Reduced Regional and Global Cerebral Blood Flow During Fenoldopam-Induced Hypotension in Volunteers

• Published in: Anesthesia and analgesia Vol. 93; no. 1; pp. 45 - 52
• Main Authors: Prielipp, Richard C., Wall, Michael H., Groban, Leanne, Tobin, Joseph R., Fahey, Frederic H., Harkness, Beth A., Stump, David A., James, Robert L., Cannon, Mark A., Bennett, Judy, Butterworth, John
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.07.2001; Lippincott
• Subjects: Adolescent; Adult; Antihypertensive Agents - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Brain - diagnostic imaging; Cardiac Output - drug effects; Cardiovascular system; Cerebrovascular Circulation - drug effects; Depression, Chemical; Dopamine Agonists - pharmacology; Female; Fenoldopam - pharmacology; Heart Rate - drug effects; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Dopamine D1 - drug effects; Tomography, Emission-Computed; Ultrasonography, Doppler, Transcranial; Vasodilator agents. Cerebral vasodilators; Human; Induced arterial hypotension; α2-Adrenergic receptor; Agonist; Vasodilator agent; Healthy subject; D1 Dopamine receptor; Central nervous system; Hemodynamics; Blood flow; Brain (vertebrata); Fenoldopam
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-200107000-00011

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 α2-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 α2-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 μg · kg−1 · min−1 (mean ± sd) reduced MAP 16% from baselinefrom 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.