Experimental studies on thrombin inhibition in acute- and chronic models of vessel wall injury

Background: The number of percutaneous coronary interventions (PCI) performed worldwide has increased dramatically during the last decade. Complication rates have decreased over time, however the restenosis phenomenon remains an unsolved issue. Thrombin is the key regulator in the pro-coagulant state following PCI. As well as its role in coagulation activation, thrombin also promotes proliferation and migration of smooth muscle cells, which is of pivotal importance in the restenosis process. Objective: The aim of the study was to determine if thrombin inhibition, achieved through antithrombin (AT) or the direct, small molecule thrombin inhibitor melagatran, could favourably alter the acute- and long-term response to deep vessel wall injury in porcine coronary arteries.Methods: In three studies on the acute response to vessel wall injury, the effects of locally delivered AT, and locally or systemically delivered melagatran, were investigated. After local delivery by special local drug delivery catheters, the content of AT in the vessel wall was quantified by immunofluorescence technique using a semi-quantitative method, and that of melagatran was analysed by autoradiography. Autologus platelets were labelled with In111 and infused into the pigs. In addition, in the study with systemically infused melagatran, I125 labelled fibrinogen was injected. A balloon injury was induced to the coronary vessel wall. One hour after balloon injury the pigs were sacrificed, the heart explanted and the radio-activity of the injured vessel segments investigated in a gamma well counter. The number of platelets and amount of fibrin was calculated. In two other studies, the effects of locally delivered AT or high concentration, high purity antithrombin fraction (HCHP-AT), on the long-term response, i.e. development of stenosis, after deep coronary artery wall injury, were investigated. Normo-cholesterolemic Swedish landrace pigs were subjected to a deep balloon or stent injury to the coronary vessel walls and then followed for four weeks, whereafter they were sacrificed. In a sixth study using a double-injury model, hypercholesterolemic Yucatan mini-pigs were treated with a long-term infusion of melagatran after balloon injury or implant of stents in the coronary arteries. The animals were followed for four weeks before being sacrificed. In the three latter studies, the hearts were explanted after sacrifice and the injured vessel segments investigated histo-morphologically. The percent area stenosis, lumen and the different vessel wall areas were determined. In the study with HCHP-AT, an additional quantitative coronary angiogram (QCA) was performed.Results: Local delivery of antithrombin after balloon injury in coronary vessels resulted in detectable amounts of AT in the inner part of the vessel wall, and a significant reduction of platelet deposition as compared to control treatment with pure albumin. It was not possible to deposit any melagatran by local delivery and there was no effect on platelet deposition. Systemically administered melagatran, on the other hand, significantly inhibited both platelet and fibrin deposition in an acute model. There was no favourable effect on vascular wall remodelling or neointima proliferation after coronary vascular wall injury by either local delivery of AT or HCHP-AT nor of long term infusion of melagatran.Conclusions: Thrombin inhibition by either local administration of endogenous antithrombin or systematically administered low molecular weight thrombin inhibitor melagatran, inhibited the acute thrombotic response after vascular wall injury in porcine coronary models, but there were no effects on long-term stenosis/restenosis development.Key words: animal model, antithrombin, fibrinogen, histomorphology, melagatran, percutaneous coronary intervention, platelets, restenosis, stent, thrombin inhibition, thrombosis

Valanlys.se: A Graphical Trend Analysis Tool - Visualizing Political Trends From Semantically Analyzed Twitter Posts

The Internet has during a relatively short period of time changed people’s perception on information and its availability. It has never before been so easy to get information about practically anything, just a few clicks away. The problem today is that we are living in a society with an information overflow, it can be really time consuming finding relevant facts in the ocean of data. A young entrepreneurial company, Saplo AB, thought of a solution: let the computers find whats relevant for us and save us both time and effort. They created a highly advanced algorithm that works in a similar fashion to the human brain. With the algorithm computers can now read, understand and sort text. Saplo has so far only focused their services toward other companies but now they want to show the rest of the world that their technique is capable of. This master thesis aims to provide Saplo with a platform for information visualization, a tool to visually present the result of their technology. To narrow down the work, the Swedish election was chosen as the subject for this master thesis. What it tries to answer is: "How to create a real-time feedback system for the political environment with automated trend-analysis?"<br> The master thesis goes through all necessary steps to complete this visualization tool from research to implementation and testing. The project results in a fully functional website that gathers tweets (messages) from Twitter that are related to the Swedish election. All the tweets are sent to Saplo to be analyzed and are there given a trend index. They are then forwarded to the website and presented in real-time. The trend index is used to draw a trend for the political party that the tweet is concerning. The master thesis also discusses possible improvements and interesting ideas for further development.<br><br> Internet har på relativt kort tid förändrat vår syn på information och dess tillgänglighet. Det har aldrig tidigare varit så enkelt att få tag på information om praktiskt taget vad som helst, bara några mus-klick bort. Problemet är snarare att vi i dagens samhälle drunknar i för mycket information, tiden läggs istället på att sortera ut relevant information. Ett ungt entreprenörsmässigt företag, Saplo AB, har kommit på en lösning: låta datorerna hitta vad som är relevant information och spara oss både tid och ansträngning. Saplo skapade en högst komplex algoritm som arbetar på ett liknande sätt som den mänskliga hjärnan. Med denna algoritm kan datorer nu läsa, förstå och sortera text för oss. Saplo har än så länge endast fokuserat sin service mot andra företag men nu ville de ta steget att visa världen vad deras teknik är kapabel till. Examensarbetet försöker tillhandahålla Saplo en plattform för informations visualisering, ett verktyg för att visuellt presentera resultatet av deras teknologi. För att begränsa arbetet till en rimlig nivå, valdes det svenska valet som ämne för detta examens arbetet. Examensarbetet vill besvara frågeställningen: "Hur skapar man ett real-tids feedback system för politiska klimatet med automatiska trendanalyser?".<br> Vi går igenom alla nödvändiga faser i utvecklingen, från undersökning till implementering och testning. Projektet resulterade i en fullt fungerande hemsida som samlar in tweets (meddelanden) ifrån Twitter som är relevanta till det Svenska valet. Alla tweets skickas till Saplo för att bli analyserade och ges där ett trendindex. Därefter skickas de vidare till hemsidan för publicering i realtid. Tweetets tillhörande trendindex används för att rita upp en trend för det parti som tweetet nämnde. Examensarbetet kommer även ta upp en diskussion angående förbättringar och förslag på framtida förändringar

Long-term safety and efficacy of drug-eluting and bare metal stents in saphenous vein grafts

Background Long-term safety and efficacy data of drug-eluting stents (DESs) in saphenous vein grafts (SVGs) are lacking. This study sought to compare the clinical outcomes of DES versus bare metal stents (BMS) in SVGs. Methods We studied all stent implantations in SVGs in Sweden during 74 months between 2005 and 2011 registered in the Swedish Coronary Angiography and Angioplasty Registry. We evaluated outcome in patients who received DES compared with those who received BMS after adjustments for differences in clinical, vessel, and lesion characteristics. Results Mean follow-up time was 3 years and 4 months. A total of 4,576 stents, implanted at 3,063 procedures, were included in the analysis of which 2,499 stents (54.6 %) were BMS and 2,077 (45.4%) were DES. The outcome analysis was based on 190 stent thromboses, 898 restenoses, and 523 deaths. The incidence of stent thrombosis did not differ between groups. When adjusted for baseline characteristics, including a propensity score for receiving DES, the incidence of restenosis was significantly lower with DES as compared with BMS (risk ratio 0.83, 95% CI 0.70-0.97, P = .019). There was a difference in mortality in the crude analysis between DES and BMS, and after multivariable adjustment, this difference remained statistically significant (risk ratio 0.80, CI 0.65-0.99, P = .038). Conclusions The use of DES compared with BMS in SVGs was associated with a significantly lower adjusted incidence of restenosis and death in this large, national, all-encompassing propensity adjusted observational study. (Am Heart J 2012;164:87-93.

Blood lactate is a predictor of short-term mortality in patients with myocardial infarction complicated by heart failure but without cardiogenic shock

Background: Mortality in patients with acute myocardial infarction (AMI) has improved substantially with modern therapy including percutaneous coronary interventions (PCI) but remains high in certain subgroups such as patients presenting with overt cardiogenic shock. However, the risk for AMI in patients presenting acutely with signs of heart failure but without cardiogenic shock is less well described. We aimed to identify risk factors for mortality in AMI patients with heart failure without overt cardiogenic shock. Methods: Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we identified patients with operator-registered heart failure (Killip class II-IV), and evaluated predictors of mortality based on clinical factors from review of patient records. Results: A total of 1260 unique patients with acute myocardial infarction underwent PCI in 2014, of which 77 patients (7%) showed signs of heart failure (Killip II-IV) Overall 30-day mortality in patients with Killip class II-IV was 20% (N = 15). In patients classified Killip IV (1%), 30-day mortality was 50% (N = 6). In patients presenting with mild to moderate heart failure (Killlip class II-III), 30-day mortality was 14% (N = 9). In patients with Killip class II-III, lactate ≥2.5 mmol/L was associated with 30-day mortality, whereas systolic blood pressure < 90 mmHg, age, sex and BMI were not. In patients with lactate < 2.5 mmol/L 30-day mortality was 5% (N = 2) whereas mortality was 28% (N = 7) with lactate ≥2.5 mmol/L. This cut-off provided discriminative information on 30-day mortality (area under ROC curve 0.74). Conclusions: In patients with AMI and signs of mild to moderate heart failure, lactate ≥2.5 mmol/L provides additional prognostic information. Interventions to reduce risk may be targeted to these patients

Successful resuscitation with mechanical CPR, therapeutic hypothermia and coronary intervention during manual CPR after out-of-hospital cardiac arrest

A 62-year-old man suffered out-of-hospital cardiac arrest and was treated with mechanical compression-decompression during transport to the hospital. In the emergency department, 28 min after cardiac arrest, spontaneous circulation returned briefly but the patient rapidly became asystolic and mechanical compression-decompression was again applied. After further resuscitation a spontaneous circulation returned and the patient was transferred, deeply comatose, to the coronary intervention laboratory while therapeutic hypothermia was induced. In the laboratory the heart arrested again and coronary angiography was performed during manual CPR revealing a left main stem occlusion. After successful reperfusion of the heart the patient was transferred to the intensive care unit with an intra-aortic balloon pump. The patient was treated with hypothermia for 24 h and awoke without neurological sequelae after a sustained intensive care period of 13 days. The present case is an example of how modern resuscitation principles implementing new clinical and experimental findings may strengthen the chain of survival during resuscitation

Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Aims Immediate treatment with a loading dose of clopidogrel at diagnosis of ST-segment elevation myocardial infarction (STEMI) is recommended by ESC/AHA/ACC guidelines in patients eligible for primary percutaneous coronary intervention (PCI). However, the evidence for this practice is scarce. Methods and results All patients who underwent PCI for STEMI in Sweden between 2003 and 2008 were identified from the national Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Patients with concomitant warfarin treatment and patients not having received aspirin upstream were excluded, leaving 13 847 patients for the analysis. Groups were compared for death and myocardial infarction (MI) during 1-year of follow-up using Cox regression models with adjustment for differences in baseline characteristics by propensity score methods. The combined primary endpoint of death or MI during 1-year follow-up occurred in 1325 of 9813 patients with upstream clopidogrel and in 364 out of 4034 patients without upstream treatment. After propensity score adjustment, a significant relative risk reduction (HR 0.82, 95% CI 0.73-0.93) in death/MI at 1 year was observed. The secondary endpoint of total 1-year death was significantly reduced (HR 0.76, 95% CI: 0.64-0.90), while the incidence of 1-year MI did not show any significant reduction (HR 0.90, 95% CI 0.77-1.06). Similar results were observed in multivariate analysis on top of propensity scoring and in sensitivity analyses excluding patients without clopidogrel and aspirin at discharge. Conclusion This large observational study suggests that upstream clopidogrel treatment prior to arrival at the catheterization lab is associated with a reduction in the combined risk of death or MI as well as death alone in patients with STEMI treated with primary PCI

Internationell och nationell konsensus om bästa vård efter hävt hjärtstopp. Många patienter blir helt återställda.

An international consensus report on postresuscitation care after cardiac arrest has recently been published. Its content and main messages are in line with the recommendations from The Swedish Resuscitation Council, which include: diagnosing and treating the underlying disease, offering good general intensive care, considering hypothermia treatment, standardising prognostication and follow-up