Brian Michael Thomas Deegan

The relationship between cardiac output and dynamic cerebral autoregulation in humans

Cerebral autoregulation adjusts cerebrovascular resistance in the face of changing perfusion pressures to maintain relatively constant flow. Results from several studies suggest that cardiac output may also play a role. We tested the hypothesis that cerebral blood flow would autoregulate independent of changes in cardiac output. Transient systemic hypotension was induced by thigh-cuff deflation in 19 healthy volunteers (7 women) in both supine and seated positions. Mean arterial pressure (Finapres), cerebral blood flow (transcranial Doppler) in the anterior (ACA) and middle cerebral artery (MCA), beat-by-beat cardiac output (echocardiography), and end-tidal Pco(2) were measured. Autoregulation was assessed using the autoregulatory index (ARI) defined by Tiecks et al. (Tiecks FP, Lam AM, Aaslid R, Newell DW. Stroke 26: 1014-1019, 1995). Cerebral autoregulation was better in the supine position in both the ACA [supine ARI: 5.0 ± 0.21 (mean ± SE), seated ARI: 3.9 ± 0.4, P = 0.01] and MCA (supine ARI: 5.0 ± 0.2, seated ARI: 3.8 ± 0.3, P = 0.004). In contrast, cardiac output responses were not different between positions and did not correlate with cerebral blood flow ARIs. In addition, women had better autoregulation in the ACA (P = 0.046), but not the MCA, despite having the same cardiac output response. These data demonstrate cardiac output does not appear to affect the dynamic cerebral autoregulatory response to sudden hypotension in healthy controls, regardless of posture. These results also highlight the importance of considering sex when studying cerebral autoregulation.

Elderly women regulate brain blood flow better than men do.

Background and Purpose— Orthostatic intolerance and falls differ between sexes and change with age. However, it remains unclear what role cerebral autoregulation may play in this response. This study was designed to determine whether cerebral autoregulation, assessed using transcranial Doppler ultrasound, is more effective in elderly females than in males. Methods— We used transcranial Doppler ultrasound to evaluate cerebral autoregulation in 544 (236 male) subjects older than age 70 years recruited as part of the MOBILIZE Boston study. The MOBILIZE Boston study is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. We assessed CO2 reactivity and transfer function gain, phase, and coherence during 5 minutes of quiet sitting and autoregulatory index during sit-to-stand tests. Results— Male subjects had significantly lower CO2 reactivity (males, 1.10±0.03; females, 1.32±0.43 (cm/s)/%CO2; P<0.001) and autoregulatory indices (males, 4.41±2.44; female, 5.32±2.47; P<0.001), higher transfer function gain (males, 1.34±0.49; females, 1.19±0.43; P=0.002), and lower phase (males, 42.7±23.6; females, 49.4±24.9; P=0.002) in the autoregulatory band, implying less effective cerebral autoregulation. However, reduced autoregulation in males was not below the normal range, indicating autoregulation was intact but less effective. Conclusions— Female subjects were better able to maintain cerebral flow velocities during postural changes and demonstrated better cerebral autoregulation. The mechanisms of sex-based differences in autoregulation remain unclear but may partially explain the higher rates of orthostatic hypotension-related hospitalizations in elderly men.

Gender related differences in cerebral autoregulation in older healthy subjects

Cerebral autoregulation is an intrinsic mechanism of the cerebrovasculature that maintains cerebral blood flow relatively constant over a wide range of blood pressures. Recent studies have shown sex differences in cerebral autoregulation in adolescents and young adults. We evaluated cerebral auturegulation in 419 (186 male) subjects over the age of 70 recruited as part of the MOBILIZE Boston study. CO2 reactivity, transfer function gain and autoregulatory index (ARI) during sit to stand tests were assessed. Female subjects had significantly higher CO2 reactivity (p < 0.001) and vasomotor range (p<0.001) as well as ARI indices (p<0.001) and lower transfer function gain in the autoregulatory band (p=0.001), implying better cerebral autoregulation, than male subjects. The mechanisms of sex based differences in cerebral autoregulation remain unclear, but the results of this study highlight the need for future work to better understand these underlying autoregulatory differences.

Cerebral autoregulation in the vertebral and middle cerebral arteries during combine head upright tilt and lower body negative pressure in healthy humans

The majority of cerebral autoregulation research has focused on the middle cerebral artery. However, many symptoms of presyncope indicate posterior cerebral hypoperfusion. To address this issue, we measured cerebrovascular reactivity, cerebral blood flow velocity and dynamic cerebral autoregulation in the middle cerebral artery and vertebral arteries during orthostatic stress to presyncope in 9 healthy subjects. There was no significant difference in either the decline in cerebral blood flow velocity or indices of dynamic cerebral autoregulation between the middle cerebral and vertebral arteries prior to or during presyncope. In conclusion, there is no significant difference in regulation of blood flow between the vertebral artery and middle cerebral artery in healthy subjects. Further study is required to determine whether or not a difference exists in syncopal patient populations.

Development and evaluation of new blood pressure and heart rate signal analysis techniques to assess orthostatic hypotension and its subtypes.

Orthostatic hypotension (OH) is a clinical condition, which frequently results in symptoms such as syncope, dizziness during standing, weakness, blurred vision and fatigue. It is defined as a sustained drop in blood pressure exceeding 20 mmHg systolic or 10 mmHg diastolic occurring within 3 min of assuming upright posture, and is a common causal factor for falls in the elderly. Since 1986, tilt-table testing has become widely used in the diagnosis of OH. The Finometer provides non-invasive monitoring of haemodynamic changes during tilt-table testing. In this study, new algorithms for parameter extraction from Finometer data were developed, with specific reference to the diagnosis of OH. Algorithms were developed to assess the rates of change of haemodynamic variables in response to head-up tilt testing, a previously unexamined aspect of tilt-table testing. These algorithms were applied to the Finometer measurements of 20 patients, who underwent tilt-table testing in the Mid-Western Regional Hospital, Limerick. The data extraction algorithms were shown to accurately record changes in haemodynamic variables for further analysis. It was also demonstrated that the rate of change of blood pressure during the head-up tilt-table testing could have prognostic significance for OH.

A new blood pressure and heart rate signal analysis technique to assess Orthostatic Hypotension and its subtypes

Orthostatic Hypotension is a sudden drop in blood pressure upon assumption of upright posture. This drop in blood pressure is often results in symptoms such as dizziness, light-headedness, blurred vision, and syncope. Since 1986, tilt table testing has become widely used in the diagnosis of Orthostatic Hypotension. In this study, new algorithms for artifact removal and data extraction in Finometer data were developed. Algorithms were also developed to assess the rates of change of haemodynamic variables in response to head up tilt testing. These algorithms were applied to the Finometer measurements of 20 patients, who underwent tilt table testing in the Mid-Western Regional Hospital, Limerick. The techniques developed were shown to effectively reduce artifact noise without loss of clinically relevant data. The data extraction algorithms were shown to accurately record changes in haemodynamic variables. It was also demonstrated that rate of change of blood pressure during head-up tilt table testing could have prognostic significance for orthostatic hypotension.

Therapeutic use of compression stockings for orthostatic hypotension: an assessment of patient and physician perspectives and practices

BACKGROUND Elastic compression stockings (ECS) can be used as a non-pharmacological therapeutic option for older patients with orthostatic hypotension (OH). We aimed to investigate the practices and views of patients and physicians regarding the use of ECS for OH. METHODS Two surveys were designed. The first was sent to 90 patients known to have been prescribed ECS for OH. This questionnaire included items related to the frequency of use and issues related to non-compliance. The second was sent to 69 consultant physicians in geriatric medicine. This included items related to prescribing practices and perceived patient compliance. RESULTS Sixty-seven patients responded (response rate, 74%) and of those 64% were female. Mean age (SD) was 75.1 years (10.5), range 45-91 years. Thirty-three per cent wore ECS daily, whereas 43% never used them. Over half (51%) of the patients reported difficulty in application and 31% reported discomfort. Those aged 75 or older were more likely to report difficulty in application (P=0.003). Forty-eight physicians responded (response rate, 70%). Eighty-nine per cent prescribe ECS for OH. There were significant differences between the frequency of use reported by patients and predicted by physicians (P<0.001), with physicians less likely to predict daily or non-use. Eighty-nine per cent of physicians predicted that difficulty in application was the main reason for non-compliance. CONCLUSION Although prescribed frequently, the use of ECS in patients with OH is often limited by issues related to practicality. Physicians correctly predicted the main reasons for non-compliance although underestimated the scale of patient compliance with ECS.

Assessment of techniques used to evaluate the effect of posture and cardiac output on Cerebral Autoregulation

In this study, the role of cardiac output in Cerebral Autoregulation was assessed. Mean arterial pressure, cerebral blood flow velocity (middle and anterior cerebral artery), stroke volume, cardiac output, total peripheral resistance and cerebral autoregulatory index were assessed in 3 healthy young males and 4 healthy young females during seated and upright thigh cuff testing. Two different methods (long axis left ventricular echocardiography and Modelflow) of evaluating stroke volume and cardiac output were compared. The results showed that cerebral autoregulation was less effective in the upright posture in all subjects. Females had better autoregulation in the anterior cerebral artery, whereas males had better autoregulation in the middle cerebral artery. Cardiac output does not appear to play an important role in cerebral autoregulation during thigh cuff testing. Estimations of cardiac output and stroke volume did not strongly correlate between Modeflow and long axis left ventricular echocardiography.

Enhancing vestibular function in the elderly with imperceptible electrical stimulation

Age-related loss of vestibular function can result in decrements in gaze stabilization and increased fall risk in the elderly. This study was designed to see if low levels of electrical stochastic noise applied transcutaneously to the vestibular system can improve a gaze stabilization reflex in young and elderly subject groups. Ocular counter-rolling (OCR) using a video-based technique was obtained in 16 subjects during low frequency passive roll tilts. Consistent with previous studies, there was a significant reduction in OCR gains in the elderly compared to the young group. Imperceptible stochastic noise significantly increased OCR in the elderly (Mean 23%, CI: 17–35%). Increases in OCR gain were greatest for those with lowest baseline gain and were negligible in those with normal gain. Since stimulation was effective at low levels undetectable to subjects, stochastic noise may provide a new treatment alternative to enhance vestibular function, specifically otolith-ocular reflexes, in the elderly or patient populations with reduced otolith-ocular function.