Cerebral vasoconstriction in response to hypocapnia is maintained after ischemia/reperfusion injury in newborn pigs.
OBJECTIVE
Hypocapnic cerebral vasoconstriction is used therapeutically to reduce elevated intracranial pressure caused by cerebral edema. Because cerebral ischemia/reperfusion injury causes a selective loss of prostanoid-dependent responses, including vasodilation to hypercapnia, we designed these experiments to examine the effect of ischemia/reperfusion on hypocapnic cerebral vasoconstriction.


METHODS
Microvascular responses were studied in 10 newborn pigs (closed cranial window) in response to hyperventilation-induced hypocapnia (PaCO2, 22 +/- 2 mm Hg) both before and 45 minutes after 20 minutes of global cerebral ischemia. Responses to hypercapnia (PaCO2, 63 +/- 3 mm Hg), topical isoproterenol (10(-7) M), and norepinephrine (10(-4) M) were also studied before and after ischemia in the same animals for comparison.


RESULTS
Before ischemia/reperfusion, pial arterioles vasoconstricted to hypocapnia (-17 +/- 2%) and norepinephrine (-35 +/- 4%) and vasodilated to CO2 (37 +/- 7%) and isoproterenol (25 +/- 2%). After ischemia/reperfusion, the constriction of pial arterioles to hypocapnia (-19 +/- 2%) was similar to that before ischemia. This is in contrast to the loss of dilation to hypercapnia. Dilation to isoproterenol and constriction to norepinephrine were not affected by ischemia.


CONCLUSIONS
Hypocapnic cerebral vasoconstriction is maintained after ischemia/reperfusion. Since prostanoid-dependent responses, such as hypercapnic dilation, are lost following cerebral ischemia, these data suggest that hypocapnic constriction is not dependent on an intact prostanoid system and that cerebral vascular responses to CO2 involve multiple mechanisms, depending on whether CO2 is increasing or decreasing from baseline.
Mirro
R
R
Department of Pediatrics, University of Tennessee, Memphis 38163.
Lowery-Smith
L
L
Armstead
W M
WM
Shibata
M
M
Zuckerman
S L
SL
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D016857:Hypocapnia / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D015427:Reperfusion Injury / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction
D007545:Isoproterenol; D009638:Norepinephrine