Xiumei; Benson, Chantel L; Slinn, Jacqueline; Abrams, Suzanne R

2016-12-30

Phaseic acid (PA) is a phytohormone regulating important physiological functions in higher plants. Here, we show the presence of naturally occurring (-)-PA in mouse and rat brains. (-)-PA is exclusively present in the choroid plexus and the cerebral vascular endothelial cells. Purified (-)-PA has no toxicity and protects cultured cortical neurons against glutamate toxicity through reversible inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery elicited a significant induction in (-)-PA expression in the cerebrospinal fluid but not in the peripheral blood. Importantly, (-)-PA induction only occurred in the penumbra area, indicting a protective role of PA in the brain. Indeed, elevating the (-)-PA level in the brain reduced ischemic brain injury, whereas reducing the (-)-PA level using a monoclonal antibody against (-)-PA increased ischemic injury. Collectively, these studies showed for the first time that (-)-PA is an endogenous neuroprotective molecule capable of reversibly inhibiting glutamate receptors during ischemic brain injury. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke

PubMed Central

Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Castellanos, Mar; Blanco, Miguel; Rodríguez-Yáñez, Manuel; Serena, Joaquín; Leira, Rogelio; Castillo, José

2011-01-01

The capacity of the blood enzyme glutamate oxaloacetate transaminase (GOT) to remove glutamate from the brain by means of blood glutamate degradation has been shown in experimental models to be an efficient and novel neuroprotective tool against ischemic stroke; however, the beneficial effects of this enzyme should be tested in patients with stroke to validate these results. This study aims to investigate the association of GOT levels in blood with clinical outcome in patients with acute ischemic stroke. In two clinical independent studies, we found that patients with poor outcome show higher glutamate and lower GOT levels in blood at the time of admission. Lower GOT levels and higher glutamate levels were independently associated with poorer functional outcome at 3 months and higher infarct volume. These findings show a clear association between high blood glutamate levels and worse outcome and vice versa for GOT, presumably explained by the capacity of this enzyme to metabolize blood glutamate. PMID:21266984

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

PubMed

Barsic, Bruno; Dickerman, Stuart; Krajinovic, Vladimir; Pappas, Paul; Altclas, Javier; Carosi, Giampiero; Casabé, José H; Chu, Vivian H; Delahaye, Francois; Edathodu, Jameela; Fortes, Claudio Querido; Olaison, Lars; Pangercic, Ana; Patel, Mukesh; Rudez, Igor; Tamin, Syahidah Syed; Vincelj, Josip; Bayer, Arnold S; Wang, Andrew

2013-01-01

The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

The role of cold cues at different life stages on germination and flowering phenology.

PubMed

Rubin, Matthew J; Friedman, Jannice

2018-04-23

The timing of major phenological transitions is critical to lifetime fitness, and life history theory predicts differences for annual and perennial plants. To correctly time these transitions, many plants rely on environmental cues such as exposure to extended periods of cold, which may occur at different stages throughout their lifetime. We studied the role of cold at different life stages, by jointly exposing seed (stratification) and rosettes (vernalization) to cold. We used 23 populations of Mimulus guttatus, which vary from annuals to perennials, and investigated how cold at one or both stages affected germination, flowering, growth, and biomass. We found that stratification and vernalization interact to affect life cycle transitions, and that cold at either stage could synchronize flowering phenology. For perennials, either stratification or vernalization is necessary for maximum flowering. We also found that germination timing covaried with later traits. Moreover, plants from environments with dissimilar climates displayed different phenological responses to stratification or vernalization. In general, cold is more important for seed germination in annuals and plants from environments with warm temperatures and variable precipitation. In contrast, cold is more important for flowering in perennials: it accelerates flowering in plants from lower precipitation environments, and it increases flowering proportion in plants from cooler, more stable precipitation environments. We discuss our findings in the context of the variable environments plants experience within a population and the variation encountered across the biogeographic native range of the species. © 2018 Botanical Society of America.

Ischemia episode detection in ECG using kernel density estimation, support vector machine and feature selection

PubMed Central

2012-01-01

Background Myocardial ischemia can be developed into more serious diseases. Early Detection of the ischemic syndrome in electrocardiogram (ECG) more accurately and automatically can prevent it from developing into a catastrophic disease. To this end, we propose a new method, which employs wavelets and simple feature selection. Methods For training and testing, the European ST-T database is used, which is comprised of 367 ischemic ST episodes in 90 records. We first remove baseline wandering, and detect time positions of QRS complexes by a method based on the discrete wavelet transform. Next, for each heart beat, we extract three features which can be used for differentiating ST episodes from normal: 1) the area between QRS offset and T-peak points, 2) the normalized and signed sum from QRS offset to effective zero voltage point, and 3) the slope from QRS onset to offset point. We average the feature values for successive five beats to reduce effects of outliers. Finally we apply classifiers to those features. Results We evaluated the algorithm by kernel density estimation (KDE) and support vector machine (SVM) methods. Sensitivity and specificity for KDE were 0.939 and 0.912, respectively. The KDE classifier detects 349 ischemic ST episodes out of total 367 ST episodes. Sensitivity and specificity of SVM were 0.941 and 0.923, respectively. The SVM classifier detects 355 ischemic ST episodes. Conclusions We proposed a new method for detecting ischemia in ECG. It contains signal processing techniques of removing baseline wandering and detecting time positions of QRS complexes by discrete wavelet transform, and feature extraction from morphology of ECG waveforms explicitly. It was shown that the number of selected features were sufficient to discriminate ischemic ST episodes from the normal ones. We also showed how the proposed KDE classifier can automatically select kernel bandwidths, meaning that the algorithm does not require any numerical values of the parameters to be supplied in advance. In the case of the SVM classifier, one has to select a single parameter. PMID:22703641

Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

PubMed

Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

2013-11-01

The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

Effect of using fluoxetine at different time windows on neurological functional prognosis after ischemic stroke.

PubMed

Guo, Yi; He, Yitao; Tang, Bingshan; Ma, Kefu; Cai, Zhili; Zeng, Siling; Zhang, Ying; Jiang, Xin

2016-01-01

To evaluate the effect of using fluoxetine at different time intervals after ischemic stroke on neurological functional prognosis in China. The patients enrolled were randomly allocated to three groups. Group A received fluoxetine 20 mg/day immediately; group B received fluoxetine 20 mg/day 7 days after enrollment; and group C did not receive fluoxetine. The therapeutic duration of fluoxetine was 90 days and the follow-up period was 180 days. The mean NIHSS score at day 90 was significantly lower in group A than group C (P = 0.005), while at day 180, the mean score in group A was significantly lower than groups B and C (P = 0.035, P = 0.000), respectively. The mean BI score at day 90 was significantly higher in group A than group C (P = 0.001), while at day 180, the mean score in group A was significantly higher than groups B and C (P = 0.036, P = 0.000), respectively. Regression analysis indicated that lower NIHSS score and higher BI score at day 180 were attributed to the early administration of fluoxetine. In patients with ischemic stroke, early administration of fluoxetine may improve the neurological functional prognosis.

Functional reorganization of visual cortex maps after ischemic lesions is accompanied by changes in expression of cytoskeletal proteins and NMDA and GABA(A) receptor subunits.

PubMed

Zepeda, Angelica; Sengpiel, Frank; Guagnelli, Miguel Angel; Vaca, Luis; Arias, Clorinda

2004-02-25

Reorganization of cortical representations after focal visual cortex lesions has been documented. It has been suggested that functional reorganization may rely on cellular mechanisms involving modifications in the excitatory/inhibitory neurotransmission balance and on morphological changes of neurons peripheral to the lesion. We explored functional reorganization of cortical retinotopic maps after a focal ischemic lesion in primary visual cortex of kittens using optical imaging of intrinsic signals. After 1, 2, and 5 weeks postlesion (wPL), we addressed whether functional reorganization correlated in time with changes in the expression of MAP-2, GAP-43, GFAP, GABA(A) receptor subunit alpha1 (GABA(A)alpha1), subunit 1 of the NMDA receptor (NMDAR1), and in neurotransmitter levels at the border of the lesion. Our results show that: (1) retinotopic maps reorganize with time after an ischemic lesion; (2) MAP-2 levels increase gradually from 1wPL to 5wPL; (3) MAP-2 upregulation is associated with an increase in dendritic-like structures surrounding the lesion and a decrease in GFAP-positive cells; (4) GAP-43 levels reach the highest point at 2wPL; (5) NMDAR1 and glutamate contents increase in parallel from 1wPL to 5wPL; (6) GABA(A)alpha1 levels increase from 1wPL to 2wPL but do not change after this time point; and (7) GABA contents remain low from 1wPL to 5wPL. This is a comprehensive study showing for the first time that functional reorganization correlates in time with dendritic sprouting and with changes in the excitatory/inhibitory neurotransmission systems previously proposed to participate in cortical remodeling and suggests mechanisms by which plasticity of cortical representations may occur.

Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.

PubMed

Beker, Mustafa Caglar; Caglayan, Berrak; Yalcin, Esra; Caglayan, Ahmet Burak; Turkseven, Seyma; Gurel, Busra; Kelestemur, Taha; Sertel, Elif; Sahin, Zafer; Kutlu, Selim; Kilic, Ulkan; Baykal, Ahmet Tarik; Kilic, Ertugrul

2018-03-01

Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools. Here, we present evidence that midnight (ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct volume, brain swelling, neurological deficit score, neuronal survival, and decreased apoptotic cell death compared with ischemia induced at other time points, which were associated with increased expressions of circadian proteins Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover, ribosomal protein S6, mTOR, and Bad were also significantly increased, while the levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were decreased at this time point compared to ZT0 (06:00). Furthermore, detailed proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared with early morning. Our results indicate that nighttime I/R injury results in less severe neuronal damage, with increased neuronal survival, increased levels of survival kinases and circadian clock proteins, and also alters the circadian-related proteins.

Inside The Cold War. A Cold Warrior’s Reflections

DTIC Science & Technology

1999-09-01

years . Downsizing after such a lengthy time was very painful because, for the first time in our recent history , everyone in uniform was a volunteer...Commendation Medal w/30LCs, and the Combat Crew Medal. When he retired from active duty in February 1983, Chris Adams became associate director of Los Alamos ...respective countries faithfully during those critical years of roller coaster politics, inconsistent diplomacy, and occasional lunacy. The Cold

Convective Cold Pool Structure and Boundary Layer Recovery in DYNAMO

NASA Astrophysics Data System (ADS)

Savarin, A.; Chen, S. S.; Kerns, B. W.; Lee, C.; Jorgensen, D. P.

2012-12-01

One of the key factors controlling convective cloud systems in the Madden-Julian Oscillation (MJO) over the tropical Indian Ocean is the property of the atmospheric boundary layer. Convective downdrafts and precipitation from the cloud systems produce cold pools in the boundary layer, which can inhibit subsequent development of convection. The recovery time is the time it takes for the boundary layer to return to pre convective conditions. It may affect the variability of the convection on various time scales during the initiation of MJO. This study examines the convective cold pool structure and boundary layer recovery using the NOAA WP-3D aircraft observations, include the flight-level, Doppler radar, and GPS dropsonde data, collected during the Dynamics of MJO (DYNAMO) field campaign from November-December 2011. The depth and strength of convective cold pools are defined by the negative buoyancy, which can be computed from the dropsonde data. Convective downdraft can be affected by environmental water vapor due to entrainment. Mid-level dry air observed during the convectively suppressed phase of MJO seems to enhance convective downdraft, making the cold pools stronger and deeper. Recovery of the cold pools in the boundary layer is determined by the strength and depth of the cold pools and also the air-sea heat and moisture fluxes. Given that the water vapor and surface winds are distinct for the convectively active and suppressed phases of MJO over the Indian Ocean, the aircraft data are stratified by the two different large-scale regimes of MJO. Preliminary results show that the strength and depth of the cold pools are inversely correlated with the surrounding mid-level moisture. During the convectively suppressed phase, the recovery time is ~5-20 hours in relative weak wind condition with small air-sea fluxes. The recovery time is generally less than 6 hours during the active phase of MJO with moist mid-levels and stronger surface wind and air-sea fluxes.

Transient ischemic attack

MedlinePlus

... artery surgery - discharge Stroke - discharge Taking warfarin (Coumadin) Images Endarterectomy Transient Ischemic attack (TIA) References Biller J, Ruland S, Schneck MJ. Ischemic cerebrovascular disease. In Daroff ...

Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia

PubMed Central

Kim, In Hye; Jeon, Yong Hwan; Lee, Tae-Kyeong; Cho, Jeong Hwi; Lee, Jae-Chul; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Bich-Na; Kim, Yang Hee; Hong, Seongkweon; Yan, Bing Chun; Won, Moo-Ho; Lee, Yun Lyul

2017-01-01

Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning (2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult (5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity. PMID:28761424

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

PubMed

d'Esterre, Christopher D; Boesen, Mari E; Ahn, Seong Hwan; Pordeli, Pooneh; Najm, Mohamed; Minhas, Priyanka; Davari, Paniz; Fainardi, Enrico; Rubiera, Marta; Khaw, Alexander V; Zini, Andrea; Frayne, Richard; Hill, Michael D; Demchuk, Andrew M; Sajobi, Tolulope T; Forkert, Nils D; Goyal, Mayank; Lee, Ting Y; Menon, Bijoy K

2015-12-01

Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion. © 2015 American Heart Association, Inc.

The effect of some heat treatment parameters on the dimensional stability of AISI D2

NASA Astrophysics Data System (ADS)

Surberg, Cord Henrik; Stratton, Paul; Lingenhöle, Klaus

2008-01-01

The tool steel AISI D2 is usually processed by vacuum hardening followed by multiple tempering cycles. It has been suggested that a deep cold treatment in between the hardening and tempering processes could reduce processing time and improve the final properties and dimensional stability. Hardened blocks were then subjected to various combinations of single and multiple tempering steps (520 and 540 °C) and deep cold treatments (-90, -120 and -150 °C). The greatest dimensional stability was achieved by deep cold treatments at the lowest temperature used and was independent of the deep cold treatment time.

Association of ALOX5AP with ischemic stroke: a population-based case-control study.

PubMed

Kaushal, Ritesh; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Flaherty, Matthew; Moomaw, Charles; Sekar, Padmini; Kissela, Brett; Kleindorfer, Dawn; Chakraborty, Ranajit; Broderick, Joseph; Deka, Ranjan; Woo, Daniel

2007-06-01

Arachidonate 5-lipoxygenase activating protein (ALOX5AP) has been reported to demonstrate linkage and association with ischemic stroke and myocardial infarction. However, replication studies have been conflicting and to date, a significant proportion of blacks have not been studied. We prospectively recruited cases of ischemic stroke from all 16 hospitals in the Greater Cincinnati/Northern Kentucky region and demographically matched them to stroke-free population-based controls. Single nucleotide polymorphisms (SNPs) were selected based on association with ischemic stroke in prior studies. Allelic, genotypic and haplotypic association testing was performed using HAPLOVIEW. Multiple logistic regression was used to control for the presence of traditional risk factors including hypertension, diabetes, hypercholesterolemia and smoking. A total of 357 cases and 482 controls were genotyped. The SNPs, rs9579646 and rs4769874 were found to be significantly associated at both allelic (P=0.019 and P<10(-4), respectively) and genotypic level with ischemic stroke among whites after correction for multiple testing. Haplotype association was identified with ischemic stroke as well as ischemic stroke subtypes among whites. Although an overall haplotype association with ischemic stroke was identified among blacks no evidence of association among individual haplotypes, alleles or genotypes were observed. Allele frequencies for the SNPs examined were markedly different among whites and blacks. In conclusion, we report significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites. No significant association was identified among blacks.

Fasting and non-fasting triglycerides and risk of ischemic cardiovascular disease in Japanese men and women: the Circulatory Risk in Communities Study (CIRCS).

PubMed

Iso, Hiroyasu; Imano, Hironori; Yamagishi, Kazumasa; Ohira, Tetsuya; Cui, Renzhe; Noda, Hiroyuki; Sato, Shinichi; Kiyama, Masahiko; Okada, Takeo; Hitsumoto, Shinichi; Tanigawa, Takeshi; Kitamura, Akihiko

2014-11-01

Non-fasting triglycerides were reported to have a greater impact on risk of ischemic cardiovascular events than fasting triglycerides. However, evidence from Asia, where the prevalence of dyslipidemia is generally lower, has been limited. We used 1975-1986 baseline surveys to investigate cohort data of 10,659 (4264 men and 6395 women) residents aged 40-69 years, initially free from ischemic heart disease and stroke, in four Japanese communities. Serum triglyceride concentrations at baseline were obtained for 2424 fasting (≥8 h after meal) and 8235 non-fasting (<8 h after meal) participants. During the 22-year follow-up, 284 (165 men and 119 women) developed ischemic heart disease and 666 (349 men and 317 women) ischemic stroke. After adjustment for age, sex and known cardiovascular risk factors, multivariable hazard ratios (95%CI) of ischemic cardiovascular disease (ischemic heart disease and ischemic stroke) for the highest versus lowest quartiles of triglycerides were 1.71 (1.14-2.59), P for trend = 0.013, for fasting participants and 1.60 (1.25-2.05), P for trend <0.001, for non-fasting participants. The positive associations did not differ between fasting and non-fasting men, while they were strong for non-fasting women. They were stronger for ischemic heart disease than for ischemic stroke. After further adjustment for HDL-cholesterol, these associations were slightly attenuated, but remained statistically significant. Non-fasting as well as fasting triglycerides are predictive of risk of ischemic cardiovascular disease for Japanese men, as are non-fasting triglycerides for women. Copyright © 2014. Published by Elsevier Ireland Ltd.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

PubMed

Bousser, M G; Amarenco, P; Chamorro, A; Fisher, M; Ford, I; Fox, K; Hennerici, M G; Mattle, H P; Rothwell, P M

2009-01-01

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event. Copyright 2009 S. Karger AG, Basel.

Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke

PubMed Central

Tuttolomondo, Antonino; Pecoraro, Rosaria; Casuccio, Alessandra; Di Raimondo, Domenico; Buttà, Carmelo; Clemente, Giuseppe; Corte, Vittoriano della; Guggino, Giuliana; Arnao, Valentina; Maida, Carlo; Simonetta, Irene; Maugeri, Rosario; Squatrito, Rosario; Pinto, Antonio

2015-01-01

Abstract CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtype We enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer. Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes. These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke. PMID:25997053

Neuroprotective Interventions: Is It Too Late?

PubMed Central

Jenkins, Dorothea; Chang, Eugene; Singh, Inderjit

2013-01-01

In most cases of neonatal hypoxic-ischemic encephalopathy, the exact timing of the hypoxic-ischemic event is unknown, and we have few reliable biomarkers to precisely identify the phase of injury or recovery in an individual patient. However, it is becoming increasingly clear that for neuroprotection in neonates to succeed, an understanding of the phase of injury is important to ascertain. In addition, in utero antecedents of chronic hypoxia, hypoxic preconditioning, intrauterine infection, and fetal gender may change the expected time course of injury. Neuroprotective interventions, such as hypothermia and N-acetylcysteine, currently have efficacy in human and animal studies only if instituted early in the inflammatory cascade. While these cascades are currently being investigated, molecular mechanisms of recovery have received little attention and may ultimately reveal a window for therapeutic intervention that is much longer than current paradigms. PMID:19745093

Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

PubMed

Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

2016-08-01

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

[Implementation of a regional system for the emergency care of acute ischemic stroke: Initial results].

PubMed

Soares-Oliveira, Miguel; Araújo, Fernando

2014-06-01

Implementing integrated systems for emergency care of patients with acute ischemic stroke helps reduce morbidity and mortality. We describe the process of organizing and implementing a regional system to cover around 3.7 million people and its main initial results. We performed a descriptive analysis of the implementation process and a retrospective analysis of the following parameters: number of patients prenotified by the pre-hospital system; number of times thrombolysis was performed; door-to-needle time; and functional assessment three months after stroke. The implementation process started in November 2005 and ended in December 2009, and included 11 health centers. There were 3574 prenotifications from the prehospital system. Thrombolysis was performed in 1142 patients. The percentage of patients receiving thrombolysis rose during the study period, with a maximum of 16%. Median door-to-needle time was 62 min in 2009. Functional recovery three months after stroke was total or near total in 50% of patients. The regional system implemented for emergency care of patients with acute ischemic stroke has led to health gains, with progressive improvements in patients' access to thrombolysis, and to greater equity in the health care system, thus helping to reduce mortality from cerebrovascular disease in Portugal. Our results, which are comparable with those of international studies, support the strategy adopted for implementation of this system. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Hydrophilic Polymer-associated Ischemic Enterocolitis.

PubMed

Chavez, Jesus A; Chen, Wei; Frankel, Wendy L; Arnold, Christina A

2017-02-01

Hydrophilic polymer coating of medical devices serves to lubricate the device and prevent device-related complications. The coating can be mechanically disrupted and result in downstream injury via presumed thromboembolism. This process has been reported in the brain, heart, lung, and skin, and has been replicated through animal studies and in vitro histologic processing of the polymer coating. We report the first description of hydrophilic polymer-associated ischemic enterocolitis in a series of 7 specimens (small bowel=2, colon=4, aortic thrombus=1) from 3 patients. We report a 4% incidence among all patients with an ischemic bowel resection between April 29, 2014 and August 8, 2016. All patients developed bowel ischemia within 1 day of aortic repair, and all bowel resection specimens showed polymers, mainly in the submucosal vessels in areas of extensive ischemia. The polymers appeared as basophilic, intravascular, serpiginous structures. In a patient who developed acute paralysis after the aortic repair, identical polymers were identified in the aortic thrombus and the ischemic bowel segment. We demonstrate that the polymers display an altered morphology over time and with various graft types, and that the degrading polymers are associated with a foreign body giant cell reaction. Special stains can aid in diagnosis, with the polymers turquoise on a colloidal iron stain, pink on von Kossa and mucicarmine stains, and pale blue on trichrome. Clinical follow-up was available up to 115 weeks: 1 patient died, and 2 are alive and well. In summary, we report a new diagnostic entity to be considered in the differential diagnosis of iatrogenic ischemic injuries in the gastrointestinal tract. Awareness of this entity is important to elucidate the cause of ischemia and to prevent misdiagnosis of the polymers and their associated giant cell reaction as a parasitic infection, granulomatous vasculitis, sarcoidosis, and idiopathic inflammatory bowel disease.

The synergetic effect of edaravone and borneol in the rat model of ischemic stroke.

PubMed

Wu, Hai-Yin; Tang, Ying; Gao, Li-Yan; Sun, Wei-Xiang; Hua, Yao; Yang, Shi-Bao; Zhang, Zheng-Ping; Liao, Gao-Yong; Zhou, Qi-Gang; Luo, Chun-Xia; Zhu, Dong-Ya

2014-10-05

Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two drugs in the rat model of transient cerebral ischemia. Edaravone scavenged OH, NO and ONOO─ concentration-dependently, and borneol inhibited ischemia/reperfusion-induced tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) expressions. In the rat model of transient cerebral ischemia and reperfusion, the combination of edaravone and borneol significantly ameliorated ischemic damage with an optimal proportion of 4:1. Emax (% inhibition) of edaravone, borneol and two drugs in combination was 55.7%, 65.8% and 74.3% respectively. ED50 of edaravone and borneol was 7.17 and 0.36 mg/kg respectively. When two drugs in combination, ED50 was 0.484 mg/kg, in which edaravone was 0.387 mg/kg (ineffective dose) and borneol was 0.097 mg/kg (ineffective dose). Combination index (CI)<1 among effects observed in experiments, suggesting a significant synergistic effect. Reduced levels of pro-inflammatory mediators and free radicals were probably associated with the synergistic effect of edaravone and borneol. The combination exhibited a therapeutic time window of 6h in ischemia/reperfusion model, and significantly ameliorated damages in permanent ischemia model. Moreover, two drugs in combination promoted long-term effect, including improved elemental vital signs, sensorimotor functions and spatial cognition. Our results suggest that the combination of edaravone and borneol have a synergistic effect for treating ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain-Derived Neurotrophic Factor Promotes Vasculature-Associated Migration of Neuronal Precursors toward the Ischemic Striatum

PubMed Central

Grade, Sofia; Weng, Yuan C.; Snapyan, Marina; Kriz, Jasna; Malva, João O.; Saghatelyan, Armen

2013-01-01

Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. PMID:23383048

Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.

PubMed

Gelderblom, Mathias; Melzer, Nico; Schattling, Benjamin; Göb, Eva; Hicking, Gordon; Arunachalam, Priyadharshini; Bittner, Stefan; Ufer, Friederike; Herrmann, Alexander M; Bernreuther, Christian; Glatzel, Markus; Gerloff, Christian; Kleinschnitz, Christoph; Meuth, Sven G; Friese, Manuel A; Magnus, Tim

2014-11-01

Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke. © 2014 American Heart Association, Inc.

Topical Administration of Oxygenated Hemoglobin Improved Wound Healing in an Ischemic Rabbit Ear Model.

PubMed

Xie, Ping; Jia, Shengxian; Tye, Ross; Xu, Wei; Zhong, Aimei; Hong, Seok J; Galiano, Robert D; Mustoe, Thomas A

2016-02-01

Localized oxygen deficiency plays a central role in the pathogenesis of chronic wounds; thus, rectifying localized ischemia with oxygen therapy has been postulated to be an integral aspect of the management of chronic wounds. The efficacy of a novel approach for oxygen therapy on chronic wound healing was evaluated. Oxygen was delivered to ischemic wounds by means of the topical application of oxygenated, chemically modified bovine hemoglobin (IKOR 2084) in a validated rabbit ear ischemic wound model. The wound healing was evaluated histologically by measuring epithelial gap and neo-granulation tissue area. In situ expression of endothelial cells (CD31) and proliferative cells (Ki-67) was examined by immunohistochemistry analysis. The mRNA of vascular endothelial growth factor, endothelial nitric oxide synthase, and matrix metalloproteinase-9 was quantified by real-time reverse-transcriptase polymerase chain reaction. The collagen was detected by Sirius red staining. In comparison with topical application of saline, the administration of oxygenated IKOR 2084 increases wound reepithelialization and formation of neo-granulation tissue in a dose-dependent manner, and cellular proliferation (Ki-67). Conversely, the administration of deoxygenated IKOR 2084 aggravated the ischemic wound healing process. Moreover, the topical administration of oxygenated IKOR 2084 induces angiogenesis as evidenced by concomitant increases in CD31 protein and vascular endothelial growth factor and endothelial nitric oxide synthase mRNA expression in treated wounds. Oxygenated IKOR 2084 administration also increased collagen deposition in wounds, with decreases in the expression of matrix metalloproteinase-9 mRNA. This study suggests that the topical application of oxygenated IKOR 2084 ameliorates the reparative progress of ischemic wounds through enhanced angiogenesis, cellular proliferation, and collagen deposition.

Enhanced peripheral dopamine impairs post-ischemic healing by suppressing angiotensin receptor type 1 expression in endothelial cells and inhibiting angiogenesis.

PubMed

Sarkar, Chandrani; Ganju, Ramesh K; Pompili, Vincent J; Chakroborty, Debanjan

2017-02-01

Increased circulating catecholamines have been linked with cardiovascular anomalies as well as with peripheral vascular diseases. Although the roles of epinephrine and norepinephrine have received considerable attention, the role of the other catecholamine, dopamine, has been less studied. Since dopamine is a potent endogenous inhibitor of angiogenesis and as angiogenesis is essential for ischemic healing, we therefore studied the role played by dopamine during ischemic healing using dopamine D 2 receptor knockout (KOD2) mice. Although concentration of dopamine and its rate-limiting enzyme, tyrosine hydroxylase, was considerably high in the muscle tissues of wild-type and KOD2 mice with unilateral hind limb ischemia (HLI), recovery was significantly faster in the KOD2 mice compared to the wild-type controls, thereby indicating that peripheral dopamine might have a role in this healing process. In addition, we observed significant differences in post-ischemic angiogenesis between these two groups. Our study further revealed that elevated dopamine independently suppressed activation of local tissue-based renin-angiotensin system (RAS), a critical growth factor system stimulating angiogenesis in ischemia. Angiotensin II (ATII) and its receptor, angiotensin receptor type 1 (AT1R), are the key players in RAS-mediated angiogenesis. Dopamine acting through its D 2 receptors in endothelial cells inhibited ATII-mediated angiogenesis by suppressing the expression of AT1R in these cells. This study thus for the first time demonstrates the role played by dopamine in prolonging post-ischemic recovery. Therefore, pharmacological intervention inhibiting the action of dopamine holds promise as future therapeutic strategy for the treatment of HLI and other peripheral arterial diseases.

Prevalence of diabetes, hypertension, and ischemic heart disease in former elite athletes.

PubMed

Kujala, U M; Kaprio, J; Taimela, S; Sarna, S

1994-10-01

Diabetes, hypertension, and ischemic heart disease are less frequent among physically active subjects. The aim of the present national population-based study was to compare the prevalence of these three diseases between former Finnish elite athletes and referents. The subjects consisted of surviving former male athletes who represented Finland between the years 1920 and 1965 at least once in international competitions and referents who at the age of 20 were classified as completely healthy at a medical examination, and who responded to a questionnaire in 1985 (athletes, n = 1,282; referents n = 777). In 1985, they completed a questionnaire with medical, life-style, and psychosocial items; at that time, the leisure physical activity was greater in previous athletes than in referents. The presence or absence of the three diseases was identified from the questionnaire or from at least one of three registers: Finnish hospital inpatient discharge register, reimbursable medication register, and disability pension register. When compared with referents, both endurance and mixed-sports athletes had lower age-adjusted odds ratios (ORs) for all studied diseases. Compared with referents, power-sports athletes had a higher risk for high body mass index (BMI) but a lower risk for ischemic heart disease. Subjects with high BMI had an increased risk for all three diseases. Smokers had a higher risk for diabetes and ischemic heart disease compared with those who were never smokers. After adjustments for age, BMI, smoking history, and occupational group, compared with referents, former endurance athletes had the lowest ORs for diabetes (OR 0.24; 95% confidence interval, 0.07 to 0.81) and ischemic heart disease (OR 0.33; 0.18 to 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon.

PubMed

Gaita, Fiorenzo; Leclercq, Jean François; Schumacher, Burghard; Scaglione, Marco; Toso, Elisabetta; Halimi, Franck; Schade, Anja; Froehner, Steffen; Ziegler, Volker; Sergi, Domenico; Cesarani, Federico; Blandino, Alessandro

2011-09-01

Silent cerebral ischemic lesions have recently emerged as the most frequent complications after pulmonary vein isolation (PVI). To reduce thromboembolic complications, new types of catheters and energy source have been introduced in clinical practice. The study purpose is to compare the incidence of new silent cerebral ischemic events in patients with paroxysmal atrial fibrillation (PAF) undergoing PVI with different ablation technologies. One hundred and eight patients (67% men; age 56 ± 9 years) with PAF were enrolled in a consecutive manner to undergo PVI performed with irrigated radiofrequency (RF) catheter (Group 1, 36 patients), multielectrode catheter (PVAC) associated with duty-cycled RF generator (Group 2, 36 patients) and cryoballoon (Group 3, 36 patients). The protocol included a cerebral magnetic resonance imaging before and after the procedure. After PVI, the following patients showed new silent cerebral ischemic lesions at postprocedural cerebral MRI: 3 patients in Group 1 (8.3%), 14 patients in Group 2 (38.9%), 2 patients in Group 3 (5.6%). PVAC related to higher incidence of silent cerebral ischemic events compared to irrigated RF (P = 0.002) and cryoballoon (P = 0.001), whereas no statistical differences were found between irrigated RF catheter and cryoballoon groups (8.3% vs 5.6%, P = 0.5). At the multivariate analysis, the only independent predictor of new ischemic asymptomatic cerebral lesions after PVI was ablation performed with PVAC (OR 1.48 95% CI 1.19-1.62, P < 0.001). The incidence of silent cerebral lesions after PVI is different depending on technologies used: PVAC increases the risk of 1.48 times compared to irrigated RF and cryoballoon ablation.  © 2011 Wiley Periodicals, Inc.

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy.

PubMed

Austein, Friederike; Riedel, Christian; Kerby, Tina; Meyne, Johannes; Binder, Andreas; Lindner, Thomas; Huhndorf, Monika; Wodarg, Fritz; Jansen, Olav

2016-09-01

Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software. © 2016 American Heart Association, Inc.

Intrinsic A(1) adenosine receptor activation during ischemia or reperfusion improves recovery in mouse hearts.

PubMed

Peart, J; Headrick, J P

2000-11-01

We assessed the role of A(1) adenosine receptor (A(1)AR) activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to 20 min of total ischemia and 30 min of reperfusion. In control hearts, the rate-pressure product (RPP) and first derivative of pressure development over time (+dP/dt) recovered to 57 +/- 3 and 58 +/- 3% of preischemia, respectively. Diastolic pressure remained elevated at 20 +/- 2 mmHg (compared with 3 +/- 1 mmHg preischemia). Interstitial adenosine, assessed by microdialysis, rose from approximately 0.3 to 1.9 microM during ischemia compared with approximately 15 microM in rat heart. Nonetheless, these levels will near maximally activate A(1)ARs on the basis of effects of exogenous adenosine and 2-chloroadenosine. Neither A(1)AR blockade with 200 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) during the ischemic period alone nor A(1)AR activation with 50 nM N(6)-cyclopentyladenosine altered rapidity or extent of ischemic contracture. However, ischemic DPCPX treatment significantly depressed postischemic recovery of RPP and +dP/dt (44 +/- 3 and 40 +/- 4% of preischemia, respectively). DPCPX treatment during the reperfusion period alone also reduced recovery of RPP and +dP/dt (to 44 +/- 2 and 47 +/- 2% of preischemia, respectively). These data indicate that 1) interstitial adenosine is lower in mouse versus rat myocardium during ischemia, 2) A(1)AR activation by endogenous adenosine or exogenous agonists does not modify ischemic contracture in murine myocardium, 3) A(1)AR activation by endogenous adenosine during ischemia attenuates postischemic stunning, and 4) A(1)AR activation by endogenous adenosine during the reperfusion period also improves postischemic contractile recovery.

Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke.

PubMed

Zhong, Chongke; Yang, Jingyuan; Xu, Tan; Xu, Tian; Peng, Yanbo; Wang, Aili; Wang, Jinchao; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Zhang, Yonghong; He, Jiang

2017-08-22

To examine the association between serum matrix metalloproteinases-9 (MMP-9) levels and prognosis of acute ischemic stroke. We measured serum MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular disease were collected at 3 months after stroke onset. During 3 months of follow-up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus. For example, 1-SD (0.32 ng/mL) higher log-MMP-9 was associated with an odds ratio (95% confidence interval) of 1.16 (1.06-1.28) for the combined outcome of death and major disability, 1.12 (1.01-1.23) for major disability, and 1.29 (1.01-1.66) for death. The addition of serum MMP-9 to conventional risk factors improved risk prediction of the combined outcome of death or major disability (net reclassification index 9.1%, p = 0.033; integrated discrimination improvement 0.4%, p = 0.004). Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke. © 2017 American Academy of Neurology.

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Ziai, Wendy; Pokov, Alex N; Bhatt, Deepak L; Alberts, Mark J; Hanley, Dan F

2005-10-01

Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial. Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization. There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02). Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.

Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke.

PubMed

He, Fan; Xia, Cheng; Zhang, Jing-Hua; Li, Xiao-Qiu; Zhou, Zhong-He; Li, Feng-Peng; Li, Wei; Lv, Yan; Chen, Hui-Sheng

2015-01-01

Recent studies have suggested that combination antiplatelet therapy may be superior to monotherapy in the treatment of acute stroke. However, additional prospective studies are needed to confirm this finding. The present trial compared the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in the treatment of non-cardioembolic ischemic stroke within 72 hours of onset. Six hundred and ninety patients aged ⩾ 40 years with minor stroke or transient ischemic attack (TIA) were identified for enrollment. Experienced physicians determined baseline National Institutes of Health Stroke Scale scores at the time of admission. All patients were randomly allocated (1:1) to receive aspirin alone (300 mg/day) or clopidogrel (300 mg for the first day, 75 mg/day thereafter) plus aspirin (100mg/day). The main endpoints were neurological deterioration, recurrent stroke, and development of stroke in patients with TIA within 14 days of admission. After 43 patients were excluded, 321 patients in the dual therapy group and 326 patients in the monotherapy group completed the treatment. Baseline characteristics were similar between groups. During the 2 week period, stroke deterioration occurred in nine patients in the dual therapy group and 19 patients in the monotherapy group. Stroke occurred after TIA in one patient in the dual therapy group and three patients in the monotherapy group. Similar numbers of adverse events occurred in both groups. This study showed that early dual antiplatelet treatment reduced early neurological deterioration in patients with acute ischemic stroke, compared with antiplatelet monotherapy. These results imply that dual antiplatelet therapy is superior to monotherapy in the early treatment of acute ischemic stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.

Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams

PubMed Central

2014-01-01

Background The European Society of Cardiology recommends that patients with >10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects. Methods Twenty-five myocardial perfusion single photon emission computed tomography (SPECT) patients who were regarded as ischemic according to the final report were included. Eleven physicians in nuclear medicine delineated the extent of the ischemic defects. After at least two weeks, they delineated the defects again, and were this time provided a suggestion of the defect delineation by EXINI HeartTM (EXINI). Summed difference scores and ischemic extent values were obtained from four software programs. Results The median extent values obtained from the 11 physicians varied between 8% and 34%, and between 9% and 16% for the software programs. For all 25 patients, mean extent obtained from EXINI was 17.0% (± standard deviation (SD) 14.6%). Mean extent for physicians was 22.6% (± 15.6%) for the first delineation and 19.1% (± 14.9%) for the evaluation where they were provided computerized suggestion. Intra-class correlation (ICC) increased from 0.56 (95% confidence interval (CI) 0.41-0.72) to 0.81 (95% CI 0.71-0.90) between the first and the second delineation, and SD between physicians were 7.8 (first) and 5.9 (second delineation). Conclusions There was large variability in the estimated ischemic defect size obtained both from different physicians and from different software packages. When the physicians were provided with a suggested delineation, the inter-observer variability decreased significantly. PMID:24479846

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

PubMed

Carpenter, Randall S; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin M; Ardelt, Agnieszka A

2016-05-15

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Measuring Quality Improvement in Acute Ischemic Stroke Care: Interrupted Time Series Analysis of Door-to-Needle Time.

PubMed

van Dishoeck, Anne Margreet; Dippel, Diederik W J; Dirks, Maaike; Looman, Caspar W N; Mackenbach, Johan P; Steyerberg, Ewout W

2014-01-01

In patients with acute ischemic stroke, early treatment with recombinant tissue plasminogen activator (rtPA) improves functional outcome by effectively reducing disability and dependency. Timely thrombolysis, within 1 h, is a vital aspect of acute stroke treatment, and is reflected in the widely used performance indicator 'door-to-needle time' (DNT). DNT measures the time from the moment the patient enters the emergency department until he/she receives intravenous rtPA. The purpose of the study was to measure quality improvement from the first implementation of thrombolysis in stroke patients in a university hospital in the Netherlands. We further aimed to identify specific interventions that affect DNT. We included all patients with acute ischemic stroke consecutively admitted to a large university hospital in the Netherlands between January 2006 and December 2012, and focused on those treated with thrombolytic therapy on admission. Data were collected routinely for research purposes and internal quality measurement (the Erasmus Stroke Study). We used a retrospective interrupted time series design to study the trend in DNT, analyzed by means of segmented regression. Between January 2006 and December 2012, 1,703 patients with ischemic stroke were admitted and 262 (17%) were treated with rtPA. Patients treated with thrombolysis were on average 63 years old at the time of the stroke and 52% were male. Mean age (p = 0.58) and sex distribution (p = 0.98) did not change over the years. The proportion treated with thrombolysis increased from 5% in 2006 to 22% in 2012. In 2006, none of the patients were treated within 1 h. In 2012, this had increased to 81%. In a logistic regression analysis, this trend was significant (OR 1.6 per year, CI 1.4-1.8). The median DNT was reduced from 75 min in 2006 to 45 min in 2012 (p < 0.001 in a linear regression model). In this period, a 12% annual decrease in DNT was achieved (CI from 16 to 8%). We could not find a significant association between any specific intervention and the trend in DNT. The DNT steadily improved from the first implementation of thrombolysis. Specific explanations for this improvement require further study, and may relate to the combined impact of a series of structural and logistic interventions. Our results support the use of performance measures for internal communication. Median DNT should be used on a monthly or quarterly basis to inform all professionals treating stroke patient of their achievements.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

PubMed

Fransen, Puck S S; Berkhemer, Olvert A; Lingsma, Hester F; Beumer, Debbie; van den Berg, Lucie A; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama À Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van den Berg, J S Peter; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van Oostenbrugge, Robert J; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

2016-02-01

Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. trialregister.nl Identifier: NTR1804.

Thermal, cardiac and adrenergic responses to repeated local cooling.

PubMed

Janský, L; Matousková, E; Vávra, V; Vybíral, S; Janský, P; Jandová, D; Knízková, I; Kunc, P

2006-01-01

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.

Efficacy and adverse events of cold vs hot polypectomy: A meta-analysis.

PubMed

Fujiya, Mikihiro; Sato, Hiroki; Ueno, Nobuhiro; Sakatani, Aki; Tanaka, Kazuyuki; Dokoshi, Tatsuya; Fujibayashi, Shugo; Nomura, Yoshiki; Kashima, Shin; Gotoh, Takuma; Sasajima, Junpei; Moriichi, Kentaro; Watari, Jiro; Kohgo, Yutaka

2016-06-21

To compare previously reported randomized controlled studies (RCTs) of cold and hot polypectomy, we systematically reviewed and clarify the utility of cold polypectomy over hot with respect to efficacy and adverse events. A meta-analysis was conducted to evaluate the predominance of cold and hot polypectomy for removing colon polyps. Published articles and abstracts from worldwide conferences were searched using the keywords "cold polypectomy". RCTs that compared either or both the effects or adverse events of cold polypectomy with those of hot polypectomy were collected. The patients' demographics, endoscopic procedures, No. of examined lesions, lesion size, macroscopic and histologic findings, rates of incomplete resection, bleeding amount, perforation, and length of procedure were extracted from each study. A forest plot analysis was used to verify the relative strength of the effects and adverse events of each procedure. A funnel plot was generated to assess the possibility of publication bias. Ultimately, six RCTs were selected. No significant differences were noted in the average lesion size (less than 10 mm) between the cold and hot polypectomy groups in each study. Further, the rates of complete resection and adverse events, including delayed bleeding, did not differ markedly between cold and hot polypectomy. The average procedural time in the cold polypectomy group was significantly shorter than in the hot polypectomy group. Cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy.

Thermal responses from repeated exposures to severe cold with intermittent warmer temperatures.

PubMed

Ozaki, H; Enomoto-Koshimizu, H; Tochihara, Y; Nakamura, K

1998-09-01

This study was conducted to evaluate physiological reaction and manual performance during exposure to warm (30 degrees C) and cool (10 degrees C) environments after exposure to very low temperatures (-25 degrees C). Furthermore, this experiment was conducted to study whether it is desirable to remove cold-protective jackets in warmer rooms after severe cold exposure. Eight male students remained in an extremely cold room for 20 min, after which they transferred into either the warm room or the cool room for 20 min. This pattern was repeated three times, and the total cold exposure time was 60 min. In the warm and cool rooms, the subjects either removed their cold-protective jackets (Condition A), or wore them continuously (Condition B). Rectal temperature, skin temperatures, manual performance, blood pressure, thermal, comfort and pain sensations were measured during the experiment. The effects of severe cold on almost all measurements in the cool (10 degrees C) environment were greater than those in the warm (30 degrees C) environment under both clothing conditions. The effects of severe cold on all measurements under Condition A except rectal temperature and toe skin temperature were significantly greater than those under Condition B in the cool environment but, not at all differences between Condition A and Condition B in the warm environments were significant. It was recognized that to remove cold-protective jackets in the cool room (10 degrees C) after severe cold exposure promoted the effects of severe cold. When rewarming in the warm resting room (30 degrees C), the physiological and psychological responses and manual performance were not influenced by the presence or absence of cold-protective clothing. These results suggest that it is necessary for workers to make sure to rewarm in the warm room outside of the cold storage and continue to wear cold-protective clothing in the cool room.

Cardiovascular response to thermoregulatory challenges

PubMed Central

Liu, Cuiqing; Yavar, Zubin

2015-01-01

A growing number of extreme climate events are occurring in the setting of ongoing climate change, with an increase in both the intensity and frequency. It has been shown that ambient temperature challenges have a direct and highly varied impact on cardiovascular health. With a rapidly growing amount of literature on this issue, we aim to review the recent publications regarding the impact of cold and heat on human populations with regard to cardiovascular disease (CVD) mortality/morbidity while also examining lag effects, vulnerable subgroups, and relevant mechanisms. Although the relative risk of morbidity/mortality associated with extreme temperature varied greatly across different studies, both cold and hot temperatures were associated with a positive mean excess of cardiovascular deaths or hospital admissions. Cause-specific study of CVD morbidity/mortality indicated that the sensitivity to temperature was disease-specific, with different patterns for acute and chronic ischemic heart disease. Vulnerability to temperature-related mortality was associated with some characteristics of the populations, including sex, age, location, socioeconomic condition, and comorbidities such as cardiac diseases, kidney diseases, diabetes, and hypertension. Temperature-induced damage is thought to be related to enhanced sympathetic reactivity followed by activation of the sympathetic nervous system, renin-angiotensin system, as well as dehydration and a systemic inflammatory response. Future research should focus on multidisciplinary adaptation strategies that incorporate epidemiology, climatology, indoor/building environments, energy usage, labor legislative perfection, and human thermal comfort models. Studies on the underlying mechanism by which temperature challenge induces pathophysiological response and CVD await profound and lasting investigation. PMID:26432837

Combined effects of family history of CVD and heart rate on ischemic stroke incidence among Inner Mongolians in China.

PubMed

Zhou, Yipeng; Tian, Yunfan; Zhong, Chongke; Batu, Buren; Xu, Tian; Li, Hongmei; Zhang, Mingzhi; Wang, Aili; Zhang, Yonghong

2016-05-01

This study aimed to evaluate the combined effects of family history of cardiovascular diseases (FHCVD) and heart rate on ischemic stroke incidence among Inner Mongolians in China. A prospective cohort study was conducted among 2589 participants aged 20 years and older from Inner Mongolia, China. The participants were divided into four groups according to status of FHCVD and heart rate and followed up from June 2002 to July 2012. Cox proportional hazards models were used to evaluate the combined effects of FHCVD and heart rate on the incidence of ischemic stroke. A total of 76 ischemic stroke occurred during the follow-up period. The observed ischemic stroke cases tended to be older and male, and had higher prevalence of smoking, drinking, hypertension and FHCVD as well as higher systolic and diastolic blood pressures at baseline compared with those who did not experience ischemic stroke. Age- and gender-adjusted hazard ratio (95% confidence interval) of ischemic stroke in the participants with both FHCVD and heart rate ≥ 80 were 2.89 (1.51-5.53), compared with those without FHCVD and heart rate < 80. After multiple adjustment, the association between ischemic stroke risk and both FHCVD and heart rate ≥ 80 remained statistically significant (hazard ratio, 2.47; 95% confidence interval: 1.22-5.01). Our main finding that participants with both FHCVD and faster heart rate have the highest risk of ischemic stroke suggests that faster heart rate may increase the risk of ischemic stroke among people with FHCVD.

The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

PubMed

Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

2010-09-10

5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: rationale and design

PubMed Central

Johnston, S. Claiborne; Easton, J. Donald; Farrant, Mary; Barsan, William; Battenhouse, Holly; Conwit, Robin; Dillon, Catherine; Elm, Jordan; Lindblad, Anne; Morgenstern, Lewis; Poisson, Sharon N.; Palesch, Yuko

2015-01-01

Background Ischemic stroke and other vascular outcomes occur in 10–20% of patients in the 3 months following a TIA or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 hours after TIA or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared to aspirin alone. Design POINT is a prospective, randomized, double-blind, multicenter trial in patients with TIA or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50–325 mg/day, with a dose of 162 mg daily for 5 days followed by 81 mg daily strongly recommended. Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death, by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. Discussion Aspirin is the most common antithrombotic given to patients with a stroke or TIA as it reduces the risk subsequent of stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone. PMID:23879752

Attenuating Ischemic Disruption of K+ Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.

PubMed

Chao, Dongman; Wang, Qinyu; Balboni, Gianfranco; Ding, Guanghong; Xia, Ying

2016-12-01

Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K + homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K + homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K + homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K + homeostasis in the neonatal cortex. Since maintaining cellular K + homeostasis and inhibiting excessive K + fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K + homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonarteritic anterior ischemic optic neuropathy associated with interferon and ribavirin in a patient with hepatitis C.

PubMed

Sharif, Walid; Sheikh, Khayam; De Silva, Ian; Elsherbiny, Samer

2017-04-01

To report a case of a temporal artery biopsy negative anterior ischemic optic neuropathy associated with a recently completed course of pegylated interferon 2 α with ribavirin for chronic hepatitis C. Despite the early presentation with symptoms and prompt treatment with systemic intravenous steroids the patient experienced deterioration of their optic neuropathy over the following few days. Although nonarteritic anterior ischemic optic neuropathy is a common disorder with known risk factors, the timing of onset of symptoms in our patient was suggestive of a possible etiology related to treatment with ribavirin and interferon 2 α, as found in the previously reported cases. There have been a few reported cases of the association between the use of interferon/ribavirin for treatment of chronic hepatitis with nonarteritic anterior ischemic optic neuropathy. In these cases stopping the drug caused some improvement of symptoms or halting the progression of optic neuropathy. Having reviewed the literature on previous cases, we postulate that there may be a dose related reaction to explain the delay and deterioration of vision in some cases despite stopping the drugs. We also advise that any person who is started on this treatment for chronic hepatitis are appropriately counselled as to the potential optic nerve side effect of the drug, based on the evidence reported in the literature.

Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model.

PubMed

Liu, Feng-Di; Zhao, Rong; Feng, Xiao-Yan; Shi, Yan-Hui; Wu, Yi-Lan; Shen, Xiao-Lei; Li, Ge-Fei; Liu, Yi-Sheng; Zhao, Ying; He, Xin-Wei; Yin, Jia-Wen; Zhuang, Mei-Ting; Zhao, Bing-Qiao; Liu, Jian-Ren

2018-05-09

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

Bi-directionally protective communication between neurons and astrocytes under ischemia.

PubMed

Wu, Xiao-Mei; Qian, Christopher; Zhou, Yu-Fu; Yan, Yick-Chun; Luo, Qian-Qian; Yung, Wing-Ho; Zhang, Fa-Li; Jiang, Li-Rong; Qian, Zhong Ming; Ke, Ya

2017-10-01

The extensive existing knowledge on bi-directional communication between astrocytes and neurons led us to hypothesize that not only ischemia-preconditioned (IP) astrocytes can protect neurons but also IP neurons protect astrocytes from lethal ischemic injury. Here, we demonstrated for the first time that neurons have a significant role in protecting astrocytes from ischemic injury. The cultured medium from IP neurons (IPcNCM) induced a remarkable reduction in LDH and an increase in cell viability in ischemic astrocytes in vitro. Selective neuronal loss by kainic acid injection induced a significant increase in apoptotic astrocyte numbers in the brain of ischemic rats in vivo. Furthermore, TUNEL analysis, DNA ladder assay, and the measurements of ROS, GSH, pro- and anti-apoptotic factors, anti-oxidant enzymes and signal molecules in vitro and/or in vivo demonstrated that IP neurons protect astrocytes by an EPO-mediated inhibition of pro-apoptotic signals, activation of anti-apoptotic proteins via the P13K/ERK/STAT5 pathways and activation of anti-oxidant proteins via up-regulation of anti-oxidant enzymes. We demonstrated the existence of astro-protection by IP neurons under ischemia and proposed that the bi-directionally protective communications between cells might be a common activity in the brain or peripheral organs under most if not all pathological conditions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

PubMed Central

2010-01-01

Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

PubMed

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2010-10-19

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

Combined Endovascular Treatment with Distal Radial Artery Coil Embolization and Angioplasty in Steal Syndrome Associated with Forearm Dialysis Fistula.

PubMed

Tercan, Fahri; Koçyiğit, Ali; Güney, Bünyamin

2016-09-01

The present study was performed to define the results of the endovascular treatment with angioplasty and distal radial artery embolization in ischemic steal syndrome associated with forearm arteriovenous accesses. The cases referred to our interventional radiology unit with symptoms and physical examination findings suggestive of ischemic steal syndrome were retrospectively evaluated first by Doppler ultrasonography, and then by angiography. Cases with proximal artery stenosis were applied angioplasty, and those with steal syndrome underwent coil embolization to distal radial artery. Of 589 patients who underwent endovascular intervention for dialysis arteriovenous fistulae (AVF)-associated problems, 6 (1.01 %) (5 female, 1 males; mean age 62 (range 41-78) with forearm fistula underwent combined endovascular treatment for steal syndrome. In addition to steal phenomenon, there were stenosis and/or occlusion in proximal radial and/or ulnar artery in 6 patients concurrently. Embolization of distal radial artery and angioplasty to proximal arterial stenoses were performed in all patients. Ischemic symptoms were eliminated in all patients and the AVF were in use at the time of study. In one patient, ischemic symptoms recurring 6 months later were alleviated by repeat angioplasty of ulnar artery. In palmar arch steal syndrome affecting forearm fistulae, combined distal radial embolization and angioplasty is also an effective treatment method in the presence of proximal radial and ulnar arterial stenoses and occlusions.

Essential role for zinc-triggered p75NTR activation in preconditioning neuroprotection.

PubMed

Lee, Jin-Yeon; Kim, Yu-Jin; Kim, Tae-Youn; Koh, Jae-Young; Kim, Yang-Hee

2008-10-22

Ischemic preconditioning (PC) of the brain is a phenomenon by which mild ischemic insults render neurons resistant to subsequent strong insults. Key steps in ischemic PC of the brain include caspase-3 activation and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, but upstream events have not been clearly elucidated. We have tested whether endogenous zinc is required for ischemic PC of the brain in rats. Mild, transient zinc accumulation was observed in certain neurons after ischemic PC. Moreover, intraventricular administration of CaEDTA during ischemic PC abrogated both zinc accumulation and the protective effect against subsequent full ischemia. To elucidate the mechanism of the zinc-triggered PC (Zn PC) effect, cortical cultures were exposed to sublethal levels of zinc, and 18 h later to lethal levels of zinc or NMDA. Zn PC exhibited the characteristic features of ischemic PC, including caspase-3 activation, PARP-1 cleavage, and HSP70 induction, all of which are crucial for subsequent neuroprotection against NMDA or zinc toxicity. HSP70 induction was necessary for protection, as it halted caspase-3 activation before apoptosis. Interestingly, in both Zn PC in vitro and ischemic PC in vivo, p75(NTR) was necessary for neuroprotection. These results suggest that caspase-3 activation during ischemic PC, a necessary event for subsequent neuroprotection, may result from mild zinc accumulation and the consequent p75(NTR) activation in neurons.

Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

PubMed

von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

2013-01-01

Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p < 0.001). Atrial fibrillation, previous myocardial infarction and previous stroke were significantly more frequent in stroke patients; no differences in other baseline characteristics were found. Minor events are the most common in ischemic cerebrovascular disease, and may constitute a larger proportion than previously reported. TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

Risk factors in various subtypes of ischemic stroke according to TOAST criteria.

PubMed

Aquil, Nadia; Begum, Imtiaz; Ahmed, Arshia; Vohra, Ejaz Ahmed; Soomro, Bashir Ahmed

2011-05-01

To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Cross-sectional, observational study. Ziauddin Hospital, Karachi, from January to December 2007. Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p < 0.05. Out of the 100 patients with acute ischemic stroke, mean age at presentation was 63.5 years. Risk factor distribution was hypertension in 85%, Diabetes mellitus in 49%, ischemic heart disease in 30%, dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke.