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CrossTalk proposal: The middle cerebral artery diameter does change during alterations in arterial blood gases and blood pressure

2016; Wiley; Volume: 594; Issue: 15 Linguagem: Inglês

10.1113/jp271981

1469-7793

Ryan L. Hoiland, Philip N. Ainslie,

Cerebrovascular and Carotid Artery Diseases

Since the introduction of transcranial Doppler (TCD) ultrasound (Aaslid et al. 1982), the ostensible constancy of middle cerebral artery (MCA) diameter during changes in arterial blood gases and/or arterial blood pressure (ABP) has remained controversial (Kontos, 1989; Giller, 2003; Ainslie & Hoiland, 2014). Due to its ease of use, high temporal resolution, and non-invasive nature, TCD has significantly shaped the current understanding of human cerebrovascular physiology. However, TCD has always been tainted by the major assumption of an unchanged MCA diameter; that is, changes in MCA velocity (MCAv) are thought to accurately reflect changes in cerebral blood flow (CBF). Early on, the assumption of MCA constancy was largely speculative and inferred from indirect observations such as correlation of MCAv with various flow parameters (e.g. extra-cranial flow through the internal carotid artery (ICA); Bishop et al. 1986; van der Linden et al. 1991; Newell et al. 1994; Hatab et al. 1997). For example, the study by Newell and colleagues showed a strong correlation (r = 0.99) between MCAv and ICA flow, but studied anaesthetized subjects and correlated mean not individual data; the approach of 'forcing' a regression through mean data is known to artificially inflate correlational values. One must also consider that at rest ∼30% of ICA flow is distributed to the anterior cerebral artery (Zarrinkoob et al. 2015), and the assumption of unity between ICA flow and MCAv is further contingent on a constant distributive relationship between the middle and anterior cerebral arteries during alterations in arterial blood gases and ABP. Strength of the Doppler power signal has also been used to indicate MCA diameter constancy during hypercapnia (Poulin & Robbins, 1996), hypoxia (Poulin & Robbins, 1996) and hypotension (Newell et al. 1994). Yet, Doppler power has in a contradictory fashion been accepted as an indicator of MCA constancy when in agreement with experimental hypotheses (Poulin et al. 1996, 1998) but disregarded when in disagreement with experimental hypotheses (Poulin et al. 1999). The speculative nature of this technique is likely to be due to its lack of experimental validation. In this respect, early use of TCD was coupled to a 'faith' that MCA diameter was constant. More recently, high resolution duplex ultrasound measurement of CBF through extra-cranial cerebral arteries (i.e. ICA and vertebral artery) and automated wall tracking software have been utilized to complement MCAv measures during both reductions (Liu et al. 2013; Lewis et al. 2015) and elevations in ABP (Liu et al. 2013). These studies, and others (Valdueza et al. 1999), have demonstrated, in contrast to previous studies (e.g. Newell et al. 1994), that the MCAv and ICA flow responses differ during changes in ABP. While ICA velocity and MCAv changes do not differ during hypotension, it is the constriction (∼5%) of the ICA that results in the difference between ICA flow and MCAv (Lewis et al. 2015). This discrepancy highlights the limitations and uncertainties of drawing conclusions on MCA diameter from indirect measurements. Early angiographic studies provided preliminary evidence for CO2 driven changes in MCA diameter (Huber & Handa, 1967; Du Boulay & Symon, 1971). Then, Giller and colleagues directly measured the diameter of the MCA M1 segment during craniotomy (Giller et al. 1993). Albeit a crude assessment of MCA diameter they observed an approximate 2% change in diameter over a 10 mmHg range of the partial pressure of arterial CO2 () and a 2.5% change over an 18 mmHg range of ABP. Due to the minimal (yet significant relative to impact on flow) changes in MCA diameter, this study has been cited as support for (Newell et al. 1994), and evidence against (Willie et al. 2012) the constancy of MCA diameter. For the manipulation of , the 'confirmation of faith' for MCA constancy and thus 'validation' of TCD was provided using a 1.5 T magnetic resonance imaging (MRI) on healthy, conscious, and unanaesthetized humans, which displayed constancy of MCA diameter during hypercapnia (Serrador et al. 2000). This study superseded previous imaging work confounded by anaesthesia and co-morbidities (Huber & Handa, 1967; Djurberg et al. 1998) and has majorly impacted the study of cerebrovascular physiology with >380 citations in the last 15 years (Web of Science, Thomas Reuters). Unfortunately, this study suffered from a small sample size (n = 6) and, more importantly, poor MRI resolution. For example, the pixel size was equal to ∼20% of average MCA diameter, which rendered it incapable of detecting small yet significant changes in MCA diameter (Serrador et al. 2000). These limitations were also present during MRI assessment of MCA diameter during hypocapnia (Valdueza et al. 1997). Recently, higher resolution MRI (3 and 7 T) has shown both dilatation and constriction of the MCA during hyper- and hypocapnia, respectively (Verbree et al. 2014; Coverdale et al. 2014, 2015). They have also highlighted that MCA diameter may remain unchanged during small changes in (i.e. ±5 mmHg from baseline), although no definitive threshold for MCA vasomotion has been characterized. During reductions in the partial pressure of arterial oxygen, transcranial colour coded Doppler US (an ultrasound approach that, unlike TCD, allows estimation of MCA diameter) has demonstrated dilatation of the MCA during both normobaric (Wilson et al. 2011; Imray et al. 2014) and hypobaric (Wilson et al. 2011; Willie et al. 2014) hypoxia. These results have been verified at sea level by 3 T MRI (Wilson et al. 2011) providing convincing data that the MCA dilates in hypoxia. Given the above-presented arguments, it is apparent that the technically superior and direct studies of MCA diameter refute the assumption of MCA diameter constancy during alterations in arterial blood gases (e.g. Wilson et al. 2011; Verbree et al. 2014; Coverdale et al. 2014). While there has been no direct assessment of MCA diameter using high resolution imaging techniques (e.g. MRI) during alterations in ABP, high resolution ultrasound assessment of the ICA has exemplified discordant ICA flow compared with MCAv, which may indicate a lack of MCA diameter constancy (Liu et al. 2013; Lewis et al. 2015). Currently, the only direct assessment of MCA diameter during alterations in ABP has reported changes in MCA diameter (Giller et al. 1993). Until MCA diameter changes have been explicitly determined for a specific experimental paradigm, MCAv cannot be assumed to accurately represent changes in CBF. Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief (250 word) comment. Comments may be submitted up to 6 weeks after publication of the article, at which point the discussion will close and the CrossTalk authors will be invited to submit a 'Last Word'. Please email your comment, including a title and a declaration of interest, to jphysiol@physoc.org. Comments will be moderated and accepted comments will be published online only as 'supporting information' to the original debate articles once discussion has closed. Ryan Hoiland is a PhD student at the University of British Columbia – Okanagan. His research focus is on the mechanisms regulating cerebral blood flow during alterations in arterial blood gases in humans. Philip Ainslie is currently a Professor in the School of Health and Exercise Sciences at the University of British Columbia – Okanagan and holds a Canada Research Chair in Cerebrovascular Physiology. His main research focus is on the fundamental mechanisms that regulate human cerebral blood flow in health and in disease. He has a particular interest in how environmental stress – especially in the context of hypoxia, temperature, pressure and exercise – may impact on cerebral blood flow regulation. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. The authors declare no conflict of interest, financial or otherwise. Both authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. This work was supported by a Canadian Research Chair in cerebrovascular physiology held by P.N.A.; R.L.H. was supported by a NSERC postgraduate doctoral scholarship. We would like to thank Anthony Bain for feedback on the article.