The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjects exposed to endotoxemia.
Prospective descriptive study.
Hospital research laboratory.
Ten healthy young subjects (age: 32 ± 8 yrs [mean ± SD]; weight: 84 ± 10 kg; weight: 184 ± 5 cm; body mass index: 25 ± 2 kg/m2) participated in the study.
Systemic hemodynamics, middle cerebral artery mean flow velocity, and dynamic cerebral autoregulation evaluated by transfer function analysis in the very low (<0.07 Hz), low (0.07–0.15 Hz), and high (>0.15 Hz) frequency ranges were monitored in these volunteers before and after an endotoxin bolus (2 ng/kg; Escherichia coli).
Endotoxin increased body temperature of the subjects from 36.8 ± 0.4°C to 38.6 ± 0.5°C (p < .001) and plasma tumor necrosis factor-α from 5.6 (2.8–6.7) pg/mL to 392 (128–2258) pg/mL (p < .02). Endotoxemia had no influence on mean arterial pressure (95 [74–103] mm Hg vs. 92 [78–104] mm Hg; p = .75), but increased cardiac output (8.3 [6.1–9.5] L·min–1 vs. 6.0 [4.5–8.2] L·min–1; p = .02) through an elevation in heart rate (82 ± 9 beats·min–1 vs. 63 ± 10 beats·min–1; p < .001), whereas arterial carbon dioxide tension (37 ± 5 mm Hg vs. 41 ± 2 mm Hg; p < .05) and middle cerebral artery mean flow velocity (37 ± 9 cm·sec–1 vs. 47 ± 10 cm·sec–1; p < .01) were reduced. In regard to dynamic cerebral autoregulation, endotoxemia was associated with lower middle cerebral artery mean flow velocity variability (1.0 ± 1.0 [cm·sec–1] Hz–1 vs. 2.8 ± 1.5 [cm·sec–1] Hz–1; p < .001), reduced gain (0.52 ± 0.11 cm·sec–1.mm Hg–1 vs. 0.74 ± 0.17 cm·sec–1.mm Hg–1; p < .05), normalized gain (0.22 ± 0.05 vs. 0.40 ± 0.17%·%–1; p < .05), and higher mean arterial pressure-to-middle cerebral artery mean flow velocity phase difference (p < .05) in the low frequency range (0.07–0.15 Hz).
These data support that the reduction in arterial carbon dioxide tension explains the improved dynamic cerebral autoregulation and the reduced cerebral perfusion encountered in healthy subjects during endotoxemia.
From the Division of Kinesiology (PB), Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Québec, Canada; the Department of Internal Medicine (Y-SK, JvL) and the Laboratory for Clinical Cardiovascular Physiology (Y-SK, JvL), Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; the Department of Anesthesia (NHS), The Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; the Department of Cardiology (JBR), Gentofte University Hospital, Gentofte, Denmark; and the School of Biomedical Sciences (JvL), University of Nottingham Medical School, Queen’s Medical Centre, Nottingham, U.K.
*See also p. 1986.
Novo Nordisk sponsored this study.
This work was performed at the Department of Anesthesia, The Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Dr. Secher received funding from Copenhagen University. The remaining authors have not disclosed any potential conflict of interest.
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