Cerebral blood flow and metabolism during exercise

Abstract

During exercise regional cerebral blood flow (rCBF), as blood velocity in major cerebral arteries and also blood flow in the internal carotid artery increase, suggesting an increase in blood flow to a large part of the brain. Such an increase in CBF is independent of the concomitant increase in blood pressure but is modified by the alteration in arterial carbon dioxide tension (PaCO₂). Also, the increase in middle cerebral artery mean blood velocity (MCA V_mean) reported with exercise appears to depend on the ability to increase cardiac output (CO), as demonstrated in response to beta-1 blockade and in patients with cardiac insufficiency or atrial fibrillation.

Near-infrared spectroscopy (NIRS) determined cerebral oxygenation supports the alterations in MCA V_mean during exercise. Equally, the observation that the cerebrovascular CO₂-reactivity appears to be smaller in the standing than in the sitting and especially in the supine position could relate to the progressively smaller CO.

In contrast, during exercise “global” cerebral blood flow (gCBF), as determined by the Kety–Schmidt technique is regarded as being constant. One limitation of the Kety–Schmidt method for measuring CBF is that blood flow in the two internal jugular veins depends on the origin of drainage and it has not been defined which internal jugular venous flow is evaluated. Such a consideration is equally relevant for an evaluation of cerebral metabolism during exercise.

While the regional cerebral uptake of oxygen (O₂) increases during exercise, the global value is regarded as being constant. Yet, during high intensity exercise lactate is taken up by the brain and its O₂ uptake also increases. Furthermore, in the initial minutes of recovery immediately following exercise, brain glucose and O₂ uptake are elevated and lactate uptake remains high.

A maintained substrate uptake by the brain after exercise suggests a role for brain glycogen in cerebral activation, but the fate of brain substrate uptake has not yet been determined.

Introduction

Since Kety and Schmidt (1945) developed the nitrous oxide (N₂O) method for measuring CBF, the “global” value (gCBF) and equally the brain metabolic rate have been determined in a variety of circumstances. It was concluded that gCBF is regulated to remain stable for as long as PaCO₂ is stable and blood pressure stays within the range of cerebral “autoregulation” with the range of mean arterial pressure (MAP) from 60 to 150 mm Hg (Lassen, 1959). Thus, exercise does not elevate gCBF, even though blood pressure increases (Madsen et al., 1993). Only in response to mental stimulation is gCBF increased, as is the metabolic rate of the brain (Madsen et al., 1995b) and, conversely, both are reduced during sleep (Madsen et al., 1991). As techniques were developed to evaluate clearance of radioactive substances from the brain, interest was directed to the regional changes in the brain during “activation” (Lassen et al., 1978). The brain was mapped with respect to the blood flow distribution following a given intervention and in contrast to the global evaluation of CBF, there appeared to be an increase in blood flow and in the metabolic rate corresponding to the cortical representation of the sensory input. During a hand movement there is an increase in blood flow as well as in O₂ uptake corresponding to the cortical representation of the sensory input (Raichle et al., 1976), but, as mentioned, during cycling neither flow nor the O₂ uptake change at the global level (Madsen et al., 1993). This discrepancy between a global and regional evaluation of CBF may be due to a relative insensitivity of the Kety–Schmidt technique as well as to the small cortical representation of the hand and the leg. In addition, any alterations in PaCO₂ during exercise may contribute to make a comparison between rest and exercise difficult, while PaCO₂ does not affect an evaluation of the regional flow distribution.

During supine rest the brain as a whole is estimated to receive ∼750 ml min⁻¹ of blood or ∼55 ml (100) g⁻¹ min⁻¹ and a similar value is derived in a variety of situations by changing the diameter of the resistance of vessels in response to, e.g. a change in perfusion pressure (Paulson et al., 1990). Only when blood pressure increases beyond the range of cerebral “autoregulation”, is there a proportional increase in gCBF and, conversely, blood flow decreases when blood pressure drops below ∼60 mm Hg. Also, PaCO₂ has a strong effect on gCBF. CO₂ inhalation increases gCBF 20–30% per kPa PaCO₂. Besides the global influences of blood pressure and PaCO₂ on CBF, local metabolic regulation of regional perfusion is exhibited as flow is coupled specifically to discrete regions of the brain activated during, e.g., motor or visual stimulation. Therefore, autoregulation, PaCO_2, and the local metabolic activity are integrated in the CBF response to a given stimulus including exercise. However, these factors do not seem to account fully for changes in CBF. For instance, with a reduced central blood volume developed during lower body negative pressure (Giller et al., 1992, Levine et al., 1994, Bonder et al., 1995, Schondorf et al., 1997, Zhang et al., 1997, Zhang et al., 1998) or head-up tilt (Jørgensen et al., 1993b, Jordan et al., 1998), MCA V_mean is reduced and NIRS determined cerebral oxygenation decreases (Madsen et al., 1998b), although blood pressure is maintained at the level of supine rest. Also, in the awake dog, CBF is reduced during atrial fibrillation, even when the aortic pressure remains stable (Friedman et al., 1987).

The exercise CBF has been reviewed by Jørgensen (1995) with the main focus on the applicability of transcranial Doppler for CBF and she recently re-evaluated exercise CBF (Jørgensen et al., 1999). This review addresses whether CBF and cerebral metabolic rate increase out of proportion to changes in PaCO₂ and blood pressure during exercise. Additionally, the paper considers to what extent the ability of the subject to increase cardiac output influences brain circulation during exercise. Furthermore, we address whether cerebral metabolic rate changes during exercise and recovery including an evaluation of brain lactate uptake.