| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2007;38:961.)
© 2007 American Heart Association, Inc.
Original Contributions |
From the Neurosonology and Stroke Research Program (G.T., V.K.S., A.Y.L., A.V.A.), Barrow Neurological Institute, Phoenix, Arizona; the Department of Neurology (G.T.), University of Athens School of Medicine, Athens, Greece; the Department of Medicine (Neurology) (M.S.), University of Alberta, Canada; the Division of Neurology, Department of Medicine (V.K.S.), National University Hospital, Singapore; the University of Santo Tomas (A.Y.L.), Manila, Philippines; and the Department of Clinical Neuroscience (M.D.H.), University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada.
Correspondence to Georgios Tsivgoulis, MD, Iofontos 2, 11634-Athens, Greece. E-mail tsivgoulisgiorg{at}yahoo.gr
| Abstract |
|---|
|
|
|---|
Methods Consecutive patients with acute ischemic stroke resulting from intracranial artery occlusion were treated with standard intravenous tPA and assessed with 2-MHz transcranial Doppler for arterial recanalization. Early arterial recanalization was determined with previously validated Thrombolysis in Brain Ischemia flow grading system at 120 minutes after tPA bolus. Functional outcome at 3 months was evaluated using the modified Rankin Scale.
Results A total of 351 patients received intravenous tPA (mean age: 68.7±13.4 years, median National Institutes of Health Stroke Scale score 16.5). Patients with complete recanalization (n=94) had lower mean pretreatment SBP values (152±23 mm Hg) than patients with incomplete or absent recanalization (n=257, 160±22 mm Hg, P=0.010). Pretreatment SBP levels were inversely associated with complete recanalization (OR per 10-mm Hg increase: 0.85; 95% CI: 0.74 to 0.98, P=0.022) after adjustment for demographics, risk factors, stroke severity, pretreatment Thrombolysis in Brain Ischemia grades, and continuous versus intermittent exposure to transcranial Doppler. Although patients with poor functional 3-month outcomes (modified Rankin Scale >2) had higher pretreatment SBP values (160±25 mm Hg) than functionally independent patients (154±20 mm Hg, P=0.027), pretreatment SBP levels were not independently associated with functional outcome on multivariable analysis. Age, complete recanalization, baseline National Institutes of Health Stroke Scale score, and time from symptom onset to tPA bolus were independent (P<0.05) predictors of 3-month outcome.
Conclusion Higher pretreatment SBP levels are associated with poor recanalization in patients with acute stroke treated with intravenous tPA.
Key Words: blood pressure outcome recanalization stroke thrombolysis
| Introduction |
|---|
|
|
|---|
| Methods |
|---|
|
|
|---|
On arrival in the emergency room, patients underwent standard neurologic examination, electrocardiogram, blood chemistry, and noncontrast CT before tPA administration. Clinical status at baseline was assessed with the National Institutes of Health Stroke Scale (NIHSS) by a certified neurologist. Pretreatment SBP was measured using automated cuffs. When SBP exceeded 185 mm Hg, antihypertensive agents were given (first-line agents: labetalol or nicardipine).
All patients received intravenous tPA according to standard criteria.13 The patients received either continuous or intermittent 2-MHz TCD assessment of recanalization within 2 hours of tPA bolus. All patients had evidence of obstructive residual flow signals in proximal intracranial arteries on baseline TCD assessment before tPA bolus. An experienced physiciansonographer diagnosed these occlusions using previously validated criteria, including the Thrombolysis in Brain Ischemia (TIBI) flow-grading system, if grades 0 to 3 were present.14,15 Concomitant and persisting severe stenosis or occlusion of the proximal internal carotid artery was established by carotid duplex ultrasonography or by angiography. In all patients with anterior circulation occlusions, transducers were positioned over the temporal bone with a standard head frame (Marc series; Spencer Technologies). The depth with the worst residual flow signal as measured on the TIBI scale was selected for display. An insonation depth of 45 mm or more was used for the identification of proximal (ie, M1) MCA occlusion and depths of 30 to 45 mm for presumed distal occlusions (ie, M2). Contralateral ACA (if available) or ipsilateral MCA were used as comparison vessels in case of ACA occlusions. In patients with evidence of posterior circulation occlusions (vertebral or basilar artery), TIBI flow grade was determined through the transforaminal window after analyzing the worst flow signal determined at the presumed occlusion site. Normal vertebral artery (if available) was used as the comparison vessel in cases of basilar artery occlusion. TIBI grade was compared with the contralateral vertebral or the basilar artery in patients with suspected vertebral artery occlusions.
Early arterial recanalization was determined using the TIBI system by the site investigators who gave t-PA and monitored residual blood flow signals. Recanalization was determined 2 hours after t-PA bolus. Complete recanalization was diagnosed if flow improved to TIBI grades 4 to 5 and partial recanalization was identified if flow improved by one grade or more from the baseline but not to grades 4 to 5 on the TIBI scale. Patients with reocclusion within 2 hours were diagnosed as having persisting occlusion 2 hours after tPA bolus. In patients with concomitant and persisting severe stenosis or occlusion of the proximal internal carotid artery, complete recanalization of the MCA was considered to have been achieved if TCD showed low-resistance waveforms (TIBI 2 or greater) over both M1 and M2 segments with an improvement in mean flow velocity to more than 20 cm/sec.12,13 Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria.16 Safety was assessed by detecting symptomatic intracerebral hemorrhage (sICH) within 72 hours of the onset of stroke. sICH was defined as brain imaging evidence of intracerebral hemorrhage with clinical worsening by NIHSS score increase of
4 points.12 Modified Rankin scores (mRS) were obtained at 3 months and poor functional outcome was defined as mRS >2. The treating physicians assessed neurologic status during TCD monitoring, graded intracerebral hemorrhage as symptomatic, and evaluated functional outcome at 3 months without knowledge of random assignment to continuous or intermittent TCD monitoring.
Statistical Analysis
Statistical comparisons were performed between subgroups of patients using the
2 test, Fisher exact test, unpaired t test, and Mann-Whitney U test as indicated for dichotomous or continuous variables. Continuous variables were compared between 3 or more subgroups by use of one-way analysis for variance. Bonferroni correction for multiple comparisons was applied as indicated. Multivariable analyses were performed with the use of logistic regression to identify predictor variables of complete vessel recanalization 2 hours after tPA bolus and good functional outcome (mRS score 0 to 2) at 3 months. Initially, univariable analyses of potential predictors (demographic characteristics, stroke risk factors, Trial of Org 10172 in Acute Stroke Treatment subtypes, baseline TIBI grade, NIHSS score, pretreatment SBP and serum glucose, continuous versus intermittent exposure to TCD ultrasonography) were performed. To maximize sensitivity, those variables with a univariable association of P<0.2 were included as candidates into a multivariable logistic regression model and then removed by the backward stepwise selection procedure. To confirm the robustness of multivariable models, we repeated all multivariable analyses using a forward selection procedure. Predictor variables that were significant at P<0.05 were retained in the multivariable model. Associations are presented as OR with corresponding 95% CIs. Because the absence of symmetric counterpart vessels in patients with vertebral artery, basilar artery, and ACA occlusions might be a source of discrepancies in the calculation of a valid TIBI score, all analyses were repeated after excluding the former patient subgroups. The Statistical Package for Social Science (version 11.5 for Windows; SPSS Inc., Chicago, IL) was used for statistical analyses.
| Results |
|---|
|
|
|---|
Complete recanalization at 2 hours after t-PA bolus was seen in 94 patients (26.8%). Partial recanalization was identified in 98 patients, whereas persisting occlusion was documented in 159 cases. Arterial reocclusion was present in 51 patients (15%). Pretreatment SBP values were different among patients with complete recanalization (152±23 mm Hg), reocclusion (157±20 mm Hg), and persisting occlusion (161±22 mm Hg; F=3.989, df=2, P=0.019). The pretreatment SBP levels of patients with atrial fibrillation (157±23 mm Hg) were similar (P>0.5) to patients without any history or electrocardiographic evidence of atrial fibrillation (159±22 mm Hg). SBP values did not differ among patients with large artery atherosclerotic stroke (157±25 mm Hg), cardioembolic stroke (158±23 mm Hg), infarct of undetermined cause (157±19 mm Hg), and infarct of other determined cause (156±26 mm Hg; F=0.054, df=3, P> 0.9). Although there was no difference (P>0.2) in pretreatment SBP levels by various TIBI grades before tPA bolus, higher pretreatment mean SBP levels were documented in patients with persisting high resistance occlusions (TIBI grade 0 to 1; 161±21 mm Hg) 2 hours after the t-PA bolus compared with patients with normal or low resistance residual flow (TIBI grade 2 to 5; 154±22 mm Hg; P=0.009) 2 hours after the initiation of thrombolytic treatment.
The following factors were associated with complete recanalization on univariable analyses (P<0.2, Table 1): hypertension, diabetes mellitus, exposure to 2-hour TCD monitoring, pretreatment SBP and serum glucose levels, baseline TIBI grades, and baseline NIHSS scores. The distribution of Trial of Org 10172 in Acute Stroke Treatment subtypes in patients with complete recanalization was similar to patients with persisting occlusion or incomplete recanalization (Table 1). In a multivariable logistic regression model (Table 2) complete recanalization was more likely in patients exposed to continuous TCD monitoring (OR: 3.54; 95% CI: 1.68 to 7.46) and less likely among patients with baseline TIBI grade <2 (OR: 0.47; 95% CI: 0.25 to 0.87), higher baseline serum glucose levels (OR per additional 10 mg/dL: 0.94; 95% CI: 0.90 to 0.99), higher SBP (OR per additional 10 mm Hg: 0.85; 95% CI: 0.74 to 0.98), and higher NIHSS (OR per one-point increase: 0.94; 95% CI: 0.88 to 0.99). The multivariable models internal validity was assessed using the Hosmer-Lemeshow goodness-of-fit test (
2 statistic=10.433, df=8, P=0.236) that indicated the model was internally valid.
|
|
All analyses were repeated after excluding the patients with basilar artery, ACA, and vertebral artery occlusions (n=9). Higher pretreatment SBP levels were documented in patients with persisting occlusion or incomplete recanalization (160±23 mm Hg, n=251) than in patients with complete comparison (151±22 mm Hg, n=91, P=0.016). In the former subgroup of patients (including only MCA or terminal internal cerebral artery occlusions), the following factors were independently (P<0.05) associated with vessel recanalization on the multivariate analyses: continuous TCD monitoring (OR: 3.81; 95% CI: 1.76 to 8.23), baseline TIBI grade <2 (OR: 0.49; 95% CI: 0.26 to 0.95), baseline serum glucose levels (OR per additional 10 mg/dL: 0.94; 95% CI: 0.89 to 0.99), pretreatment SBP (OR per additional 10 mm Hg: 0.85; 95% CI: 0.73 to 0.98), baseline NIHSS (OR per one-point increase: 0.93; 95% CI: 0.87 to 0.99), and tandem internal carotid artery/MCA lesions (OR: 0.16; 95% CI: 0.05 to 0.49). Finally, exclusion of patients with reocclusion from the multivariable model did not affect the independent relationship between pretreatment SBP and recanalization (OR per additional 10 mm Hg: 0.85; 95% CI: 0.74 to 0.96; P=0.010).
The rate of complete recanalization 2 hours after the tPA bolus was 14% in patients with higher pretreatment SBP (>185 mm Hg), 25% in cases with SBP of 140 to 185 mm Hg, and 36% in patients with SBP <140 mm Hg (P=0.042, Table 3). No significant (P>0.4) differences were documented concerning pretreatment SBP values between patients with proximal (157±22 mm Hg) and distal (159±23 mm Hg) MCA occlusion as well as between patients with tandem MCA/internal carotid artery (158±23 mm Hg) occlusion and isolated MCA (158±22 mm Hg) occlusion. sICH occurred in 28 patients (8.0%). The rate of sICH was similar in patients with continuous (n=23 [8%]) and intermittent TCD monitoring (n=5 [7%], P>0.6). The baseline SBP levels in the subgroup of sICH (157±27 mm Hg) were similar to patients without sICH (158±22 mm Hg; P>0.8).
|
At 3 months, mRS scores were available for 292 patients (83%). Pretreatment SBP levels did not differ (P>0.5) between patients with complete (157±20 mm Hg) and incomplete 3-month (159±23 mm Hg) follow up. A total of 137 (47%) patients became functionally independent (mRS score
2), whereas 61 (21%) patients had died during the follow-up period. Functionally dependent (mRS score 3 to 5) or dead patients had higher pretreatment mean SBP levels (160±25 mm Hg) and lower complete recanalization rates (13%) 2 hours after t-PA bolus in comparison to subjects with good functional outcome (154±20 mm Hg and 47%, respectively; P<0.05). The multivariable logistic regression model (Table 4) showed age, complete recanalization, baseline NIHSS, and elapsed time from symptom onset to t-PA bolus infusion were independent (P<0.05) predictors of good outcome at 3 months. Pretreatment SBP was not independently associated with outcome on multivariable logistic regression analyses (P>0.3) both for the whole study group and after exclusion of patients with vertebral artery, MCA, and ACA occlusions.
|
| Discussion |
|---|
|
|
|---|
Mattle et al have recently investigated the potential association between the course of blood pressure values and the grades of recanalization determined using Thrombolysis in Myocardial Infarction criteria in a series of patients treated with intraarterial thrombolysis.10 Interestingly, larger SBP decreases were documented in subjects with successful recanalization, whereas a persistent elevation of SBP values inversely correlated to the degree of recanalization.10 However, it should be noted that the blood pressure levels before thrombolysis did not differ between patients with adequate and inadequate recanalization. This discrepancy with our results may be associated with the longer time window used for intraarterial thrombolytic treatment, different methods of blood pressure recording (automatically versus manually), and the different criteria for determination of vessel recanalization (Thrombolysis in Myocardial Infarction grades versus TIBI grades) between the 2 studies.
We hypothesize that the inverse relationship between increased pretreatment SBP levels and vessel patency might be attributable to the following different pathophysiological mechanisms.
Association of Increased Pretreatment Systolic Blood Pressure Levels With Cerebral Edema
In experimental studies, poststroke hypertension increased bloodbrain barrier permeability and exacerbated cerebral edema during the first hours of focal brain ischemia.17,18 SBP >180 mm Hg was an independent predictor of cerebral edema in the placebo arm of the Lubezulole-International-9 trial.19 Furthermore, elevated 24-hour SBP levels documented by means of oscillometric blood pressure-monitoring devices were also associated with subsequent cerebral edema formation in a series of hyperacute patients with stroke.20 Interestingly, in the present study, higher pretreatment SBP values were observed in patients with persisting high-resistance occlusions. Because brain swelling is associated with increased resistance to residual blood flow,21,22 it may be assumed that high pretreatment blood pressure values by exacerbating early brain swelling could have a possible detrimental effect on vessel recanalization. In addition, cytotoxic edema can impede microcirculation in the core of infarction during the first 3 hours of ictus as seen in animal models of the MCA occlusion.23 In our study, the baseline stroke severity was high (median NIHSS score 16 points). Thus, patients with future malignant MCA infarction in which mass effect and extreme elevations of intracranial pressure could develop within the first hours of brain ischemia were included in the present analyses. On the other hand, it can be argued that at the time of thrombolysis, it is too early for mass effect to develop and thus is unlikely that early brain swelling might have increased intracranial pressure and impeded residual cerebral blood flow at such a narrow time window from stroke onset.
Elevated Pretreatment Blood Pressure and Increased Baseline Thrombus Burden
Although it is plausible that larger thrombi may lead to higher systemic blood pressure values, in our study, there was no association between proximity or tandem nature of occlusions and pretreatment SBP. Even if such correlation exists, it may be overshadowed by successful recanalization that was a stronger outcome predictor in our analyses.
Association of Elevated Pretreatment Systolic Blood Pressure Levels With Impaired Endogenous Capacity for Fibrinolysis
Increased SBP values have been correlated with higher fibrinogen levels,24 whereas the activation of the endogenous fibrinolytic system by acute release of t-PA is markedly impaired in hypertensive patients.25,26 Moreover, in animal studies, increased intraluminal pressure decreased t-PA expression and release in human umbilical veins or cultured endothelial cells.27,28 Furthermore, recent evidence have shown that antihypertensive treatment with either anangiotensin-converting enzyme inhibitor or a calcium channel blocker endothelial fibrinolytic function and enhanced endogenous fibrinolysis.29 Although fibrinogen levels and fibrinolytic activity were not measured in our population, it may be hypothesized that higher pretreatment SBP levels may have some detrimental effect on vessel recanalization by hampering the endogenous capacity for fibrinolysis.
Certain limitations of the present report should be acknowledged. First, diastolic blood pressure was not recorded and consequently the association between certain blood pressure components (diastolic blood pressure, pulse pressure, mean arterial pressure) and vessel recanalization could not be evaluated. Second, we did not obtain details as to how effectively baseline SBP >185 mm Hg was treated. Furthermore, SBP values were not recorded during and at the end of the TCD monitoring and thus, the potential association of SBP course or periprocedural SBP levels with the grade of vessel recanalization cannot be assessed in the present data set. Third, the TIBI grading system might not be suitable for grading the occlusions of vessels without strictly symmetric counterparts (ACA/vertebral artery/basilar artery). However, all analyses were repeated after excluding the former group of patients (n=9) and practically identical results were obtained. Fourth, mRS scores at 3 months were unavailable in 17% of the study population and this methodological shortcoming should also be taken into consideration. Of note, however, pretreatment SBP levels were similar among patients with complete and incomplete follow up. Thus, it is unlikely that the exclusion of patients with incomplete follow up from the analyses investigating independent predictors of stroke outcome may have substantially influenced our findings. Fifth, our analysis is retrospective and residual confounding is possible.
In conclusion, the present study supports an inverse relationship between increased pretreatment SBP levels and tPA-induced recanalization of the initially occluded vessel in patients with acute stroke. Additional data are needed to clarify this intriguing albeit complex relationship and to determine whether markedly elevated blood pressure levels after acute arterial occlusion are a risk factor or a risk marker for subsequently inadequate recanalization after systemic thrombolysis.
| Acknowledgments |
|---|
Dr Tsivgoulis is recipient of a neurosonology fellowship grant from the Neurology Department of Eginition Hospital, University of Athens School of Medicine, Athens, Greece. Dr Sharma received financial grant for his fellowship from National Healthcare Group and National University Hospital, Singapore. Dr Lao received fellowship grant from the Neurology Department of Saint Thomas Hospital and Tan Yan Kee Foundation, Manila, Philippines. Dr Hill holds the Heart & Stroke Foundation of Alberta/NWT/NU Professorship in Stroke Research.
Disclosures
None.
Received August 22, 2006; revision received September 25, 2006; accepted October 3, 2006.
| References |
|---|
|
|
|---|
2. Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment With Alteplase to Reverse Stroke (STARS) study. JAMA. 2000; 283: 11451150.
3. Demchuk AM, Tanne D, Hill MD, Kasner SE, Hanson S, Grond M, Levine SR, for the Multicentre tPA Stroke Survey Group. Predictors of good outcome after intravenous tPA for acute ischemic stroke. Neurology. 2001; 57: 474480.
4. Molina CA, Alexandrov AV, Demchuk AM, Saqqur M, Uchino K, Alvarez-Sabin J; CLOTBUST Investigators. Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator. Stroke. 2004; 35: 151156.
5. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke. 1997; 28: 21192125.
6. Alexandrov AV, Burgin SW, Demchuk AM, El-Mitwalli A, Grotta JC. Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement. Circulation. 2001; 103: 28972902.
7. Christou I, Alexandrov AV, Burgin WS, Wojner AW, Felberg RA, Malkoff M, Grotta JC. Timing of recanalization after tissue plasminogen activator therapy determined by transcranial Doppler correlates with clinical recovery from ischemic stroke. Stroke. 2000; 31: 18121816.
8. Molina CA, Montaner J, Abilleira S, Arenillas JF, Ribo M, Huertas R, Romero F, Alvarez-Sabin J. Time course of tissue plasminogen activator-induced recanalization in acute cardioembolic stroke: a casecontrol study. Stroke. 2001; 32: 28212827.
9. Labiche LA, Al-Senani F, Wojner AW, Grotta JC, Malkoff M, Alexandrov AV. Is the benefit of early recanalization sustained at 3 months? A prospective cohort study. Stroke. 2003; 34: 695698.
10. Mattle HP, Kappeler L, Arnold M, Fischer U, Nedeltchev K, Remonda L, Jakob SM, Schroth G. Blood pressure and vessel recanalization in the first hours after ischemic stroke. Stroke. 2005; 36: 264268.
11. Alexandrov AV, Demchuk AM, Burgin WS, Robinson DJ, Grotta JC; CLOTBUST Investigators. Ultrasound-enhanced thrombolysis for acute ischemic stroke: phase I. Findings of the CLOTBUST trial. J Neuroimaging. 2004; 14: 113117.[CrossRef][Medline] [Order article via Infotrieve]
12. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moye LA, Hill MD, Wojner AW; CLOTBUST Investigators. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004; 351: 21702178.
13. Adams HP Jr, Adams RJ, Brott T, del Zoppo GJ, Furlan A, Goldstein LB, Grubb RL, Higashida R, Kidwell C, Kwiatkowski TG, Marler JR, Hademenos GJ; Stroke Council of the Am Stroke Association. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke. 2003; 34: 10561083.
14. Demchuk AM, Christou I, Wein TH, Felberg RA, Malkoff M, Grotta JC, Alexandrov AV. Accuracy and criteria for localizing arterial occlusion with transcranial Doppler. J Neuroimaging. 2000; 10: 112.[Medline] [Order article via Infotrieve]
15. Burgin WS, Malkoff M, Demchuk AM, Felberg RA, Christou I, Grota JC, Alexandrov AV. Transcranial Doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke. Stroke. 2000; 31: 11281132.
16. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24: 3541.
17. Yamaguchi S, Kobayashi S, Yamashita K, Kitani M. Pial arterial pressure contribution to early ischemic brain edema. J Cereb Blood Flow Metab. 1989; 9: 597602.[Medline] [Order article via Infotrieve]
18. Durward QJ, Del Maestro RF, Amacher AL, Farrar JK. The influence of systemic arterial pressure and intracranial pressure on the development of cerebral vasogenic edema. J Neurosurg. 1983; 59: 803809.[CrossRef][Medline] [Order article via Infotrieve]
19. Krieger DW, Demchuk AM, Kasner SE, Jauss M, Hantson L. Early clinical and radiological predictors of fatal brain swelling in ischemic stroke. Stroke. 1999; 30: 287292.
20. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N, Synetos A, Kotsis V, Vassilopoulos D, Mavrikakis M. Association between 24-h blood pressure monitoring variables and brain oedema in patients with hyperacute stroke. J Hypertens. 2003; 21: 21672173.[CrossRef][Medline] [Order article via Infotrieve]
21. Mayer SA, Thomas CE, Diamond BE. Asymmetry of intracranial hemodynamics as an indicator of mass effect in acute intracerebral hemorrhage. A transcranial Doppler study. Stroke. 1996; 27: 17881792.
22. Treib J, Becker SC, Grauer M, Haass A. Transcranial Doppler monitoring of intracranial pressure therapy with mannitol, sorbitol and glycerol in patients with acute stroke. Eur Neurol. 1998; 40: 212219.[CrossRef][Medline] [Order article via Infotrieve]
23. Roussel SA, van Bruggen N, King MD, Gadian DG. Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI. J Cereb Blood Flow Metab. 1995; 15: 578586.[Medline] [Order article via Infotrieve]
24. Lip GY, Blann AD, Jones AF, Lip PL, Beevers DG. Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. Am J Cardiol. 1997; 80: 15661571.[CrossRef][Medline] [Order article via Infotrieve]
25. Hrafnkelsdottir T, Wall U, Jern C, Jern S. Impaired capacity for endogenous fibrinolysis in essential hypertension. Lancet. 1998; 352: 15971598.[CrossRef][Medline] [Order article via Infotrieve]
26. Hrafnkelsdottir T, Ottosson P, Gudnason T, Samuelsson O, Jern S. Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension. Hypertension. 2004; 44: 300304.
27. Sjogren LS, Doroudi R, Gan L, Jungersten L, Hrafnkelsdottir T, Jern S. Elevated intraluminal pressure inhibits vascular tissue plasminogen activator secretion and downregulates its gene expression. Hypertension. 2000; 35: 10021008.
28. Ulfhammer E, Ridderstrale W, Andersson M, Karlsson L, Hrafnkelsdottir T, Jern S. Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular endothelial cells. J Hypertens. 2005; 23: 15511557.[Medline] [Order article via Infotrieve]
29. Ridderstrale W, Ulfhammer E, Jern S, Hrafnkelsdottir T. Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy. Hypertension. 2006; 47: 686691.
This article has been cited by other articles:
![]() |
G. Tsivgoulis, J. L. Frey, M. Flaster, V. K. Sharma, A. Y. Lao, S. L. Hoover, W. Liu, E. Stamboulis, A. W. Alexandrov, M. D. Malkoff, et al. Pre-Tissue Plasminogen Activator Blood Pressure Levels and Risk of Symptomatic Intracerebral Hemorrhage Stroke, November 1, 2009; 40(11): 3631 - 3634. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Ahmed, N. Wahlgren, M. Brainin, J. Castillo, G. A. Ford, M. Kaste, K. R. Lees, D. Toni, and for the SITS Investigators Relationship of Blood Pressure, Antihypertensive Therapy, and Outcome in Ischemic Stroke Treated With Intravenous Thrombolysis: Retrospective Analysis From Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) Stroke, July 1, 2009; 40(7): 2442 - 2449. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Tsivgoulis, K. Voumvourakis, and E. Stamboulis Sex-Differences in the Impact of Metabolic Syndrome on Tissue Plasminogen Activator-Induced Recanalization Stroke, April 1, 2009; 40(4): e100 - e100. [Full Text] [PDF] |
||||
![]() |
O. Y. Bang, J. L. Saver, J. R. Alger, S. Starkman, B. Ovbiagele, D. S. Liebeskind, and For the UCLA Collateral Investigators Determinants of the distribution and severity of hypoperfusion in patients with ischemic stroke Neurology, November 25, 2008; 71(22): 1804 - 1811. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Martin-Schild, H. Hallevi, K. C. Albright, A. M. Khaja, A. D. Barreto, N. R. Gonzales, J. C. Grotta, and S. I. Savitz Aggressive Blood Pressure-Lowering Treatment Before Intravenous Tissue Plasminogen Activator Therapy in Acute Ischemic Stroke Arch Neurol, September 1, 2008; 65(9): 1174 - 1178. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. V. Alexandrov, R. Mikulik, M. Ribo, V. K. Sharma, A. Y. Lao, G. Tsivgoulis, R. M. Sugg, A. Barreto, P. Sierzenski, M. D. Malkoff, et al. A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound-Activated Perflutren-Lipid Microspheres for Acute Ischemic Stroke Stroke, May 1, 2008; 39(5): 1464 - 1469. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Tsivgoulis, V. K. Sharma, S. L. Hoover, A. Y. Lao, A. A. Ardelt, M. D. Malkoff, and A. V. Alexandrov Applications and Advantages of Power Motion-Mode Doppler in Acute Posterior Circulation Cerebral Ischemia Stroke, April 1, 2008; 39(4): 1197 - 1204. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Stroke Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2007 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |