Total Thiols and MDA Levels in Patients with Acute Myocardial Infarction Before and After Reperfusion Therapy

Background: Reactive oxygen species have been implicated in the pathogenesis of ischemic and reperfusion injury. In the current work we have measured malondialdehyde (MDA), total thiols, total CK, CK-MB and AST in ECG proven acute myocardial infarction (AMI) patients immediately after admission and 24 hours after administration of thrombolytic agent streptokinase, and in healthy controls. Methods: Blood samples from 44 AMI patients and 25 age and sex matched healthy controls were obtained and analyzed for MDA, total thiols using spectrophotometric methods and cardiac enzymes CK, CK-MB and AST using automated analyzer. Results: We have found significant increase in MDA, CPK, CK-MB, AST (p< 0.001) and significant decrease in total thiols (p<0.001) in AMI patients after thrombolytic therapy compared to values at admission, and healthy controls. MDA correlated negatively with total thiols (r = - 0.333, p<0.05) and positively with CK-MB (r = 0.491, p<0.01) in AMI patients after thrombolytic therapy. Conclusions: Reperfusion following thrombolytic therapy increases reactive oxygen species with concomitant decrease in antioxidant total thiols

Spectrophotometric analysis of thrombolytic activity: SATA assay

Introduction: Measurement of thrombolytic activity i.e. clot lysis is crucial for research and development of novel thrombolytics. It is also a key factor in assessment of the effectiveness of conventionally used thrombolytic agents in the clinic, which are the choice effective therapies for myocardial infarction and ischemic stroke. Previous methods used for the assessment of thrombolytic activity are often associated with some drawbacks such as being costly, time-consuming, complication and low accuracy. Here, we introduce a simple, economic, relatively accurate and fast method of spectrophotometric analysis of thrombolytic activity (SATA) assay, standardized by tissue plasminogen activator (tPA), which can quantitatively measure in vitro thrombolytic activity. Methods: Blood clots were formed, uniformly, by mixing citrated whole blood with partial thromboplastin time (PTT) reagent, together with calcium chloride. Then, designated concentrations of tPA were added to the samples, and the released red blood cells from each clot were quantified using spectrophotometry (λmax= 405 nm) as an indicator of thrombolytic activity. The accuracy of the method was tested by assessment of dose-responsibility against R2 value obtained by linear equation and measurement of limit of detection (LOD) and limit of quantification (LOQ). The SATA assay was validated in comparison with some currently used techniques. Results: A linear relationship was obtained between different concentrations of tPA versus the spectrophotometric absorbance of the related dilutions of lysed clots, at λmax = 405 nm. Calculated R2 values were greater than 0.9; with LOD of 0.90 μg/mL of tPA (436.50IU) and LOQ of 2.99 μg/mL of tPA (1450.15IU). Conclusions: Conclusively, the SATA assay is a very simple quantitative method with repeatable and reproducible results for estimating the potency of an unknown thrombolytic agent, and calculating the activity as delicate as 1 μg/mL of tPA (485 IU/mL of thrombolytic dose). © 2018 The Author(s)

Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis

Background: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. Objective: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. Methods: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (Crl)) as a function of the additional time delay associated with angioplasty. \ Results: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean ( SE) angioplasty-related time delay ( over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis ( OR = 0.68 ( 95% Crl 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 ( 95% Crl 0.20 to 0.51); for non-fatal stroke OR = 0.24 ( 95% Crl 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. Conclusions: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1- month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays

Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments

Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II trials

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post–tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of ≥4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P&#60;0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS &#8804;7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P&#60;0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post–tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.&lt;/p&gt

Editor's choice : European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of acute limb ischaemia

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RESCUING THE ISCHEMIC PENUMBRA—OUR EXPIRIENCE

Objectives: Over one million strokes per year are occurring in Europe. Brain stroke is one of the most important death and disability causes in Europe and USA. The main role of perfusion is to determine the border of insult core and ischemic penumbra. Penumbra can be saved with thrombolytic therapy but core have irreversible injuries and represent death of brain cells. Aim: to determine the role of CT brain perfusion in cases of acute brain stroke and following thrombolytic therapy. Methods: We examined 64 patients with acute brain stroke who received thrombolytic therapy after that. All patients were examining on 16 MDCTwith 50 ml of iodine contrast agent following the standard procedure for CT perfusion. Patients were 34 male and 30 female with middle age of 64 years. MRI was made after thrombolytic therapy and compare with perfusion results before therapy. Results: Using an artery and a vein as reference three parameters were measured — blood flow (CBF), blood volume (CBV) and mean transit time (MTT), for each patient. Hemorrhagic was find in 9 (14.01%) patients after thrombolytic therapy. 4 (6.25%) other patients develop new stroke of same but mostly other side of brain. 8 (12.50%) more patients finished lethally. From other 42 patientswith thrombolytic therapywe can positively say that in 31 (48.44%) patients penumbrawas rescued. For other 11 (17.19%) stroke was same size like firstly involved core and penumbra but not bigger. Conclusion: CT perfusion plays major role by showing a curable parts of tissue in brain stroke

Guidelines on fibrinogen assays

No abstract available