Transfer function analysis of spontaneous fluctuations in BP (blood pressure) and CBFV (cerebral blood flow velocity) has been widely used to study dynamic CA (cerebral autoregulation). The inverse Fourier transform and its integral, giving the impulse and step responses, have been used to gain perspective of the state of dynamic CA from the frequency and time domains respectively. The occurrence of ectopic heartbeats in the data has usually been treated as an artefact. Data containing multiple ectopic heartbeats were selected from a data set compiled for an acute stroke study which also included bilateral middle CBFV, concurrent surface ECG and non-invasive beat-to-beat BP recordings. Transfer function analysis and impulse and step responses were calculated from these data by (i) retaining ectopic heartbeats, (ii) after removal of ectopic heartbeats and replacement by linear interpolation, and (iii) using a narrow window of data surrounding selected ectopic heartbeats. Coherent averaging of the raw data of the selected ectopic heartbeats also allowed direct visualization of the relationship between BP changes and CBFV. The impulse and step responses were similar in shape whether or not ectopic heartbeats had been removed and showed characteristics of active dynamic CA. Removal of ectopic heartbeats from the CBFV and BP tracings, by linear interpolation or other methods, is not necessary to provide reliable estimates of dynamic autoregulation in subjects with ectopic heartbeat rates of up to eight per min. Additionally, impulse-like disturbances of BP induced by single-beat ectopic heartbeats provide enough information to characterize the autoregulatory response of the subject in agreement with more traditional methods of dynamic autoregulation assessment.

Cardiac BRS (baroreceptor reflex sensitivity) is impaired following ischaemic stroke and predicts the risk of subsequent long-term death and disability. Impaired cardiac BRS may be due to impaired central processing of baroreceptor information following stroke or reduced baroreceptor activity due to increased large artery stiffness. We evaluated the relationship between large (aortic) artery stiffness and cardiac BRS during the acute phase of ischaemic stroke and in comparison with a group of stroke-free control subjects. Thirty-one ischaemic stroke patients were studied within 48 h of onset and again on day 14, along with 26 control subjects free of cerebrovascular disease. Cardiac BRS (determined by spectral analyses) and arterial stiffness estimated by PWVcf (carotid–femoral pulse wave velocity) using applanation tonometry were obtained. At baseline, cardiac BRS was lower in the stroke compared with the control group (4.3±2.3 compared with 6.5±4.2 ms/mmHg; P <0.05). Cardiac BRS values were correlated with PWVcf at <48 h ( r =−0.51, P <0.01) and on day 14 ( r =−0.54, P <0.01), but not in the control group ( r =−0.27, P =not significant). In quantile regression models, taking into account the effect of all cardiovascular variables, cardiac BRS was independently related to PWVcf at baseline and on day 14 in the stroke patients, but stroke was not related to cardiac BRS level when other cardiovascular variables were considered. Wall stiffness of the arterial vessels involved in the baroreflex arc may account for, at least in part, the reduced cardiac BRS observed in acute stroke patients.

Transfer function analysis has become one of the main techniques to study the dynamic relationship between cerebral blood flow and arterial blood pressure, but the influence of different respiratory rates on cerebral blood flow has not been fully investigated. In 14 healthy volunteers, middle cerebral artery blood flow velocity, recorded using transcranial Doppler ultrasound, non-invasive beat-to-beat Finapres blood pressure, ECG and end-tidal CO 2 ( P ETCO 2 ) levels were recorded with subjects resting supine and breathing spontaneously or at controlled rates of 6, 10 and 15 breaths/min. Transfer function analysis and impulse and step responses were computed at each respiratory rate. P ETCO 2 levels tended to fall slightly during paced respiration, especially at 15 breaths/min. Controlled breathing rates did not alter transfer function analysis in the frequency range below 0.08 Hz but, above this frequency, the coherence function contained significant peaks corresponding to the respiratory frequencies. The impulse response was similar at all breathing rates, but the step response was characteristic of more efficient autoregulation with reduced P ETCO 2 levels associated with increasing respiratory rate. The effects of breathing rate and rhythmicity and P ETCO 2 must be considered in studies of cerebral autoregulation.

The cerebrovascular changes that occur prior to vasovagal syncope (VVS) are unclear, with both increases and decreases in cerebrovascular resistance being reported during pre-syncope. This study assessed the cerebrovascular responses, and their potential underlying mechanisms, that occurred before VVS induced by head-up tilt (HUT). Groups of 65 normal subjects with no previous history of syncope and of 16 patients with recurrent VVS were subjected to 70° HUT for up to 30min. Bilateral middle cerebral artery (MCA) cerebral blood flow velocities (CBFVs) were measured using transcranial Doppler ultrasound, along with simultaneous measures of MCA blood pressure, heart rate, and end-tidal and transcutaneous carbon dioxide concentrations. All 16 patients and 14 of the control subjects developed VVS during HUT. During pre-syncope, mean CBFV declined, due predominantly to a decrease in diastolic rather than systolic CBFV (decreases of 44.5±;19.8% and 6.3±;12.9% respectively; P < 0.0001). CO 2 levels and indices of cerebrovascular resistance decreased during pre-syncope, while critical closing pressure (CrCP) increased to levels approaching MCA diastolic blood pressure before decreasing precipitously on syncope. Pre-syncopal changes were similar in syncopal patients and syncopal controls. CrCP, therefore, rises during pre-syncope, possibly related to progressive hypocapnia, and may account for the relatively greater fall in diastolic CBFV. Falls in cerebrovascular resistance, therefore, may be offset by rises in CrCP due to hypocapnia, leading to diminished cerebral blood flow during pre-syncope.

Normal pregnancy is associated with marked changes in cardiovascular haemodynamics, which in part may be due to changes in autonomic control mechanisms. Baroreflex sensitivity for heart rate (BRS) was calculated in the supine and standing positions using power spectral analysis of pulse interval (PI) and systolic blood pressure (SBP) in 16 normotensive pregnant women and 10 normotensive non-pregnant controls. The pregnant women were studied on three occasions during their pregnancy (early, mid- and late gestation) and once during the puerperium. Supine total SBP variability increased between early and late pregnancy by 79% [95% confidence intervals (CI) 30%, 145%; P < 0.001], and supine high-frequency PI variability decreased by 75% (CI 51%, 88%; P < 0.001). Supine BRS fell by 50% ( P < 0.001), with values returning to early-pregnancy levels in the puerperium, which were similar to those recorded in the control group. Standing SBP variability and BRS values were unchanged during pregnancy and post partum. The low/high frequency ratio of PI variability, taken as a surrogate measure of sympathovagal balance, increased by 137% (CI 42%, 296%; P < 0.01) in the supine but not the standing position from early to late pregnancy. This was due to a decrease in high-frequency variability rather than to an increase in low-frequency variability, suggesting that these changes may have been due to vagal withdrawal rather than increased sympathetic activity. Normotensive pregnancy is associated with a marked decrease in supine BRS, although the exact mechanisms for these changes remain unclear. Further studies are required to define whether changes in BRS and sympathovagal tone in early pregnancy can be used to predict the onset of pregnancy-induced hypertension.

1. There has been considerable interest in techniques recently developed for the study of arterial baroreceptor—cardiac reflex sensitivity based on analysis of spontaneous baroreflex sequences and on spectral analysis. This study examined how these newer techniques agreed with the established pharmacological methods in elderly subjects. 2. In 20 elderly subjects [10 hypertensive (clinic blood pressure 180 ± 4/88 ± 2 mmHg) and 10 normotensive (clinic blood pressure 136 ± 3/73 ± 2 mmHg)], we assessed baroreflex sensitivity from spontaneous sequences of increasing and decreasing blood pressure and pulse interval and their mean, and from spectral analysis to derive α, the index of overall baroreflex gain. Pharmacological baroreflex sensitivity was derived from the blood pressure and pulse interval responses to depressor (sodium nitroprusside) and pressor (phenylephrine) stimuli, and their mean. 3. Baroreflex sensitivity was significantly lower in the hypertensive group by the pharmacological, sequence and spectral methods (all P < 0.05). 4. There was acceptable agreement between pharmacological baroreflex sensitivity and sequences of the same direction, but with some systematic bias. There was also reasonable agreement between pharmacological and spectral baroreflex sensitivity and close agreement without bias between sequence and spectral methods. 5. The newer and established techniques demonstrate acceptable agreement in the elderly, albeit with some systematic bias. Pharmacological methods have enjoyed historical precedence but newer techniques give equivalent results, and are preferable in some circumstances. The newer techniques may be more descriptive of the spontaneous behaviour of the arterial baroreflex at rest rather than under artificially stimulated conditions.

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects. 2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60–76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive. 3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with N G -nitro- l -arginine to inhibit nitric oxide synthase. 4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside. 5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R—R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor—cardiac reflex from the linear relation of the change in R—R interval to the increasing systolic blood pressure measured noninvasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 ± 112.9 versus 459.3 ± 189.8 ms 2 , mean ± SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 ± 1.6 versus 9.5 ± 2.5 ms/mmHg, mean ± SD, P > 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes ( P > 0.001) and poor diabetic control ( P > 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor—cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.