Phenylephrine ameliorates cerebral cytotoxic edema and reduces cerebral infarction volume in a rat model of complete unilateral carotid artery occlusion with severe hypotension.
BACKGROUND
Phenylephrine is a selective alpha(1) adrenergic receptor agonist that increases arterial blood pressure by peripheral vasoconstriction. However, whether phenylephrine improves the outcome of cerebral ischemia in patients with internal carotid artery disease during hemorrhagic shock is unclear.


METHODS
(Experiment 1) Twenty-one adult male Sprague-Dawley rats were anesthetized with isoflurane and their lungs mechanically ventilated. After the right common carotid artery was ligated, arterial blood was withdrawn until mean arterial blood pressure (MAP) reached 30 mm Hg to induce cerebral ischemia. After MAP was maintained at 30 mm Hg for 10 min, the animals were randomly allocated to three groups (n = 7 each). In the phenylephrine group, phenylephrine was administered IV to maintain a MAP of 70 +/- 3 mm Hg for 5 min. In the saline group, an identical volume of normal physiologic saline was continuously administered for 5 min. In the control group, neither phenylephrine nor saline was administered and MAP was maintained at 30 mm Hg. At 30 min of exsanguination, the withdrawn blood was reinfused IV at a rate of 0.25 mL/min. Diffusion-weighted magnetic resonance images were serially acquired and apparent diffusion coefficient maps were created to determine the volume of cytotoxic edema. (Experiment 2) To analyze the effect of phenylephrine on the regional cerebral blood flow (rCBF) in the right middle cerebral artery territory, rCBF was measured using laser Doppler flowmetry in 15 additional rats (n = 5 each).


RESULTS
(Experiment 1) At 10 min of exsanguination, there were no significant differences in the volume of cytotoxic edema among the phenylephrine (357.5 +/- 93.5 mm(3)), saline (333.5 +/- 69.6 mm(3)), and control (303.1 +/- 85.8 mm(3)) groups. Low apparent diffusion coefficient regions significantly expanded with time in the control group, whereas they started to decrease just after phenylephrine infusion and almost all had disappeared within 30 min in the phenylephrine group. The final infarction volume in the phenylephrine group (3.9 +/- 2.6 mm(3), P < 0.01) was significantly lower than that in the saline group (341.5 +/- 213.7 mm(3)) and control group (509.1 +/- 197.0 mm(3)). (Experiment 2) Although rCBF decreased to 40%-50% of the baseline at 10 min of exsanguination, phenylephrine immediately increased rCBF over the baseline level. In the saline group, rCBF increased significantly, but there was some delay compared with the phenylephrine group.


CONCLUSIONS
Phenylephrine ameliorated cytotoxic edema and decreased the infarction volume in a rat model of complete unilateral carotid artery occlusion with severe hypotension. These findings suggest that phenylephrine transiently increased CBF without increasing the tonus of cerebral vasculature during hemorrhagic shock.
Ishikawa
Seiji
S
Department of Anesthesiology, Tokyo Medical and Dental University, Graduate School of Medicine, Tokyo, Japan. ishikawa.mane@tmd.ac.j
Ito
Hiroyuki
H
Yokoyama
Kuninori
K
Makita
Koshi
K
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016893:Carotid Stenosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D008297:Male; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D010656:Phenylephrine