Recombinant tissue-plasminogen activator rt-PA

The severity of the neurological deficit at the time of stroke onset is a major predictor of stroke outcome. In an analysis of the placebo-treated patients in the National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue-plasminogen activator (rt-PA) study, the best acute predictor of a poor outcome at 1 year was an National Institute of Health Stroke Scale (NIHSS) score >17 for patients over 70 years. These criteria had a high specificity (98%), but sensitivity was only 31%. The low sensitivity of the acute NIHSS score alone in predicting... 

Also known as recombinant tissue Plasminogen Activator (rt-PA). It is produced by recombinant DNA technology from human tissue culture. It specifically activates plasminogen bound to the fibrin clot. This minimises the risk of systemic bleeding. 

During the time that UK was unavailable, increased experience and familiarity were gained with other agents, such as recombinant tissue plasminogen activator (rt-PA) and reteplase. 

For hypothermia, one major possible difficulty involves the effect of low temperature on metabolism and enzyme activity. Many pharmaceutical agents have reduced biological activity at lower temperature compared with higher temperature. The thrombolytic activity of recombinant tissue plasminogen activator (rt-PA), for example, is clearly temperature dependent, with decreased activity at lower temperature (1). Thus, the assumption that hypothermia will not have an adverse effect on other treatment agents cannot be presumed. Hypothermia is also known to reduce the activity of inflammatory and antiinfectious biological processes. This could potentially result in increased susceptibility to infection. This possibility is of particular concern because infections are a major cause of morbidity in stroke patients (2). Therefore, combination therapy with hypothermia and antiinflammatory agents could potentially worsen outcome. 

Alteplase is a recombinant tissue plasminogen activator (rt-PA). As a result of its production in eukaryotic Chinese hamster ovary (CHO) cells, carbohydrate residues are present as in the native substance. At the therapeutically used dosage, alteplase loses its fibrin dependence and thus also activates circulating plasminogen. In fresh myocardial infarctions, alteplase appears to produce better results than does streptokinase. 

As discussed in Chapter 3, proteins and mABs distribute initially into the plasma volume and then more slowly into the interstitial fluid space. It can be seen from Table 32.11 that the initial distribution volume of interleukin-2 (IL-2) IL-12/ granulocyte colony-stimulating factor (G-CSF)/ and recombinant tissue plasminogen activator (rt-PA) approximates that of plasma volume. In contrast/ the initial distribution volume of FIX is approximately twice that of plasma volume. On the other hand/ the volumes of distribution at steady state (Vd(ss)) for IL-12/ G-CSF/ and rt-PA are considerably smaller than is the Vd(ss) of inuliii/ a marker for extracellular fluid space (ECF). When distribution volume estimates are much less than expected values for ECF/ they could reflect the slow transport of large molecules across membranes and the fact that either assay sensitivity or sampling time has been inadequate to characterize the true elimination phase of the compound. 

FIGURE 32.9 Clearance of different forms of recombinant tissue plasminogen activator (rt-PA) in rabbits after administration of rt-PA alone (A) or in combination with p-aminophenyl-a-D-mannoside-bovine serum albumin ( ). (Reproduced with permission from Lucore CL et al. Circulation 1988 77 906-14.)... 

Ma, L., et al., Can baseline magnetic resonance angiography (MRA) status become a foremost factor in selecting optimal acute stroke patients for recombinant tissue plasminogen activator (rt-PA) thrombolysis beyond 3 hours Neurol Res, 2009. 31(4) p. 355-61. 

A new optimism emerged after the advent of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA, Alteplase) as the first FDA-approved... 

In the Plasminogen-activator Angioplasty Compatibility Trial (PACT), 606 patients with STEMI were randomized to placebo or reduced-dose recombinant tissue plasminogen activator (rt-PA) in the... 

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