Thesis defense Aisha vanden Abeelen (Donders Series 170)

3 December 2014

Promotors: Prof.dr. M.G.M. Olde Rikkert, Prof.dr. ir. C.H. Slump

Copromotors: Dr. J.A.H.R. Claassen, dr. ir. J. Lagro

In control. Methodological and clinical aspects of cerebral autoregulation and haemodynamics

The human brain depends highly on an adequate and stable supply of blood with oxygen and glucose. The most important aspects of the body’s perfusion regulation consist of the integrated control of systemic blood pressure and cerebral blood flow via the arterial baroreflex and cerebral autoregulation. The baroreflex is a reflex loop with cardiac, vascular and cerebral components involved in short-term blood pressure regulation . Changes in blood pressure lead to changes in the arterial vessel wall, which are sensed by the baroreceptors and information is sent to the brainstem. Via the autonomic nervous system heart rate and vascular tone are changed to restore the blood pressure. A clinical example is the drop in blood pressure upon standing, which the baroreflex corrects by a rapid increase in heart rate and vasoconstriction. Cerebral autoregulation acts to maintain a relatively constant cerebral blood flow despite fluctuations in blood pressure. Cerebral autoregulation is achieved by changes in cerebral vascular tone in response to changes in intravascular pressure: when the blood pressure decreases the radius of the cerebral vessels increases (vasodilation; increasing the cerebral blood flow) and when the blood pressure increases the radius decreases (vasoconstriction; decreasing the cerebral blood flow).

When these mechanisms fail, the blood flow of the brains will strongly depend on the blood pressure. For example, when a drop in blood pressure occurs, also the brain blood flow will drop, which is not without danger. When the brain blood flow is less than 50% of normal, it may be no longer meet the needs of the neurons and can cause brain damage. The proper functioning of the baroreflex and cerebral autoregulation is therefore of great importance. However, literature shows that different conditions, such as stroke, narrowing of the carotid artery, dementia and head trauma can affect these mechanisms leading to an increased risk of (secondary) brain damage in patients with these disorders.

Therefore, the ability to accurately quantify the quality of the perfusion regulation is of importance in clinical practice. Monitoring the quality of brain perfusion may be of benefit in the care of patients with brain injury, meningitis or stroke. But it may also be of importance for early detection of, for example, neurodegenerative diseases.

My Ph.D. research consists of two parts. The first part focusses on the quantification of the cerebral autoregulation functioning. In the second part, the emphasis is shifted to haemodynamics in clinical practice. We aim to investigate whether perfusion regulation is changed in different pathophysiological conditions, including patients with Alzheimer's disease, patients with hypertension and patients with sepsis.