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.
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