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, fen oldopam, is a potent systemic vasodilator with moderate alpha (2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation ar e undefined. We therefore hypothesized that infusion of fenoldopam would de crease mean arterial blood pressure (MAP) and might concurrently decrease C BF via vascular alpha (2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomogr aphy to measure CBF in multiple cortical and subcortical regions of interes t. In addition, bioimpedance cardiac output and middle cerebral artery bloo d flow velocity were determined during fenoldopam-induced hypotension. Thre e men and four women, aged 25-43 yr, completed the study. Fenoldopam infuse d at 1.3 +/- 0.4 mug. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from ba seline: 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 decre ased 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 fenol dopam, with or without concurrent phenylephrine.