Hypertension is one of the most significant risk factors for ischemic stroke. Long term treatment of hypertension after stroke has been shown to reduce the incidence of recurrent stroke by 28% and major cardiovascular complications by 26%. However, in the setting of acute ischemic stroke it has been difficult to determine the appropriate treatment of elevated blood pressure due to the overwhelming concern that lowering blood pressure in this setting might worsen cerebral ischemia. These concerns are based primarily on studies of CBF in animal models. Very few studies of the effect of pharmacological reduction of elevated blood pressure on CBF following acute ischemic stroke in humans have been done and they do not provide adequate data to settle this issue. The goal of this research project is to determine the effect of controlled, graded pharmacologic reduction of blood pressure on rCBF following acute ischemic stroke using positron emission tomography (PET) and to carefully monitor the clinical effects and safety of treatment. This specific null hypothesis will be tested: Pharmacological reduction of mean arterial blood pressure (MAP) by 15 +/- 5 mm Hg in patients with a recent cerebral infarction and elevated blood pressure does not produce a statistically significant reduction in regional cerebral blood flow.
This Specific Aim will be carried out: Between day 3-14 after onset, sixty patients with a hemispheric cerebral infarction and mean arterial blood pressure of 120-150 mm Hg will undergo a detailed neurological examination and measurements of rCBF, regional cerebral metabolic rate (rCMRO2), and regional oxygen extraction fraction (rOEF) using PET. Blood pressure will then be lowered pharmacologically in two steps of 7.5 +/- 5 mm Hg each using intravenous labetalol. The neurological examination and CBF measurements will be repeated after each step. This study is not designed to provide data on whether blood pressure in the acute setting improves outcome. This can only be done by randomized treatment trials with clinical outcome measures. These data can, however, be used to help design such a trial and, in the meantime, provide helpful guidelines when reduction in arterial pressure is deemed to be necessary for other reasons. This study will provide esssential information necessary to translate data from animal studies into treatment for human cerebrovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS035966-10
Application #
7553655
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
10
Fiscal Year
2007
Total Cost
$201,820
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Dhar, Rajat; Zazulia, Allyson R; Derdeyn, Colin P et al. (2017) RBC Transfusion Improves Cerebral Oxygen Delivery in Subarachnoid Hemorrhage. Crit Care Med 45:653-659
Dhar, Rajat; Diringer, Michael N (2015) Relationship between angiographic vasospasm, cerebral blood flow, and cerebral infarction after subarachnoid hemorrhage. Acta Neurochir Suppl 120:161-5
Diringer, Michael N (2013) New trends in hyperosmolar therapy? Curr Opin Crit Care 19:77-82
Delgado Almandoz, Josser E; Jagadeesan, Bharathi D; Refai, Daniel et al. (2012) Diagnostic yield of computed tomography angiography and magnetic resonance angiography in patients with catheter angiography-negative subarachnoid hemorrhage. J Neurosurg 117:309-15
Dhar, Rajat; Scalfani, Michael T; Blackburn, Spiros et al. (2012) Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke 43:1788-94
Dhar, Rajat; Scalfani, Michael T; Zazulia, Allyson R et al. (2012) Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage. J Neurosurg 116:648-56
Diringer, Michael N; Scalfani, Michael T; Zazulia, Allyson R et al. (2012) Effect of mannitol on cerebral blood volume in patients with head injury. Neurosurgery 70:1215-8; discussion 1219
Dhar, Rajat; Diringer, Michael (2012) Statins and anti-inflammatory therapies for subarachnoid hemorrhage. Curr Treat Options Neurol 14:164-74
Shah, Manish N; Botros, James A; Pilgram, Thomas K et al. (2012) Borden-Shucart Type I dural arteriovenous fistulas: clinical course including risk of conversion to higher-grade fistulas. J Neurosurg 117:539-45
Scalfani, Michael T; Dhar, Rajat; Zazulia, Allyson R et al. (2012) Effect of osmotic agents on regional cerebral blood flow in traumatic brain injury. J Crit Care 27:526.e7-12

Showing the most recent 10 out of 20 publications