PubMed Health⌕ Search

PubMed · 12597608

Stroke--acute interventions.

Abstract

The reduction of blood flow to parts of the brain is the cause of ischemic stroke leading to functional deficits and, if prolonged, to irreversible neurological and morphological defects. The fast reperfusion, therefore is the most important therapeutic strategy and was proven to be effective in clinical trials. Steps to intervene with secondary biochemical, molecular, or inflammatory disturbances were not successful so far. Since direct therapeutic interventions are limited, the general management of the stroke victim is of utmost importance--and was shown to be most successful in dedicated stroke units. Acute therapeutic interventions in ischemic stroke can only be successful as long as tissue in the area of the ischemic compromise is still viable. The area of irreversible damage can be identified and distinguished from the penumbral zone, i.e., tissue with impaired function but preserved morphology by functional imaging modalities, like positron emission tomography (PET) or perfusion-(PW) and diffusion-weighted (DW) magnetic resonance imaging (MRI). In such studies it was demonstrated that a large portion of the final infarct is irreversibly affected in the first few hours in many patients. A considerable tissue volume is viable but critically hypoperfused; a smaller portion of the final infarct is sufficiently perfused and in this area secondary and delayed biochemical and molecular mechanisms contribute to the damage. Based on this concept the improvement of perfusion within the time window of opportunity must be the primary goal in treatment of ischemic stroke, and neuroprotective and other strategies can only play a supportive and additive role. That this is the case can be seen from the results of many controlled therapeutic trials, in which up to now only thrombolytic therapy with a 3 h time window for systemic and a 6 h time window for intraarterial application proved its efficacy, whereas all trials with neuroprotective, anti-inflammatory or anti-apoptotic strategies failed. Since the direct treatment strategies are limited the acute management of stroke victims is of utmost importance: This can be achieved optimally in dedicated stroke units in which the outcome was significantly improved over the regular care. It is still to be investigated if invasive strategies--e.g., craniectomy and hypothermia--or the combination of reperfusion and neuroprotective therapy can improve the outcome after ischemic stroke.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

W D Heiss. 2002. Stroke--acute interventions.. https://doi.org/10.1007/978-3-7091-6137-1_3

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury.

Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known. Tissue factor (TF) and thrombin, two potent procoagulant and proinflammatory mediators, are recognized to play significant roles in myocardial I/R injury. To investigate the role of TF and thrombin in myocardial I/R injury, we used rabbit and murine in situ coronary artery ligation models. Increased TF mRNA, antigen, and activity were found in ischemic cardiomyocytes. Administration of an inhibitory antirabbit TF monoclonal antibody before or during the onset of ischemia resulted in a significant reduction in infarct size. Functional inhibition of thrombin with hirudin also reduced the infarct size. However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury.

Ancrod↗

Stroke trials: what have we learned?

We reviewed the recent, major, therapeutic trials of intravenous thrombolytic therapy and ancrod for ischemic stroke. Randomized, controlled studies of acute ischemic stroke treatment were reviewed. Several post-FDA approval intravenous tPA studies were reviewed to understand the experience of this medication in practice. STAT trial was the major study using ancrod. Of multiple intravenous thrombolytic studies, the NINDS study of intravenous tPA was the only study to demonstrate a significantly higher percentage of patients with complete recovery or minimal deficit at three months. Studies in communities utilizing intravenous tPA for stroke illustrate the need for close adherence to the NINDS study protocol or else the risk of tPA use may exceed the benefits.

Ancrod↗

Optimal timing of thrombolytic therapy in acute ischaemic stroke.

The clinical benefit of thrombolytic therapy for patients experiencing acute cerebral ischaemia has been demonstrated by both clinical trials and phase IV studies. However, such treatments must be initiated in a rapid manner, with treating physicians adhering to strict protocols designed to minimise delays and maximise safety. The efficacy of intravenous drug administration has been established with alteplase (recombinant tissue plasminogen activator; tPA) and ancrod, but only if these drugs can be administered within 3 hours of symptom onset. The use of alteplase beyond this timeframe, or outside of established protocols, may be hazardous. The use of alternative intravenous thrombolytic agents, such as streptokinase, also appears hazardous. Intra-arterial delivery of thrombolytic drugs such as pro-urokinase may extend clinical benefit to the 6-hour time frame.

Ancrod↗