Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia.
OBJECTIVE
In focal ischemic cortex, cerebral blood flow autoregulation is impaired, and perfusion passively follows blood pressure variations. Although it is generally agreed that profound hypotension is harmful in acute stroke, the hemodynamic and metabolic impact of increased blood pressure on the ischemic core and penumbra are less well understood. We, therefore, tested whether pharmacologically induced hypertension improves cerebral blood flow and metabolism and tissue outcome in acute stroke using optical imaging with high spatiotemporal resolution.


METHODS
Cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen were measured noninvasively using simultaneous multispectral reflectance imaging and laser speckle flowmetry during distal middle cerebral artery occlusion in mice. Hypertension was induced by phenylephrine infusion starting 10 or 60 minutes after ischemia to raise blood pressure by 30% for the duration of ischemia; control groups received saline infusion.


RESULTS
Mild induced hypertension rapidly increased cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen in both the core and penumbra and prevented the expansion of cerebral blood flow deficit during 1 hour distal middle cerebral artery occlusion. Induced hypertension also diminished the deleterious effects of periinfarct depolarizations on cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen without altering their frequency. Consistent with this, mild induced hypertension reduced infarct volume by 48% without exacerbating tissue swelling when measured 2 days after 1 hour transient distal middle cerebral artery occlusion.


CONCLUSIONS
Our data suggest that mild induced hypertension increases collateral cerebral blood flow and oxygenation and improves cerebral metabolic rate of oxygen in the core and penumbra, supporting its use as bridging therapy in acute ischemic stroke until arterial recanalization is achieved.
Shin
Hwa Kyoung
HK
Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Nishimura
Masaki
M
Jones
Phillip B
PB
Ay
Hakan
H
Boas
David A
DA
Moskowitz
Michael A
MA
Ayata
Cenk
C
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D051379:Mice; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use
D010108:Oxyhemoglobins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine