Elsevier

Medical Engineering & Physics

Volume 36, Issue 11, November 2014, Pages 1487-1495
Medical Engineering & Physics

Static autoregulation in humans: a review and reanalysis

https://doi.org/10.1016/j.medengphy.2014.08.001Get rights and content

Abstract

Introduction

Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF.

Methods

The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n = 28); therefore, CBF was also adjusted to account for small changes in PaCO2.

Results

The linear regression coefficient between MAP and CBF (or velocity) of 0.82 ± 0.77%ΔCBF/%ΔMAP during decreases in MAP (n = 23 experiments) was significantly different than the relationship of 0.21 ± 0.47%ΔCBF/%ΔMAP during increases (n = 26 experiments; p < 0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64 ± 1.16%ΔCBF/%ΔMAP (n = 16) and 0.39 ± 0.30%ΔCBF/%ΔMAP (n = 12) for increased vs. decreased MAP changes, respectively (p = 0.60).

Conclusion

The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2.

Introduction

Cerebral autoregulation (CA) is a theoretical construct characterized by the changes in cerebral blood flow (CBF) during changes in blood pressure (BP), in which physiological mechanisms attempt to maintain constancy of CBF. Although the physiological underpinnings remain obscure [1], CA is characterized on a continuum ranging from static (steady-state) to dynamic (transient) components. Static CA is typically described as operating over several minutes to hours and represents the steady-state relationship between mean arterial pressure (MAP) and CBF [2]. In contrast, dynamic CA commonly refers to the cerebral pressure–flow relationship as observed during transient changes in MAP (e.g., with changes in posture), taking place over a period of seconds [3], [4]. Although these two metrics act on a continuum, the cerebrovasculature appears to be better suited at buffering lower frequency fluctuations in BP (<0.20 Hz), than higher frequency fluctuations (>0.20 Hz) [5]. The current study focuses on the cerebral pressure–flow relationship that is associated with static CA.

Many studies have been performed to evaluate CA in healthy subjects and patients with perturbations of MAP while measuring concordant changes in CBF. The first key paper to address this topic was the published review by Lassen in 1959 describing the notion that CBF remains constant for MAP values between 60 and 150 mmHg [6]. This so-called ‘static’ CA curve was notably formulated from 7 different studies with 11 different subject groups. The subject groups’ CBF was measured at a single MAP value and were not observed throughout a range in MAP. Furthermore, these subjects either had a pathological condition and/or were taking pharmaceuticals. This classic report has been commonly (mis)-cited as depicting a mean curve for intra-subject CA relationships collected over a range of MAP values versus actually representing connected individual inter-subject data points. Indeed, fixing a line through several singular subject MAP/CBF relationships ignores the potential of chronic resetting, e.g., in the case with sustained hypertension [7]. Upon closer examination of the response for CBF (or a related index of CBF) to a change in MAP, recent studies have revealed that this relationship appears to be more pressure passive [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22] than previously described. However, the limitations to drawing inferences from the majority of recent studies are three-fold. First, transcranial Doppler ultrasound (TCD) has been widely used to evaluate CBF velocity (CBFV) [8], [9], [10], [11], [18], [20], [21], [22], which accurately represents CBF exclusively in the event that diameter of the insonated vessel remains constant. Whether this is the case with severe decreases or increases in MAP is unclear [23], [24]. Second, many of these studies have also investigated CA through the use of cardiovascular-active substances [10], [11], [14], [17], [20], [22], which may have had an influence on cerebrovascular tone. Finally, only one of the previously mentioned studies corrected for effects of the partial pressure of arterial carbon dioxide (PaCO2) [12] on CBF. This is critically important since PaCO2—via changes in alveolar ventilation—can be profoundly altered during changes in blood pressure. It is well established that CBF is highly sensitive to changes in PaCO2, yielding an approximate 4 and 2% change in flow per mmHg change in PaCO2 above and below eupneic PaCO2, respectively [25].

The aim of this study was to conduct a literature analysis to provide an up-to-date understanding of the static relationship between MAP and CBF. Specifically, we formulated a new comprehensive cerebral pressure–flow response curve based on results from an extensive review of studies in which MAP was decreased and/or increased within each subject group. Although the mechanisms are not entirely understood, there is evidence in both humans [26], [27], [28] and animals [29] that support the idea of hysteresis in the relationship between MAP and CBF. That is, the cerebrovasculature is better able to buffer against increases, as opposed to decreases in MAP. As such, we compared the separate CBF response to increases and decreases in MAP.

Section snippets

Methods

Pubmed and Scopus were searched (Oct.–Dec. 2012) for studies with the terms ‘cerebral blood flow’, ‘arterial pressure’, and ‘healthy subjects’, having been published between 1960 and 2012. Non-human experiments and non-English studies were excluded. The initial review resulted in a total of 459 studies. The selected population was healthy subjects between 18 and 65 years of age. Within studies that had both clinical patients and control subjects, the results of the control subjects were

Results

From all reviewed articles, 40 were included in this study. Multiple within study or single study experiments were divided into categories of decreasing MAP (n = 23) and increasing MAP (n = 26); individual study results are depicted in Table 1, Table 2. In the studies where MAP was decreased, the calculated slopes were between −0.39 and 3.46%ΔCBF/%ΔMAP. The average slope for decreased MAP was 0.82 ± 0.77%ΔCBF/%ΔMAP (Fig. 2; or 0.97 ± 0.91%ΔCBF/mmHg MAP). In the studies where MAP was increased, the

Discussion

The results of this review indicate that during static changes in MAP, without an applied correction factor for CO2, the cerebral vasculature possesses more efficient autoregulation during increases in MAP as opposed to decreases. This apparent hysteresis is lost following a global correction for PaCO2. The findings of this analysis are discussed, the potential limitations of experimental approaches are highlighted, and future directions are considered.

Relationship between MAP and CBF: The

Perspective

Our findings provide new insights into the steady-state cerebral pressure–flow response for healthy subjects, although it is important to further confirm this newly depicted relationship in future studies. A definitive, within-subjects assessment of global and regional CBF across a range of non-pharmacologically and pharmacologically perturbed BP with maintained PaCO2 has yet to be completed. Until this is done, we cannot define what constitutes ‘normal’ and ‘impaired’ static CA.

Conclusion

In conclusion, we interpret our findings to highlight that the cerebral vasculature may have more efficient autoregulatory ability in the face of increased MAP, versus that during decreases in MAP. The apparent loss of this relationship following our attempt at correcting for changes in PaCO2 highlights the need for future, unified, research. However, we hypothesize that future studies involving properly controlled PaCO2 values will display an autoregulatory hysteresis in agreement with our

Funding

None.

Ethical approval

Not required.

Conflict of interest

None declared.

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