: Thrombolysis using intravenous tissue Plasminogen Activator (rtPA) is the only proven therapy for Acute Ischemic Stroke, but it is only appropriate for some patients. The long-term goal of this proposal is to investigate the use of induced Hypertension as an alternative means of Cerebral Reperfusion. The rationale assumes the presence of an Ischemic Penumbra, a region of hypoperfused brain that is still viable and able to be rescued. Until recently, delineation of the Ischemic Penumbra in clinical practice has been impractical. Diffusion-Weighted MRI (DWI) allows early detection of Ischemic injury and Perfusion-Weighted MRI (PWI) shows areas of relative Cerebral Hypoperfusion. The DWI/PWI mismatch (in patients with PWI > DWI) can be functionally defined as the Ischemic Penumbra. Pharmacological elevation of blood pressure may increase cerebral blood flow to this region, and allow recovery of function. Before a double-blind, placebo-controlled clinical trial can be undertaken; several scientific issues need to be addressed. We propose a pilot clinical trial using DWI/PWI to investigate the physiology of induced Hypertension, and also study whether MRI can be used as a means of selecting patients likely to respond to treatment, as improved selection will allow more efficient trials later. Patients presenting within 12 hours of onset of stroke will be treated with a protocol of intravenous phenylephrine to increase mean arterial pressure to a maximum of 30% over baseline. Patients will have DWI/PWI studies performed before and during induced Hypertension, as well as 1-month follow-up. Serial neurological assessments (including the NIH stroke scale) will be performed by an investigator blinded to the imaging studies.
The specific aims of this proposal are to: 1) determine the proportion of patients who have clinical improvement or serious adverse events related to induced Hypertension; 2) determine if the presence of DWI/PWI mismatch identifies patients likely to respond to induced Hypertension. We hypothesize that patients with mismatch are more likely to respond than are patients with other MRI patterns; and 3) correlate changes in neurological deficit with changes in MRI during induced Hypertension. An association of improved function, with reduction in the volume of mismatch, will support the proposed physiology.
