Response to Letter by Tzeng et al
We thank Tzeng et al for their very interesting comments on the new evidence for interactions between cerebrovascular autoregulation (CA) and the arterial baroreflex system. As stated by the authors, studies focusing on this association are only emerging, thus the evidence is rather limited at this time. Nevertheless, we agree on the hypothesis that the autonomic nervous system, including the baroreflex, plays an important role in regulating cerebral blood flow (CBF), presumably also integrating changes in the dynamic CA.1–3
Tzeng et al report a positive correlation between baroreflex sensitivity (BRS) and arterial blood pressure variability. This is in line with our observation that decreased BRS was associated with increased blood pressure variability in stroke patients, possibly contributing to the occurrence of hypertensive crises in the acute phase (M. Sykora, et al, unpublished data, 2010).4 They suggest an inverse correlation between dynamic CA and BRS, implicating possible adjustment of the dynamic CA for the demands of altered BRS with increased blood pressure variability. Interestingly, we have observed a possibly related, albeit opposite, phenomenon examining BRS in neurocritical care patients experiencing raised intracranial pressure (ICP). In patients with ICP levels impairing the functioning of dynamic CA, we found baroreflex hypersensitivity followed by blood pressure elevations, putatively targeting the restoration of normal CBF (M. Sykora, et al, unpublished data, 2010). The BRS correlated strongly and positively with ICP levels. Increased ICP has been shown to shift upward the lower limit of CBF autoregulation, implicating that the compensation for an acute increase in ICP with an equal increase in arterial blood pressure may not be sufficient to keep the CBF constant.5 We suggest that under these circumstances, the baroreflex system resets its sensitivity to compensate for the impaired CA. This consideration would be in line with the observations mentioned by Tzeng et al on inverse correlation between BRS and CA. Our finding may further support the “cross-linked” hypothesis that CA and BRS (autonomic drive) are a part of the same regulatory continuum.6
The pathophysiological reaction of raised ICP followed by hypertension and heart rate decline is clinically known as the Cushing reflex. It is thought to be a preterminal phenomenon accompanying cerebral lesions with mass effect. Indeed, this reflex becomes clinically manifest only at very high ICP levels. However, we observed baroreflex hypersensitivity, which may be considered as the mechanisms behind the Cushing response, also in patients with moderately elevated ICP with no clinical signs of hypertension and bradycardia (M. Sykora, et al, unpublished data, 2010). Here again, we hypothesize an underlying shift in the BRS, serving to adjust the CBF for states of altered CA or raised ICP. This implicates that the intracranial component of the baroreflex system may be regarded as a neuroprotective mechanism.
Thus, the interplay between arterial baroreflex and CA seems to have a crucial role in CBF regulation under normal and pathological conditions. However, the complex relationship between BRS and CA and its clinical implications remain to be elucidated more in detail in future studies.
Zhang R, Zuckerman JH, Iwasaki K, Wilson TE, Crandall CG, Levine BD. Autonomic neural control of dynamic cerebral autoregulation in humans. Circulation. 2002; 106: 1814–1820.
Ogoh S, Brothers RM, Eubank WL, Raven PB. Autonomic neural control of the cerebral vasculature: acute hypotension. Stroke. 2008; 39: 1979–1987.
Sykora M, Diedler J, Turcani P, Hacke W, Steiner T. Baroreflex: a new therapeutic target in human stroke? Stroke. 2009; 40: e678–e682.