Dopamine therapy promotes cerebral flow-metabolism coupling in preterm infants (original) (raw)

Abstract

Objective

Dopamine is widely used to maintain blood pressure in very preterm infants, but it may affect neurovascular regulation as it crosses the immature blood–brain barrier. We contrasted the relationship between cerebral perfusion and oxygen metabolism in preterm infants treated with dopamine because of hypotension with normotensive controls.

Design

Prospective observational study in a neonatal intensive care unit.

Methods

Cerebral metabolic rate of oxygen consumption (CMRO2) was determined via measurements of cerebral blood flow (CBF) and cerebral venous saturation (CSvO2) using near infrared spectroscopy. Twenty-six infants (median gestation 26 weeks) were studied at a median postnatal age of 17 h. Infants were categorised as control (n = 16) or dopamine-treated (DOPA, n = 10).

Results

No relationship was found between CBF and CMRO2 in the control group, while a strong positive correlation was found in the DOPA group (R 2 = 0.62, P = 0.01). Cerebral fractional oxygen extraction (CFOE) and CBF showed strong negative correlation in the control infants (R 2 = 0.65, P < 0.001), but not in the DOPA group. CSvO2 was lower at decreased CBF (R 2 = 0.56, P < 0.001) in the control infants, but not in the DOPA group.

Conclusions

Cerebral blood flow-metabolism coupling in the very preterm brain differs strikingly from that in the mature brain, where CBF is coupled to CMRO2. In the very preterm brain, variations of cerebral oxygen extraction, not CBF, sustain CMRO2. In contrast, preterm infants receiving dopamine exhibit flow-metabolism coupling similar to the mature brain. These findings suggest a previously unrecognised role for dopamine in the preterm brain in promoting flow-metabolism coupling.

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References

1. Laughon M, Bose C, Allred E, O’Shea TM, Van Marter LJ, Bednarek F, Leviton A (2007) Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics 119:273–280
   Article PubMed Google Scholar
2. Edvinsson L, Krause D (2002) Catecholamines. In: Edvinsson L, Krause D (eds) Cerebral blood flow and metabolism. Lippincott Williams & Wilkins, Philadelphia, pp 191–211
   Google Scholar
3. Kopin I (1978) Measuring turnover of neurotransmitters in human brain. In: Lipton AM, Dimacio A, Killam KF (eds) Psychopharmacology: a generation of progress. Raven Press, New York, p 936
   Google Scholar
4. Seri I, Tulassay T, Kiszel J, Sulyok E, Ertl T, Bodis J, Csomor S (1984) Effect of low-dose dopamine therapy on catecholamine values in cerebrospinal fluid in preterm neonates. J Pediatr 105:489–491
   Article PubMed CAS Google Scholar
5. Seri I, Rudas G, Bors Z, Kanyicska B, Tulassay T (1993) Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates. Pediatr Res 34:742–749
   Article PubMed CAS Google Scholar
6. Wong FY, Leung TS, Austin T, Wilkinson M, Meek JH, Wyatt JS, Walker AM (2008) Impaired autoregulation in preterm infants identified by using spatially resolved spectroscopy. Pediatrics 121:e604–e611
   Article PubMed Google Scholar
7. Busija DW, Heistad DD (1984) Factors involved in the physiological regulation of the cerebral circulation. Rev Physiol Biochem Pharmacol 101:161–211
   Article PubMed CAS Google Scholar
8. Munro MJ, Walker AM, Barfield CP (2004) Hypotensive extremely low birth weight infants have reduced cerebral blood flow. Pediatrics 114:1591–1596
   Article PubMed Google Scholar
9. Back SA, Gan X, Li Y, Rosenberg PA, Volpe JJ (1998) Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci 18:6241–6253
   PubMed CAS Google Scholar
10. Edwards AD, Wyatt JS, Richardson C, Delpy DT, Cope M, Reynolds EO (1988) Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. Lancet 2:770–771
    Article PubMed CAS Google Scholar
11. Duncan A, Meek JH, Clemence M, Elwell CE, Tyszczuk L, Cope M, Delpy DT (1995) Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys Med Biol 40:295–304
    Article PubMed CAS Google Scholar
12. Elwell C (1995) Measurement of cerebral blood flow using NIRS. A practical users guide to near infra red spectroscopy. Hamamatsu Photonics KK, Hamamatsu, pp 69–85
    Google Scholar
13. Wong FY, Barfield CP, Campbell L, Brodecky VA, Walker AM (2008) Validation of cerebral venous oxygenation measured using near-infrared spectroscopy and partial jugular venous occlusion in the newborn lamb. J Cereb Blood Flow Metab 28:74–80
    Article PubMed Google Scholar
14. Kissack CM, Garr R, Wardle SP, Weindling AM (2005) Cerebral fractional oxygen extraction is inversely correlated with oxygen delivery in the sick, newborn, preterm infant. J Cereb Blood Flow Metab 25:545–553
    Article PubMed Google Scholar
15. Lemmers PM, Toet MC, van Bel F (2008) Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics 121:142–147
    Article PubMed Google Scholar
16. Meek JH, Firbank M, Elwell CE, Atkinson J, Braddick O, Wyatt JS (1998) Regional hemodynamic responses to visual stimulation in awake infants. Pediatr Res 43:840–843
    Article PubMed CAS Google Scholar
17. Erberich SG, Panigrahy A, Friedlich P, Seri I, Nelson MD, Gilles F (2006) Somatosensory lateralization in the newborn brain. Neuroimage 29:155–161
    Article PubMed Google Scholar
18. Heekeren HR, Obrig H, Wenzel R, Eberle K, Ruben J, Villringer K, Kurth R, Villringer A (1997) Cerebral haemoglobin oxygenation during sustained visual stimulation—a near-infrared spectroscopy study. Philos Trans R Soc Lond B Biol Sci 352:743–750
    Article PubMed CAS Google Scholar
19. Krimer LS, Muly EC 3rd, Williams GV, Goldman-Rakic PS (1998) Dopaminergic regulation of cerebral cortical microcirculation. Nat Neurosci 1:286–289
    Article PubMed CAS Google Scholar
20. Iadecola C (1998) Neurogenic control of the cerebral microcirculation: is dopamine minding the store? Nat Neurosci 1:263–265
    Article PubMed CAS Google Scholar
21. Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5:347–360
    Article PubMed CAS Google Scholar
22. Skov L, Pryds O, Greisen G (1991) Estimating cerebral blood flow in newborn infants: comparison of near infrared spectroscopy and 133Xe clearance. Pediatr Res 30:570–573
    PubMed CAS Google Scholar
23. Yoxall CW, Weindling AM (1998) Measurement of cerebral oxygen consumption in the human neonate using near infrared spectroscopy: cerebral oxygen consumption increases with advancing gestational age. Pediatr Res 44:283–290
    Article PubMed CAS Google Scholar
24. Kulik T, Kusano Y, Aronhime S, Sandler AL, Winn HR (2008) Regulation of cerebral vasculature in normal and ischemic brain. Neuropharmacology 55:281–288
    Article PubMed CAS Google Scholar

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Acknowledgements

Dr. F. Y. Wong was supported by an Australian Postgraduate Award. Project support was provided by the National Health and Medical Research Council (NHMRC) of Australia.

Conflict of interest statement

The authors have no financial relationships relevant to this article to disclose.

Author information

Authors and Affiliations

1. Ritchie Centre for Baby Health Research, Monash University, Level 5, Monash Medical Centre, 246 Clayton Road, Clayton, VIC, 3168, Australia
   Flora Y. Wong, Charles P. Barfield, Rosemary S. C. Horne & Adrian M. Walker
2. Monash Newborn, Monash Medical Centre, Melbourne, VIC, 3168, Australia
   Flora Y. Wong

Authors

1. Flora Y. Wong
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2. Charles P. Barfield
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3. Rosemary S. C. Horne
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4. Adrian M. Walker
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Corresponding author

Correspondence toAdrian M. Walker.

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Wong, F.Y., Barfield, C.P., Horne, R.S.C. et al. Dopamine therapy promotes cerebral flow-metabolism coupling in preterm infants.Intensive Care Med 35, 1777–1782 (2009). https://doi.org/10.1007/s00134-009-1602-5

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• Received: 04 January 2009
• Accepted: 16 July 2009
• Published: 01 August 2009
• Issue Date: October 2009
• DOI: https://doi.org/10.1007/s00134-009-1602-5

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