Spontaneous intracerebral hemorrhage (ICH) comprises approximately 10% of all strokes with an annual incidence of approximately 15/100,000. Current treatment results are disappointing. Initial mortality remains high and survivors often have significant residual disability. New therapeutic approaches are difficult to pursue because little is known about the pathophysiologic mechanisms of brain injury. The goal of this research is to determine whether pharmacologic reduction in mean arterial pressure within 24 hours after acute ICH produces or exacerbates ischemia. We will test the specific null hypothesis: Pharmacologic blood pressure reduction of 15+5% in patients with spontaneous supratentorial ICH does not produce regional cerebral ischemia potentially severe enough to cause tissue injury. We will perform this Specific Aim: Thirty patients with acute ICH within 24 hours of onset and initial mean arterial pressure of 120-150 mm Hg who have just completed measurements of regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO2), regional oxygen extraction fraction (rOEF) and regional cerebral venous oxygen content (rCvO2) using positron emission tomography (PET) as part of Project 3 will be randomized into 3 groups of 10 patients each. One groups will receive no antihypertensive medication. The second and third groups will receive either labetalol (Group II) or nicardipine (Group III) to lower MAP by 15 plus minus % within 60 minutes. We will repeat PET measurements after target MAP is reached or, for the control group, approximately 60 minutes later. We will determine the effect of pharmacologic reduction in MAP on average hemispheric CBF and we will also determine if there re critical shifts from safe to dangerous or lethal ranges of rCBF, rCMRO2 and rCvO2. This research will provide fundamentally important pathophysiologic information about the possible role of iatrogenic ischemic in producing secondary brain injury in patients with ICH which will be of enormous value in planning future therapeutic investigations.

Project Start
2000-06-01
Project End
2001-05-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2000
Total Cost
$121,168
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
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
Lee, J J; Powers, W J; Faulkner, C B et al. (2013) The Kety-Schmidt technique for quantitative perfusion and oxygen metabolism measurements in the MR imaging environment. AJNR Am J Neuroradiol 34:E100-2
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
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
Powers, William J; Haas, Richard H; Le, Thuy et al. (2011) Platelet mitochondrial complex I and I+III activities do not correlate with cerebral mitochondrial oxidative metabolism. J Cereb Blood Flow Metab 31:e1-5
Powers, William J; Videen, Tom O; Markham, Joanne et al. (2011) Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic. J Cereb Blood Flow Metab 31:1223-8
Zazulia, Allyson R; Videen, Tom O; Diringer, Michael N et al. (2011) Poor correlation between perihematomal MRI hyperintensity and brain swelling after intracerebral hemorrhage. Neurocrit Care 15:436-41
Powers, William J; Zazulia, Allyson R (2010) PET in Cerebrovascular Disease. PET Clin 5:83106
Powers, William J (2010) Intracerebral hemorrhage and head trauma: common effects and common mechanisms of injury. Stroke 41:S107-10
Sampson, Tomoko R; Dhar, Rajat; Diringer, Michael N (2010) Factors associated with the development of anemia after subarachnoid hemorrhage. Neurocrit Care 12:4-9

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