Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.
Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine.


CONCLUSIONS
In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.
Prielipp
R C
RC
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. prielipp@wfubmc.edu
Wall
M H
MH
Groban
L
L
Tobin
J R
JR
Fahey
F H
FH
Harkness
B A
BA
Stump
D A
DA
James
R L
RL
Cannon
M A
MA
Bennett
J
J
Butterworth
J
J
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003864:Depression, Chemical; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D018818:Fenoldopam / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D014055:Tomography, Emission-Computed; D017585:Ultrasonography, Doppler, Transcranial
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D018341:Receptors, Adrenergic, alpha-2; D017447:Receptors, Dopamine D1; D018818:Fenoldopam