Research Publication: New Study by Dr. Can Ozan Tan

New Study Finds Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation

DEPARTMENT MEMBER Can Ozan Tan, PhD, a researcher at the Spaulding Cardiovascular Lab, co-authored a study published in the June issue of Stroke, a journal of the American Heart Association. The study provided, for the first time, a comprehensive model of how brain blood flow is controlled.

Dr. Tan explained that “Annually in the U.S., over a million individuals suffer from acute cerebrovascular events, ranging from mild concussions to severe hemorrhage. Among the most serious sequelae of these events is the secondary neural injury due to cerebral vascular dysfunction. Prior work aimed at improving our understanding of human cerebrovascular regulation has explored individual physiological mechanisms in isolation, but none has attempted to consolidate the individual roles of these mechanisms into a comprehensive model of cerebral autoregulation, the overall cerebral pressure–flow relationship.”

Dr. Tan, with his team, retrospectively analyzed this relationship before and after pharmacological blockade of -adrenergic-, muscarinic-, and calcium channel-mediated mechanisms in 43 healthy volunteers to determine the relative contributions of the sympathetic, cholinergic, and myogenic controllers to cerebral autoregulation. Projection pursuit regression was used to assess the effect of pharmacological blockade on the cerebral pressure-flow relationship. Subsequently, ANCOVA decomposition was used to determine the cumulative effect of these 3 mechanisms on cerebral autoregulation and whether they can fully explain it.

Sympathetic, cholinergic, and myogenic mechanisms together accounted for 62% of the cerebral pressure-flow relationship (P<0.05), with significant and distinct contributions from each of the 3 effectors. ANCOVA decomposition demonstrated that myogenic effectors were the largest determinant of the cerebral pressure-flow relationship, but their effect was outside of the autoregulatory region where neurogenic control appeared prepotent.

The results suggest that myogenic effects occur outside the active region of autoregulation, whereas neurogenic influences are largely responsible for cerebral blood flow control within it. However, the model of cerebral autoregulation left 38% of the cerebral pressure-flow relationship unexplained, suggesting that there are other physiological mechanisms that contribute to cerebral autoregulation. These results have significant implications for treatment and rehabilitation of conditions that impact brain blood flow, ranging from traumatic brain injury and spinal cord injury to subarachnoid hemorrhage and stroke. 

The full study can be viewed in the June 2014 issue of Stroke (45:1771–1777).

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