Acute ischemic stroke (AIS) affects over 700,000 Americans every year and is the leading
cause of long-term disability. Early neurological deterioration after AIS typically occurs
within 72 hours of stroke onset and affects 30% of all stroke patients, who have a higher
rate of death or poor outcome. Several mechanisms account for early neurological
deterioration, including hemorrhagic conversion, systemic illness, cerebral edema, and
seizure, but the most common cause is extension of the stroke into the "penumbra," a region
of salvageable brain tissue surrounding the core of irreversible ischemic infarct. The
penumbra is tenuously perfused by collateral blood vessels. AIS management is primarily
focused on recanalizing the occluded artery causing the stroke, but an alternative and
relatively unexplored approach is optimization of collateral blood flow.
Over 60% of AIS patients present with a transient acute hypertensive response, which is
theorized to be the result of either increased sympathoadrenal tone, poorly controlled
underlying hypertension, or an unknown stroke-specific mechanism related to augmenting
cerebral perfusion through collateral blood flow. Epidemiological data suggests worse stroke
outcomes are associated with extremes of sustained hypo- or hypertension, which has led to
dozens of clinical trials involving over 20,000 patients to determine if pharmacologically
lowering blood pressure after AIS is beneficial. The results have been persistently neutral
or negative. In contrast, there have been no major clinical trials on the efficacy of using
vasopressor medications to maintain or increase baseline blood pressure after AIS, despite
promising preclinical data and pilot studies that showed no increase in cerebral hemorrhage
or edema. The only randomized trial of vasopressor use after AIS demonstrated an improvement
in clinical outcomes, but there was no difference in mean blood pressure between the control
and intervention arms, suggesting the beneficial effect was not exclusively related to
induced hypertension. One possibility is that the vasopressor reduced blood pressure
variability, which preliminary data has shown to be detrimental after AIS, although that
aspect of neurovascular coupling has not been adequately studied in the acute phase after
AIS.
The reliance on IV vasopressors, which are only administered in the intensive care unit, is a
fundamental limitation of prior research. An alternative, but untested, approach is to use
the oral vasopressor midodrine hydrochloride. We hypothesize that frequent midodrine dosing
after AIS can optimize collateral blood flow and help salvage the ischemic penumbra. The
objective of this study is to develop tools to quantify midodrine's effect on blood pressure
and the ischemic penumbra.