Dizziness and vertigo symptoms are common across all ages. Although it is well known that vestibular dysfunction can cause these symptoms, other causes must also be considered. This chapter examines the role of blood pressure and cerebral blood flow regulation and their possible connections to the development of dizziness. Humans have several cardiovascular adaptations that are designed to maintain blood pressure and brain blood flow when upright. The role of the baroreflex in maintaining blood pressure when moving from the supine to upright position is reviewed. Brain blood flow regulation to maintain adequate flow when upright also has been examined. Reductions in brain blood flow have been shown to be associated with the development of dizziness as well as orthostatic hypotension. In addition, there is emerging evidence that the vestibular system assists in this cardiovascular adaptation. Therefore, it is important to consider how vestibular dysfunction may result in orthostatic hypotension or reduced brain blood flow that could cause or worsen symptoms of dizziness.
KeywordsAutonomic, Baroreflex, Cerebral blood flow, Orthostatic, Vestibular
Without a doubt, vestibular dysfunction can cause dizziness; however, other systems that interact with the vestibular system can also be involved. The goal of this chapter is to discuss the role of cardiovascular reflexes in contributing to dizziness.
A common symptom that often causes a patient to seek medical attention for the evaluation of dizziness is presyncope: the feeling of “lightheadedness” before fainting. Even young healthy individuals with intact vestibular systems commonly report dizziness and lightheadedness during tilt table testing. Participants generally report dizziness but not true vertigo. So why are these individuals reporting dizziness during an upright tilt?
Although the mechanism remains unclear, the assumption is that reductions in cerebral blood flow (CBF) result in symptoms associated with presyncope. In fact, recent evidence has found that both orthostatic hypotension (decreased blood pressure when standing) and cerebral hypoperfusion (reduction in brain blood flow) are related to incidents of dizziness. To understand why CBF would be reduced during upright posture requires an understanding of how blood pressure and CBF are regulated when we are standing or when we rise from a supine or seated position. To explore this connection, blood pressure regulation and regulation of brain blood flow are described in this chapter.
In addition, fascinating evolving evidence suggests that the vestibular system provides important signals that assist in the regulation of blood pressure and brain blood flow. This chapter also explores these vestibular connections in the context of their impact on the development of dizziness and vertigo.
Regulation of Blood Pressure
Regulation of blood pressure is essential to health because blood flow through all organs is dependent on adequate driving pressure. To produce that pressure, the heart pumps approximately 86,000 times/day to maintain blood flow and pressure throughout the body. Pressure at the aorta, where blood is ejected from the left ventricle, is determined by the following equation:
MAP = CO × TPR
Humans are bipedal and, unlike quadrupeds, during upright standing, there is a significant distance between the head and the feet. This unique posture results in substantial movement of blood from the upper torso to the legs ( Fig. 15.1 ).
Sufficient cardiac output is required to maintain blood pressure (MAP; Eq. 15.1 ). Cardiac output is the product of heart rate and stroke volume, and stroke volume is determined by venous return (the amount of blood returning to the heart); therefore, assumption of the upright position results in considerable reduction in venous return. The result of this reduction in venous return is a drop in mean arterial blood pressure, which if uncompensated results in syncope (i.e., loss of consciousness). An example of this response was demonstrated in a group of elderly males and females who participated in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly (MOBILIZE) Boston study ( Fig. 15.2 ).
Note that within 10 seconds of initiating the stand, the participants had roughly a 20-mmHg drop in mean arterial pressure (MAP). The decrease in pressure was transient, and by 30 seconds the blood pressure had returned to baseline levels. This regulation of blood pressure is essential to maintaining consciousness. Returning to Eq. (15.1) , some variables can be modified to maintain pressure. One of these variables is cardiac output, which is dependent on the stroke volume and heart rate. When humans stand upright, there is translocation of blood to the lower limbs and reduction in stroke volume. This results in a reduction in arterial pressure as seen in Fig. 15.2 . To return blood pressure to normal levels, there is a need to modify (increase) the heart rate and/or resistance, which is accomplished by the baroreflex.
Baroreflex Regulation of Blood Pressure
The baroreflex is a mechanism that regulates blood pressure in response to sudden pressure changes. The baroreflex senses pressure changes through stretch receptors located in the aortic arch and carotid arteries at the bifurcation of the common carotid artery into the external and internal carotid arteries. Stretch of these arteries is interpreted as an increase in pressure and results in increased neural firing ( Fig. 15.3 ). These neural signals result in the activation of cardiovascular control centers in the brainstem, which in turn results in changes in the heart rate and resistance. The detailed neural networks involved in the baroreflex response are well described but beyond the scope of this chapter.
Briefly, the baroreflex is able to modulate the heart rate by activating the autonomic nervous system, which directly controls the heart rate. By activating the parasympathetic system, the heart rate slows , and this effect can occur within one beat. Heart rate control under 100 beats per minute is primarily parasympathetic mediated, so the fastest response to a decrease in blood pressure is parasympathetic withdrawal , which allows the heart rate to increase immediately. The baroreflex can cause an increase not only in the heart rate by decreasing parasympathetic tone but also in the contractility of the heart by increasing sympathetic activity to the heart. However, this mechanism is more likely to predominate at higher heart rates, such as those achieved during exercise.
The other baroreflex-mediated response to blood pressure changes is to change peripheral vascular resistance. In humans, parasympathetic activity seems to have little effect on vascular resistance, unlike in many quadrupeds. In contrast, increases in sympathetic activity to the peripheral vessels result in vasoconstriction and an increase in peripheral vascular resistance.
To return to how humans respond to assuming the upright posture, Fig. 15.2 illustrates that there is a reduction in blood pressure. This is sensed by the stretch receptors, resulting in the baroreflex initiating an immediate increase in the heart rate to compensate for the decrease in stroke volume caused by blood moving into the lower limbs. As can be seen in Fig. 15.2 , there is an immediate increase in the heart rate resulting from baroreflex-mediated parasympathetic withdrawal. Despite the increase in heart rate, blood pressure continues to fall. At the same time as the heart rate increases, to maintain mean arterial blood pressure, there is a baroreflex-mediated increase in sympathetic activity to peripheral blood vessels resulting in vasoconstriction. This increase in resistance, which takes approximately 10 seconds, results in increased total peripheral resistance and thus increased MAP ( Eq. 15.1 ; MAP = CO × TPR). As can be seen in Fig. 15.2 , roughly 10 seconds after standing, blood pressure begins to rise and returns to baseline levels in approximately 25 seconds. One can also see that the heart rate begins to decrease within 20 seconds after standing, as resistance compensates for reduced stroke volume.
Returning to the discussion of what this has to do with dizziness and vertigo, without this baroreflex response to drops in pressure, humans would be unable to maintain adequate blood flow to the brain when standing, which would produce dizziness (presyncope) and even loss of consciousness. In fact, in a study of 11,429 patients, orthostatic hypotension (i.e., abnormally low blood pressure when upright) in the first minute of standing was strongly related to dizziness. Because that first minute is the period during which the baroreflex must adjust for the shift of blood into the lower limbs, these data highlight the importance of considering the baroreflex and blood pressure regulation in patients with dizziness, especially when dizziness occurs after standing.
It is well known that aging results in blunting of the baroreflex. This is thought to be the result of stiffening of large vessels, which reduces stretch during changes in blood pressure. Thus, if the same pressure decrease results in an attenuated stretch because of vessel stiffening, an inappropriately low or diminished heart rate increase would be expected. Furthermore, aging processes appear to hinder the ability of increased sympathetic outflow to effect vasoconstriction and increased resistance. Thus elderly individuals are at a greater risk for orthostatic hypotension, which produces dizziness. In addition, some blood pressure medications (e.g., alpha blockers, calcium channel blockers) dampen the ability of peripheral blood vessels to vasoconstrict, and other blood pressure medications (e.g., beta blockers) do not allow the heart to increase its rate to maintain blood pressure.
Thus far this chapter has focused on blood pressure regulation based on the assumption that orthostatic hypotension could be contributing to reductions in CBF and thus the development of dizziness. However, the picture is more complicated than this. It is necessary to understand how CBF is regulated to examine its possible role in dizziness.
Regulation of Brain Blood Flow
Regulation of CBF is critical for proper neural function. Therefore alterations in CBF regulation caused by aging or age-related disease may have important clinical consequences, such as cognitive impairment, gait disorders, falls, and the development of symptoms such as dizziness. This section reviews mechanisms of CBF regulation and their changes with hypertension and aging, with particular attention to the possible etiologies of dizziness in some patients.
The regulation of CBF involves several interacting mechanisms. Barcroft in 1914 proposed that the cerebral flow was matched to metabolic demands. This has since been validated in both animal and human studies. Cognitive activation in humans increases both global and local blood flow to the brain. The ability to augment flow is critical, for example, cognitive deficits with cerebral ischemia are reversed by increases in global CBF. Despite the fact that vasodilation occurs locally around activated neurons because of neurovascular coupling, this vasodilation may be insufficient if global cerebral flow is significantly reduced. To ensure sufficient CBF is available, cerebral vessels must dilate or constrict in response to the prevailing blood pressure. The ability to maintain brain blood flow over a wide range of pressures is termed cerebral autoregulation. Thus, impairment of cerebral autoregulation could adversely affect global CBF during orthostatic hypotension.
Autoregulation of Cerebral Blood Flow
Cerebral autoregulation maintains blood flow relatively constant across a wide range of cerebral perfusion pressures (CPPs). CBF is determined by CPP and cerebrovascular resistance (CVR), with CPP being a result of arterial pressure minus intracranial pressure. The relationship between these variables can be defined as:
CBF = CPP CVR
Thus, vascular resistance must be adjusted to maintain CBF constant in the face of changing perfusion pressure. This is accomplished by dilation of cerebral vessels. Fig. 15.4 demonstrates that within a normal pressure range, CVR adjusts to the prevailing CPP to maintain flow relatively constant. When pressure becomes excessively low, resulting in maximal vasodilation, resistance can no longer adjust to decreasing perfusion pressures and CBF falls. In contrast, when pressures become too high, cerebral vessels are forced open by the driving pressure and thus resistance decreases, resulting in an increase in CBF. This condition is termed autoregulatory breakthrough.
Why is cerebral autoregulation important in the consideration of other mechanisms that may contribute to dizziness? Most people have had the experience of getting up quickly in the morning, becoming lightheaded, and needing to sit down again. The reason for this lies in the CBF response to the sudden pressure change associated with the change in posture from supine to upright. The cerebral flow velocity response has been examined by studying the response of individuals to a change in pressure during a “sit to stand” maneuver or induced by release of two thigh cuffs that were inflated above systolic blood pressure for 3 min.
Three important events preceding the baroreflex are highlighted in Fig. 15.5 : the first is initiation of the blood pressure drop (marked by dotted lines at time point 0), the second is the nadir of the cerebral flow velocity response (dotted lines at approximately 4 seconds), and the third event is when cerebral flow velocity has returned to baseline levels (dotted lines at approximately 11 seconds). Fig. 15.5 demonstrates that blood pressure continues to drop after the flow velocity has hit its nadir. It is also important to note that CBF velocity returns to baseline before blood pressure returns to baseline. Recall that, according to Eq. (15.2) , CBF is driven by the pressure unless resistance is changed. These data indicate that cerebral vessels must dilate to improve CBF before baroreflex return of CBF to baseline. This is cerebral autoregulation in action. Thus, when cerebral autoregulation is impaired, CBF continues to decrease when blood pressure drops, likely producing symptoms of dizziness, as has been reported in a group of patients with Parkinson disease and patients referred to an autonomic clinic.
Although autoregulation is an important mechanism, previous research has found that autoregulation is fairly robust. It is well known that changing arterial carbon dioxide levels results in changes in CBF without affecting cerebral autoregulation. Similarly, stimulation of the fastigial nucleus in primates has been found to result in vasodilation, which causes increases in CBF without affecting autoregulation. This vasodilation may be mediated by parasympathetic pathways. Autoregulation even seems to be maintained during hypotension in both chronic local cerebral hypoperfusion and orthostatic hypotension.
An increased sympathetic outflow caused by the baroreflex is another possible mechanism by which cerebral autoregulation could be altered. There is some evidence of decreased ability to regulate CBF during pressure fluctuations caused by lower body negative pressure or upright tilt. However, early studies of cats found no effect of acute sympathetic denervation on autoregulatory responses. Consistent with this, animal studies have found no effect on autoregulation from chronic or acute sympathetic denervation or from electrical stimulation when blood pressure is kept stable. In humans, sympathetic activation caused by upright tilt does not impair the ability to regulate against pressure fluctuations, despite creating decreases in cerebral flow velocity similar to previous studies, all to suggest that sympathetic activation does not impair cerebral autoregulation.
Thus, based on these data, it seems that the cerebral autoregulatory system is robust and that reduction in CBF caused by an inability of the cerebral autoregulatory system to handle pressure changes is unlikely, although no studies have examined the relationship between cerebral autoregulation and dizziness. However, other mechanisms related to aging may affect the baroreflex, resulting in cerebral hypoperfusion.
Effects of Age on Cerebral Blood Flow
Aging is associated with a well-documented decrease in global CBF and an increase in cerebral vascular resistance. This raises the question of whether aging may impair cerebral autoregulation and thus contribute to cerebral hypoperfusion in the elderly. In fact, previous work has demonstrated that older rats are less able to tolerate hypotensive stimuli, have reduced cerebrovascular reactivity to CO 2 (often used as an indicator of intact autoregulation), and have an increased lower limit of autoregulation. These findings suggest that autoregulation could be impaired as a result of aging.
Studies of CBF in elderly humans have produced conflicting results. Studies that examined the response to changes in arterial CO 2 levels have reported that aging either has no effect on cerebrovascular reactivity or is associated with reduced reactivity. Myogenic tone in isolated human pial arteries was found to be unaffected by age, suggesting intact autoregulatory capacity. Furthermore, measures of cerebral autoregulation in elderly humans, based on the response of CBF to spontaneous fluctuations in blood pressure, have found that autoregulation remains intact.
In fact, in the largest study of autoregulation in an elderly population, Deegan et al. found that cerebral autoregulation remained intact as shown in ( Fig. 15.6 ). It has been suggested in a smaller cross-sectional dataset that autoregulation may be impaired as individuals get older, but this is in contrast to the many studies that have found intact autoregulation.