Thrombolytic Intervention in Acute Thrombotic and Embolic Stroke
'l'he use of'thrombolytic agents in acute cer-e- profile (toxic to therapeutic ratio) and close rebra1 ischernia is experi~nental.Irl this review we will sponse, anti some effect o n neurologic outcome. consider the rationale for- the study of thrombolysis Unknowns that may affect the safety aritl ef'flcac:); in acute cerebral ischemia, pertinent aspects of'the of' the throml~olyticagent include the risk of' exnatur-al history of cerel)rovascular thrornbosis aud tending petcchiae common to ceret~ralernt)olic inemholisrn including the role of hemorrhag,'YIC ti-ans- ~ u r y the , c o ~ i t r i h ~ ~ t i(if o nany) of fibrin-dependent fbrmation, specific thron1l)olytic agents, their use cerebrovascular thrombi to vascular protection in in recent studies in stroke patients, and conlplica- per-i-ischemic zoues, flow limitations in occlutleti tions that may attend their use. A particular focus vasc.ular segments, and the contribution to thrornof' this review will I x the efficacy of thronholytic hosis of' the cerebrovascular enclothclial response agents based o n specific cerebrovascular anatomic to ischemia. considerations. Kecent efforts to evaluate the eff'icacy of thrombus lysis i l l acute stroke rest on the observaNATURAL HISTORY tion that thl-omt)osis, whether- migratory (as in cardiac embolis~no r local artel-y-to-artery embolism) iZthel-othl-ombotic arid embolic occlusive diso r superimposed o n the atherosclerotic process, is ease underlie 80 to 90% of' focal cer-et~ralischcniic the most conimon PI-ecipitant of' occlusive ccrebro- events presenting as strokes within 8 to 24 houi-s vascular disease. of' symptom onset,' and 50 to 70% of all strokes Central to the study of' thrombolysis is the hy- pi.ospectively accurriuhteti iu contenipor-;try stroke pothesis that prompt restoration of' blood f o w is regisrries.',:' Thrombosis and embolism from athessential for- neuronal recovery. T h e principal goal erornas involve the large extracranial (carotid arid of thromholytic therapy for stroke is the timely vertel)ral) vessels ancl distal dependent intracranial lysis of' oc-clucling thronlbus and restoration of'cir- vesscls. Additional causes of focal syrn1)toms not culation with reduction of ischemia in the affected genel-ally associated with major vasculal- obstructerritory, with a nlirlirnum risk of significant intra- tion include sn~all,deep infarcts of' the 1acun;tr cranial and systemic hemorrhage. type' ant1 intracere1)ral hemorrhage. Pharmaceutical thrombolysis in cercbrovascu' l h e complex processes of' thrornbosis ancl atlilar ischernia has entailed the use of urokinase, eroma fijl.matiou are interrelated and have bec.11 streptokinase, plasminogen-activator complexes, reviewed el~ewhere.~' Significant plaque forrnatior~ and, more recently, I-econlbinant tissue plasrnino- leading to progressive luminal stenosis and throrngen activator by either systenlic o r local intra-arte- ljosis in most populations is found in the cervical rial delivery. Clinical investigations with these internal carotid artery flow divider, the carotid siagents have sought to define a n acceptable safety phon, middle cerebral artery ( M C A ) origin, verte-
'l'his reseat-cli \vas supported in part b y gt.ant 1-KO I-NS'L(i$)45(Gll)Z)from the X;itiot~alI ~ ~ s t i t u t e s ol Health, Retliesda, Maryland. Keprit~rrequests: Dr. dcl Zoppo, Dcpartnlerrt of' hlolccuI;~rand E:spcritl~cnt;tlhlcclitit~e.S c ~ i p p s Clinic and Research Foundation, La lolls,
'l'he use of'thrombolytic agents in acute cer-e- profile (toxic to therapeutic ratio) and close rebra1 ischernia is experi~nental.Irl this review we will sponse, anti some effect o n neurologic outcome. consider the rationale for- the study of thrombolysis Unknowns that may affect the safety aritl ef'flcac:); in acute cerebral ischemia, pertinent aspects of'the of' the throml~olyticagent include the risk of' exnatur-al history of cerel)rovascular thrornbosis aud tending petcchiae common to ceret~ralernt)olic inemholisrn including the role of hemorrhag,'YIC ti-ans- ~ u r y the , c o ~ i t r i h ~ ~ t i(if o nany) of fibrin-dependent fbrmation, specific thron1l)olytic agents, their use cerebrovascular thrombi to vascular protection in in recent studies in stroke patients, and conlplica- per-i-ischemic zoues, flow limitations in occlutleti tions that may attend their use. A particular focus vasc.ular segments, and the contribution to thrornof' this review will I x the efficacy of thronholytic hosis of' the cerebrovascular enclothclial response agents based o n specific cerebrovascular anatomic to ischemia. considerations. Kecent efforts to evaluate the eff'icacy of thrombus lysis i l l acute stroke rest on the observaNATURAL HISTORY tion that thl-omt)osis, whether- migratory (as in cardiac embolis~no r local artel-y-to-artery embolism) iZthel-othl-ombotic arid embolic occlusive diso r superimposed o n the atherosclerotic process, is ease underlie 80 to 90% of' focal cer-et~ralischcniic the most conimon PI-ecipitant of' occlusive ccrebro- events presenting as strokes within 8 to 24 houi-s vascular disease. of' symptom onset,' and 50 to 70% of all strokes Central to the study of' thrombolysis is the hy- pi.ospectively accurriuhteti iu contenipor-;try stroke pothesis that prompt restoration of' blood f o w is regisrries.',:' Thrombosis and embolism from athessential for- neuronal recovery. T h e principal goal erornas involve the large extracranial (carotid arid of thromholytic therapy for stroke is the timely vertel)ral) vessels ancl distal dependent intracranial lysis of' oc-clucling thronlbus and restoration of'cir- vesscls. Additional causes of focal syrn1)toms not culation with reduction of ischemia in the affected genel-ally associated with major vasculal- obstructerritory, with a nlirlirnum risk of significant intra- tion include sn~all,deep infarcts of' the 1acun;tr cranial and systemic hemorrhage. type' ant1 intracere1)ral hemorrhage. Pharmaceutical thrombolysis in cercbrovascu' l h e complex processes of' thrornbosis ancl atlilar ischernia has entailed the use of urokinase, eroma fijl.matiou are interrelated and have bec.11 streptokinase, plasminogen-activator complexes, reviewed el~ewhere.~' Significant plaque forrnatior~ and, more recently, I-econlbinant tissue plasrnino- leading to progressive luminal stenosis and throrngen activator by either systenlic o r local intra-arte- ljosis in most populations is found in the cervical rial delivery. Clinical investigations with these internal carotid artery flow divider, the carotid siagents have sought to define a n acceptable safety phon, middle cerebral artery ( M C A ) origin, verte-
'l'his reseat-cli \vas supported in part b y gt.ant 1-KO I-NS'L(i$)45(Gll)Z)from the X;itiot~alI ~ ~ s t i t u t e s ol Health, Retliesda, Maryland. Keprit~rrequests: Dr. dcl Zoppo, Dcpartnlerrt of' hlolccuI;~rand E:spcritl~cnt;tlhlcclitit~e.S c ~ i p p s Clinic and Research Foundation, La lolls,
