Thrombolysis in acute ischaemic stroke
- aDepartment of Clinical Neurology, Ipswich Hospital, Ipswich and Department of Clinical Neurology, Addenbrooke's Hospital, Cambridge, UK, bDepartment of Clinical Neurology, Addenbrooke's Hospital, Cambridge, UK, cDepartment of Stroke Medicine, Box 135, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
- Dr Warburtonliz.warburton{at}msexc.addenbrookes.anglox.nhs.uk
- Received 18 February 2000
- Accepted 4 July 2000
The primary deficit in acute ischaemic stroke is one of impaired blood flow. Part of the cerebral circulation is occluded either by in situ thrombosis, or embolism from the heart or a more proximal artery (for example, the ipsilateral internal carotid artery). Angiographic studies of the cerebral circulation in acute stroke demonstrate occluding thrombus in up to 80% of patients.1 The aim of thrombolytic therapy therefore is to lyse an occluding thrombus or embolus and reduce the volume of cerebral tissue irreversibly damaged. Such an approach is of course successfully employed in the treatment of acute myocardial infarction.2 However a major complication of thrombolysis in stroke is cerebral haemorrhage which could offset any beneficial effects. Here we review the available evidence for thrombolysis in acute stroke and suggest imaging methods that could be used to aid future selection of patients who are most likely to benefit from such treatment.
Experimental rationale for thrombolysis in stroke
Data from animal stroke models confirm that cerebral blood flow can be restored to near normal levels after administration of recombinant tissue plasminogen activator (rtPA)3 and that thrombolysis results in smaller infarcts and improved neurological function.4-6 Comparison of streptokinase with rtPA suggested that, although their effectiveness in producing thrombolysis was comparable, streptokinase was less clot specific and animals treated with it had increased frequency and severity of cerebral haemorrhage.7 Animals treated with rtPA had the same frequency of cerebral haemorrhages as those treated with saline but the proportion of large haematomas was increased.6
In humans, thrombolytic therapy was first tried over 40 years ago but was largely abandoned due to excess mortality from major haemorrhagic complications.8 When computed tomography became widely available interest in the use of thrombolysis returned, leading to several larger randomised controlled trials. A dose escalation study using rtPA reported that …
