Clive M. Brown

Vascular responses to orthostatic stress in patients with postural tachycardia syndrome (POTS), in patients with low orthostatic tolerance, and in asymptomatic controls

Patients with postural tachycardia syndrome (POTS) are characterized by development of symptoms of orthostatic intolerance during standing that are not because of hypotension but are associated with tachycardia. The goal of this study was to compare the cardiac and vascular responses to orthostatic stress for patients with POTS (n=8) with those for patients with low orthostatic tolerance (n=29) and for healthy control subjects (n=12). Responses of heart rate (ECG), arterial blood pressure, and brachial artery blood velocity (Doppler) were determined during a progressive orthostatic stress test of head-up tilt and lower body suction. Changes in forearm vascular resistance (mean arterial pressure/brachial velocity) were less for patients with POTS than for healthy persons, and also less than for most of the patients with low orthostatic tolerance. However, patients with POTS did not have a low tolerance to orthostatic stress (measured as time to discontinuation of the test). For the patients with POTS, the test was discontinued often because of symptoms associated with tachycardia but not hypotension, whereas for the other two groups, the test was discontinued because of hypotension. This study shows that for patients with POTS, abnormal sympathetic responses exist, with an increased sympathetic drive to the heart but deficient peripheral vascular responses, as measured in the forearm. This supports the hypothesis that patients with POTS may have a selective peripheral neuropathy, with small responses in some regions being compensated by overactivity in other regions.Patients with postural tachycardia syndrome (POTS) are characterized by development of symptoms of orthostatic intolerance during standing that are not because of hypotension but are associated with tachycardia. The goal of this study was to compare the cardiac and vascular responses to orthostatic stress for patients with POTS (n=8) with those for patients with low orthostatic tolerance (n=29) and for healthy control subjects (n=12). Responses of heart rate (ECG), arterial blood pressure, and brachial artery blood velocity (Doppler) were determined during a progressive orthostatic stress test of head-up tilt and lower body suction. Changes in forearm vascular resistance (mean arterial pressure/brachial velocity) were less for patients with POTS than for healthy persons, and also less than for most of the patients with low orthostatic tolerance. However, patients with POTS did not have a low tolerance to orthostatic stress (measured as time to discontinuation of the test). For the patients with POTS, the test was discontinued often because of symptoms associated with tachycardia but not hypotension, whereas for the other two groups, the test was discontinued because of hypotension. This study shows that for patients with POTS, abnormal sympathetic responses exist, with an increased sympathetic drive to the heart but deficient peripheral vascular responses, as measured in the forearm. This supports the hypothesis that patients with POTS may have a selective peripheral neuropathy, with small responses in some regions being compensated by overactivity in other regions.

Effect of cold face stimulation on cerebral blood flow in humans.

BACKGROUND AND PURPOSE In humans, activation of the diving reflex by a cold stimulus to the face results in bradycardia, peripheral vasoconstriction and an increase in blood pressure. However, responses of the cerebral blood flow have not yet been evaluated. We undertook this study to assess the effect of cold face stimulation on the cerebral circulation in humans. METHODS Seventeen healthy volunteers, aged 27+/-5 years were evaluated during application of a cold stimulus (0 degrees C) to the forehead for 60s. We continuously monitored mean arterial pressure (MAP), mean flow velocity (MFV) of the middle cerebral artery, cardiac output, skin blood flow, heart rate and end-tidal CO2. Total peripheral resistance (TPR) was calculated as MAP divided by cardiac output. Cerebrovascular resistance index (CVRi) was calculated as MAP divided by MFV. RESULTS Cold face stimulation did not significantly affect cardiac output but resulted in significant decreases in heart rate and skin blood flow and an increase in MAP. MFV in the mid-cerebral artery showed a slight, but significant increase. The maximum increase in CVRi (14.2+/-11.4%) was significantly (P<0.01) less than the maximum increase in TPR (23.9+/-5.7%). End-tidal CO2 did not change significantly during the cold stimulation. CONCLUSIONS In contrast to other sympathetic stimulations (e.g. lower body negative pressure), facial cooling results in an increase in cerebral blood flow. The amount of cerebral vasoconstriction was less than the amount of total peripheral vasoconstriction. These results suggest that although there is some constriction of the cerebral resistance vessels during cold face stimulation, cerebral perfusion was maintained, possibly by opposing parasympathetic activation.

Abnormal heart rate and blood pressure responses to baroreflex stimulation in multiple sclerosis patients

Cardiovascular autonomic neuropathy has been previously reported in patients with multiple sclerosis (MS) using standard reflex tests. However, no study has separately evaluated both parasympathetic and sympathetic cardiovascular autonomic regulation. We therefore assessed the baroreflex-mediated vagal and sympathetic control of the heart rate and sympathetic control of the blood vessels in MS patients using sinusoidal neck stimulation.We studied 13 multiple sclerosis patients aged 28–58 years and 18 healthy controls aged 26–58 years. The carotid baroreflex was stimulated by sinusoidal neck suction (0 to –30 mmHg) at 0.1 Hz to assess the autonomic control of the heart and blood vessels, and at 0.2 Hz to assess the vagal control of the heart. Continuous recordings were made of blood pressure, electrocardiographic RR-interval and respiration, with breathing paced at 0.25 Hz. Spectral analysis was used to evaluate the magnitude of the low frequency (LF, 0.03–0.14 Hz) and high frequency (HF, 0.15–0.50 Hz) oscillations in RR-interval and blood pressure in response to the sinusoidal baroreceptor stimulation. Responses to the applied stimulus were assessed as the change in the spectral power of the RR-interval and blood pressure fluctuations at the stimulating frequency from the baseline values.The increase in the power of 0.1 Hz RR-interval oscillations during the 0.1 Hz neck suction was significantly smaller (p<0.01) in the MS patients (4.47±0.27 to 5.62±0.25 ln ms2) than in the controls (4.12±0.37 to 6.82±0.33 ln ms2). The increase in the power of 0.1 Hz systolic BP oscillations during 0.1 Hz neck suction was also significantly smaller (p<0.01) in the MS patients (0.99±0.19 to 1.96±0.39mmHg2) than in the healthy controls (1.27±0.34 to 9.01±4.10mmHg2). Neck suction at 0.2 Hz induced RR-interval oscillations at 0.2 Hz that were significantly smaller (p<0.05) in the patients (3.22±0.45 ln ms2) than in the controls (5.27±0.29 ln ms2). These results indicate that in MS patients, baroreflex dysfunction is not only restricted to the cardiovagal limb of the baroreflex, but that the sympathetic modulation of the blood vessels is also affected.

Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation.

The aim of this study was to determine whether lower body negative pressure (LBNP), combined with noninvasive methods of assessing changes in systemic and cerebral vascular resistance, is suitable as a method for assessing cerebral autoregulation. In 13 subjects we continuously assessed heart rate, blood pressure, cerebral blood flow velocity (CBFV) and cardiac output during graded levels of LBNP from 0 to -50 mm Hg. With increasing levels of LBNP, cardiac output declined significantly (to 55.8+/-4.5% of baseline value) but there was no overall change in mean arterial pressure. CBFV also fell at higher levels of LBNP (to 81.4+/-3.2% of baseline) but the percentage CBFV change was significantly less than that in cardiac output (P<0.01). The maximum increase in cerebrovascular resistance (pulsatility ratio) was significantly less than that in total peripheral resistance (17+/-6% vs. 105+/-16%, P<0.01). Spectral analysis showed that the power of low-frequency oscillations in mean arterial pressure, but not CBFV, increased significantly at the -50 mm Hg level of LBNP. These results show that, even during high levels of orthostatic stress, cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation. Furthermore, assessment of cardiovascular and cerebrovascular parameters during LBNP may provide a useful clinical test of cerebral autoregulation.

Effects of age on the cardiac and vascular limbs of the arterial baroreflex

Background Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex‐mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels.

Impairment of parasympathetic baroreflex responses in migraine patients

Objectives –  The aim of this study was to assess baroreflex regulation of the heart rate and blood vessels in migraine patients in comparison with healthy controls.

Dynamic cerebral autoregulation is impaired in glaucoma.

OBJECTIVES Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. MATERIALS AND METHODS In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. RESULTS 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68+/-1.2 cm(2) s(-2)) and POAG (6.79+/-2.1 cm(2) s(-2)) than in controls (2.40+/-0.4 cm(2) s(-2)). Furthermore, the MAP-CBFV gain was higher in NPG (2.44+/-0.5 arbitrary units [a.u.]) and POAG (1.99+/-0.2 a.u.) than in controls (1.21+/-0.1 a.u.). CONCLUSION Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type II diabetes mellitus

Background In diabetic patients, impairment of the cardiovagal limb of the baroreflex has been well established. However, the role of sympathetic mediated baroreflex vasomotor control of the blood vessels is not well defined. We therefore assessed the vasomotor responses to sinusoidal baroreceptor stimulation in diabetic patients.

Delayed Cerebrovascular Autoregulatory Response to Ergometer Exercise in Normotensive Elderly Humans

Background: Relatively little is known about physiological cerebrovascular haemodynamics during physical stress in elderly healthy individuals. The aim of this study was to determine the effect of ergometer stress on cerebrovascular haemodynamics in elderly healthy individuals in comparison with young healthy individuals, using non-invasive methods. Methods: Continuous middle cerebral artery blood flow velocity (CBFV; transcranial Doppler ultrasound), beat-to-beat blood pressure, heart rate and transcutaneous pCO2 were measured in response to 3 min ergometer exercise stress in 18 elderly healthy subjects (mean age ± SD 66.5 ± 5.8 years) and 18 healthy young subjects (mean age ± SD 29.4 ± 4.7 years). Pulsatility index (PI) was used as a parameter for cerebrovascular resistance. The subjects were in a supine position with an elevated trunk and performed exercise by pedalling on an ergometer, generating 75–100 W. Statistical analysis was carried out using MANOVA, a general linear model with repeated measures. Results: In both groups, blood pressure increased significantly (p < 0.001) with time during exercise, with no significant differences between the groups or regarding interaction (time sequence/group factor). Heart rate increased significantly with time during exercise (p < 0.001) and was significantly more prominent (p = 0.002) and prolonged (p < 0.001) in the young group. pCO2 did not differ with time or between the groups and with regard to interaction. Mean CBFV (MFV) increased significantly during time (p < 0.001). Between the groups, there was no significant difference (p = 0.836), but with regard to interaction (time sequence/group factor), there was a significant delay in MFV increase in the group of young subjects (p = 0.002). The PI, a measure of cerebrovascular resistance, increased significantly with time without significant differences between the groups (p = 0.061), but was significantly delayed in the elderly regarding the interaction time sequence/group factor (p < 0.001). Conclusion: The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (predominantly neurogenic and myogenic). In healthy normotensive elderly subjects, cerebral autoregulatory capacity is retained but delayed in response to ergometer stress compared with young healthy subjects. We speculate that these findings may contribute to a higher risk of cerebral hypoperfusion in the elderly.

Orthostatic challenge reveals impaired vascular resistance control, but normal venous pooling and capillary filtration in familial dysautonomia.

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.