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Sympathetic activity and cerebral oxygenation
- Patrice Brassard, Thomas Seifert, Niels H. Secher (1 September 2009)
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Norepinephrine and cerebral blood flow
- Iain K Moppett (16 July 2009)
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Patrice Brassard Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark, Thomas Seifert, Niels H. Secher
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Dear Sir, We thank Dr Moppett (1) for his interest in the potential influence of the sympathetic nervous system in the regulation of cerebral blood flow (CBF). We can only agree with Dr Moppett that the arterial carbon dioxide tension (PaCO2) has a powerful influence on CBF although, in situations with a reduced cardiac output as during standing, the reduction in cerebral perfusion does not seem to be explained by the concomitant reduction in PaCO2 (2). More likely, the orthostatic decrease in cerebral perfusion is a reflection of a sympathetic restrain on CBF induced by the reduction in cardiac output (3). Yet, it remains controversial whether sympathetic activation influences CBF. There is biochemical evidence suggesting that sympathetic activity does influence CBF in humans (4). However, there are also good reasons to explain the relatively smaller influence of sympathetic activity on CBF in comparison with its influence on many other regions of the circulation. As demonstrated for skeletal muscles, flow is a balance between the metabolic demand of the tissue and sympathetic activity (5). It may be that the high metabolic rate of the brain, present even at rest, provides for a metabolic milieu favouring vasodilatation, which in turn is counteracting the normal ability of sympathetic nerves, when stimulated, to cause vasoconstriction and a reduction in CBF. In fact, the question is not whether the sympathetic nervous system influences CBF or not, but under which circumstances. In our study (6), the question is whether sympathetic innervation of the cerebral vasculature makes it sensitive to pharmacologic activation by alpha-receptors. In this study (6), norepinephrine was infused to spontaneously breathing healthy subjects. Most likely because of an influence of norepinephrine on the chemoreceptors, ventilation increased as demonstrated by a small reduction in PaCO2. To circumvent that confounding factor, we have administered phenylephrine to anaesthesized patients while they were under controlled ventilation. Similarly to what we have reported for healthy subjects following administration of norepinephrine, these patients demonstrated a 14 % reduction in frontal lobe oxygenation measured by near-infrared spectroscopy during administration of phenylephrine. Although we admit that this reduction in cerebral oxygenation reported following the infusion of norepinephrine in healthy subjects may have been, at least potentially, influenced by a lowering in PaCO2, the patients related observations indicate that PaCO2 is not the sole explanation for a decrease in cerebral oxygenation during administration of alpha-adrenergic drugs. References 1) Moppett IK. Norepinephrine and cerebral blood flow. Br J Anaesth (electronic e-letter), 2009. 2) Immink RV, Truijen J, Secher NH and Van Lieshout JJ. Transient influence of end-tidal carbondioxide tension on the postural restrain on cerebral perfusion. J Appl Physiol in press 2009. 3) Van Lieshout JJ, Wieling W, Karemaker JM and Secher NH. Syncope, cerebral perfusion and oxygenation (invited review). J Appl Physiol 94: 833-848, 2003. 4) Michell DA, Lambert G, Secher NH, Raven PB, Van Lieshout JJ and Esler MD. Jugular venous overflow of noradrenaline and noradrenaline metabolites from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans. J Physiol 587: 2589-2597, 2009. 5) Secher NH and Volianitis S. Are the arms and legs in competition for cardiac output? (invited review) Med Sci Sports Exerc 38: 1797-1803, 2006. 6) Brassard P, Seifert T and Secher NH. Is cerebral oxygenation negatively affected by infusion of noradrenaline in healthy subjects? Br J Anaesth 102: 800-805, 2009. Conflict of Interest:None declared |
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Iain K Moppett University of Nottingham
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To the editor Dear Sir, We read with interest the study by Brassard and colleagues (1) regarding the effects of increasing doses of norepinephrine on cerebral haemodynamics and oxygenation. We congratulate them for a very well executed and reported study. The study is interesting for a number of reasons. First, unlike previous investigators (2-4), Brassard and colleagues found a decrease in middle cerebral artery flow velocity (MCA FV) with doses of norepinephrine sufficient to increase mean arterial pressure by around 25%. As acknowledged by the authors, studies describing increases in MCA FV under anaesthesia may be confounded by the effects of the anaesthetic agents themselves. However, studies in healthy volunteers (2- 4) and patients with migraine (3) have all failed to demonstrate reductions in MCA FV. Of particular relevance are the studies from Poulin's group (5), which, using a normopcapnic hyperventilation technique with a constant PaCO2, demonstrated no change in MCA FV with physiological sympathetic stimulation. Although Brassard's results are at odds with previous data, it is of course possible that the meticulous technique employed in the reported study allowed very small changes in MCA FV to be detected. The authors rightly point to three different forms of measurement in this study which support their conclusions that cerebral blood flow is reduced by norepinephrine. However, we suggest that norepinephrine is only an indirect cause. As Brassard and colleagues point out, there were small changes in PaCO2 during norepinephrine infusion. Typical values of cerebral carbon dioxide reactivity are of the order of 15 – 20 % / kPa (6). A reduction in PaCO2 would therefore be expected to cause a reduction in CBF of around 3 – 4%. This is entirely consistent with the data presented and the effects on SjO2 have been predicted by computational modelling (7). Brassard and colleagues acknowledge this in the paper, but go on to conclude that norepinephrine negatively affects cerebral oxygenation. The explanation of the results does not require new theories regarding the effects of norepinephrine on autoregulation. We suggest that norepinephrine does not affect cerebral autoregulation in healthy volunteers but the associated reduction in PaCO2 causes small but measurable falls in cerebral blood flow. Oxygen extraction increases and therefore SjO2 falls. 1) Brassard P, Seifert T, Secher NH. Is cerebral oxygenation negatively affected by infusion of norepi-nephrine in healthy subjects? Br J Anaesth 2009;102:800-5 2) Moppett IK, Sherman R, Wild MJ, Latter JA, Mahajan RP. Effects of norepinephrine and glyceryl trinitrate on cerebral haemodynamics: transcranial Doppler study in healthy volunteers. Br J Anaesth 2008;100:240-4 3) Lindholt M, Petersen KA, Tvedskov JF, Iversen HK, Olesen J, Tfelt -Hansen P. Lack of effect of norepinephrine on cranial haemodynamics and headache in healthy volunteers. Cephalalgia 2009; 29:384-38 4) Kimmerly DS, Tutungi E, Wilson TD, et al. Circulating norepinephrine and cerebrovascular control in conscious humans. Clin Physiol Func Imaging. 2003;23:314-9 5) Ainslie PN, Ashmead JC, Ide K, Morgan BJ, Poulin MJ. Differential responses to CO2 and sympathetic stimulation in the cerebral and femoral circulations in humans. J Physiol 2005;566:613-24 6) Relationship between middle cerebral artery blood velocity and end -tidal PCO2 in the hypocapnic-hypercapnic range in humans. Ide K, Eliasziw M, Poulin MJ. J Appl Physiol 2003;95;129-37 7) Moppett IK, Hardman JG. Modelling the causes of variation in brain tissue oxygenation. Anesth Analg 2007;105:1104-12. Conflict of Interest:None declared |
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