Cerebral Autoregulation

Introduction: From Static to Dynamic

The human brain constitutes only 2% of the body weight, but receives 15% of cardiac output, accounts for almost 20% of the total oxygen consumption, and consumes approximately 25% of total body glucose utilization. The human brain is by far the most expensive organ in term of energy expenditure in the whole body. Maintenance and restoration of transmembrane resting potential dissipated by postsynaptic and action potential and neurotransmitters recycling represent the main energetic cost at the brain. In addition, the brain has very limited energy storage and relies on coincidental increase of cerebral blood flow to comply the local brain activity. Mammalian brain is characterized by high metabolic activity with fine regulatory mechanisms, defined as cerebral autoregulation, to ensure adequate energy substrates supply in register with neuronal activity. Cerebral autoregulation enables the cerebral blood flow to remain relatively constant during variations of arterial pressure. It is critical for normal brain function, given the high metabolic demand and low energy reserve of the brain tissue.

The term autoregulation for the cerebral circulation was first introduced by Lassen in 1959. Before then, it was generally believed that the cerebral perfusion passively followed the changes of arterial blood pressure and that the cerebral vasculature did not possess any significant capacity for intrinsic control of the vascular tone. Lassen summarized the previous quantitative studies and concluded that the cerebral blood flow is independent of the changes of mean arterial blood pressure within a wide range of mean arterial blood pressure. He further suggested that the autoregulation was governed by the metabolic demands of the cerebral tissues .

It is important to note that the earlier studies of cerebral autoregulation relied on pharmacological interventions to establish a sustained period of hypotension and hypertension and, thus, described the response of cerebral blood flow, averaged over a longer period of time, to long-term changes in blood pressure with gradual onset. By plotting these changes in cerebral and mean arterial blood pressure, it was found that cerebral blood flow remains constant over a wide range of mean arterial blood pressure, defined as the plateau phase. In normotensive adults, the lower and upper arterial blood pressure limits of the cerebral autoregulation have been determined as about 50–60 and 150–160 mmHg, respectively . There is much evidence to support the contention that cerebral autoregulation does not maintain constant perfusion through a mean arterial blood pressure range of 60–150 mmHg as is so often cited in the literature . Within the limitation, a slight slope is frequently observed with a small change of cerebral blood flow from 80% to 120% of the baseline . Nonetheless, within the boundaries, cerebral autoregulation is effective. This adaptation not only enables instant cerebral blood flow regulation in register to the neuronal function, but also protects the brain against fatal consequences of hypoxia and energy deficit. In addition, it is noted that the upper and lower boundaries of the plateau phase are not fixed but can be modulated by a plethora of factors such as sympathetic nervous activity, the renin–angiotensin system, and many diseases.

The classic cerebral autoregulation was subsequently substantiated by many brain circulation researchers and became the key dogma of the brain circulation. However, it is important to note that the classic methods permit sampling of regional cerebral blood flow at intervals of minutes. Thus, the classic, or static, cerebral autoregulatory responses might be the consequence of autoregulation but not the process of cerebral autoregulation itself. Modern techniques such as transcranial laser Doppler ultrasonography enable to measure cerebral autoregulatory responses with a much high temporal resolution with the assumption that cerebral blood flow is proportional to blood velocity. Dynamic studies of cerebral autoregulation quantify the fast modifications in cerebral blood flow velocity in a major cerebral artery in relation to rapid alterations in blood pressure within the upper and lower limits of the static cerebral autoregulation. This approach allows differentiation of the cerebral autoregulation response to fluctuations in beat-to-beat blood pressure of different magnitudes and durations. The dynamic studies have identified events of reduced blood flow in the period needed for cerebral blood flow to return to baseline after hypotension . Despite the distinction of long-term steady-state and transient changes in arterial pressure between static and dynamic cerebral autoregulation, the two may represent the same phenomenon of cerebral circulation.

Mechanisms Underlying Cerebral Autoregulation

The mechanisms of cerebral autoregulation remain poorly understood, especially in human. It is clear that cerebral autoregulation is multifactorial phenomenon of the cerebral circulation, including myogenic, autonomic, and metabolic mechanisms ( Fig. 10.1 ).