J. Andrew Taylor

Short-term cardiovascular oscillations in man: measuring and modelling the physiologies.

Research into cardiovascular variabilities intersects both human physiology and quantitative modelling. This is because respiratory and Mayer wave (or 10 s) cardiovascular oscillations represent the integrated control of a system through both autonomic branches by systemic haemodynamic changes within a fluid‐filled, physical system. However, our current precise measurement of short‐term cardiovascular fluctuations does not necessarily mean we have an adequate understanding of them. Empirical observation suggests that both respiratory and Mayer wave fluctuations derive from mutable autonomic and haemodynamic inputs. Evidence strongly suggests that respiratory sinus arrhythmia both contributes to and buffers respiratory arterial pressure fluctuations. Moreover, even though virtual abolition of all R‐R interval variability by cholinergic blockade suggests that parasympathetic stimulation is essential for expression of these variabilities, respiratory sinus arrhythmia does not always reflect a purely vagal phenomenon. The arterial baroreflex has been cited as the mechanism for both respiratory and Mayer wave frequency fluctuations. However, data suggest that both cardiac vagal and vascular sympathetic fluctuations at these frequencies are independent of baroreflex mechanisms and, in fact, contribute to pressure fluctuations. Results from cardiovascular modelling can suggest possible sources for these rhythms. For example, modelling originally suggested low frequency cardiovascular rhythms derived from intrinsic delays in baroreceptor control, and experimental evidence subsequently corroborated this possibility. However, the complex stochastic relations between and variabilities in these rhythms indicate no single mechanism is responsible. If future study of cardiovascular variabilities is to move beyond qualitative suggestions of determinants to quantitative elucidation of critical physical mechanisms, both experimental design and model construction will have to be more trenchant.

Spontaneous Indices Are Inconsistent With Arterial Baroreflex Gain

Abstract—Spontaneously occurring, parallel fluctuations in arterial pressure and heart period are frequently used as indices of baroreflex function. Despite the convenience of spontaneous indices, their relation to the arterial baroreflex remains unclear. Therefore, in 97 volunteers, we derived 5 proposed indices (sequence method, &agr;-index, transfer function, low-frequency transfer function, and impulse response function), compared them with arterial baroreflex gain (by the modified Oxford pharmacologic technique), and examined their relation to carotid distensibility and respiratory sinus arrhythmia. The subjects comprised men and women (n=41) aged 25 to 86 years, 30% of whom had established coronary artery disease. Generally, the indices were correlated with each other (except &agr;-index and low-frequency transfer function) and with baroreflex gain. However, the Bland-Altman method demonstrated that the spontaneous indices had limits of agreement as large as the baroreflex gain itself. Even in individuals within the lowest tertile of baroreflex gain for whom baroreflex gain appears to be the most clinically relevant, spontaneous indices failed to relate to baroreflex gain. In fact, for these individuals, there was no correlation between any index and baroreflex gain. Forward stepwise linear regression showed that all spontaneous indices and baroreflex gain were related to respiratory sinus arrhythmia, but only baroreflex gain was related to carotid distensibility. Therefore, these data suggest that spontaneous indices are inadequate estimates of gain and are inconsistent with arterial baroreflex function.

Controlled breathing protocols probe human autonomic cardiovascular rhythms

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (∼0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing ( P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2modestly ( P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men?

Background—We measured cardiovagal baroreflex gain and its vascular mechanical and neural components during dynamic baroreflex engagement in 10 young untrained men, 6 older untrained men, and 12 older, physically active men. Methods and Results—Our newly developed assessment of beat-to-beat carotid diameters during baroreflex engagement estimates the mechanical transduction of pressure into barosensory stretch (&Dgr;diameter/&Dgr;pressure), the neural transduction of stretch into vagal outflow (&Dgr;R-R interval/&Dgr;diameter), and conventional integrated cardiovagal baroreflex gain (&Dgr;R-R interval/&Dgr;pressure). Integrated gain was lower in older untrained men than in young untrained men (6.8±1.2 versus 15.7±1.8 ms/mm Hg) due to both lower mechanical (9.1±1.0 versus 17.1±2.4 mm Hg/&mgr;m) and lower neural (0.57±0.10 versus 0.90±0.10 ms/&mgr;m) transduction. Integrated gain in older active men (13.3±2.7 ms/mm Hg) was comparable to that in young untrained men. This was achieved through mechanical transduction (12.1±1.4 mm Hg/&mgr;m) that was modestly higher than that in older untrained men and neural transduction (1.00±0.20 ms/&mgr;m) comparable to that in young untrained men. Across groups, both mechanical and neural components were related to integrated gain; however, the neural component carried greater predictive weight (&bgr;=0.789 versus 0.588). Conclusions—Both vascular and neural deficits contribute to age-related declines in cardiovagal baroreflex gain; however, long-term physical activity attenuates this decline by maintaining neural vagal control.

Sympathetic Control of the Cerebral Vasculature in Humans

Background and Purpose— The role of the sympathetic nervous system in cerebral autoregulation remains poorly characterized. We examined cerebral blood flow responses to augmented arterial pressure oscillations with and without sympathetic blockade and compared them with responses in the forearm circulation. Methods— An oscillatory lower body negative pressure of 40 mm Hg was used at 6 frequencies from 0.03 to 0.08 Hz in 11 healthy subjects with and without &agr;-adrenergic blockade by phentolamine. Results— Sympathetic blockade resulted in unchanged mean pressure and cerebral flow. The transfer function relationship to arterial pressure at frequencies >0.05 Hz was significantly increased in both the cerebral and brachial circulations, but the coherence of the relation remained weak at the lowest frequencies in the cerebral circulation. Conclusion— Our data demonstrate a strong, frequency-dependent role for sympathetic regulation of blood flow in both cerebral and brachial circulations. However, marked differences in the response to blockade suggest the control of the cerebral circulation at longer time scales is characterized by important nonlinearities and relies on regulatory mechanisms other than the sympathetic system.

Exercise and aging: autonomic control of the circulation.

This review describes age-related changes in autonomic control of the circulation during exercise and the associated effects on exercise capacity. The increase in heart rate during exercise becomes smaller with aging probably due to both less withdrawal of cardiac vagal tone and diminished beta-adrenergic responsiveness. The latter also appears to contribute to an attenuation in the left ventricular contractile response to exercise despite greater beta-adrenergic stimulation. At rest, muscle sympathetic nerve activity and arterial plasma norepinephrine spillover rates are elevated in older humans. With aging, sympathetically mediated vasoconstriction in nonactive muscle is augmented during brief dynamic exercise. Paradoxically, during more prolonged exercise increases in plasma norepinephrine concentrations/spillover rates are not greater with age. These age-related changes do not adversely affect submaximal exercise performance at a particular % maximal oxygen consumption. However, the lower peak heart rate and attenuated left ventricular contractile response reduce maximal cardiac output, oxygen consumption, and exercise capacity. In older humans, aerobic exercise training lowers heart rate at rest, reduces levels of heart rate and plasma catecholamines at the same absolute submaximal workload, and, at least in men, improves left ventricular performance during peak exercise, but does not reduce, and may even increase, basal sympathetic nerve activity.

Estrogen Replacement Therapy Improves Baroreflex Regulation of Vascular Sympathetic Outflow in Postmenopausal Women

Background—Menopausal estrogen loss has been associated with increased cardiovascular disease in postmenopausal women. However, the link between estrogen and cardiovascular disease remains unclear. Some data suggest estrogen mediates its effect through changes in arterial pressure and its regulation. However, the data available in older women are equivocal regarding estrogen’s ability to reduce resting arterial pressure or to improve its regulation. Methods and Results—We studied 11 healthy, postmenopausal women before and after 6 months of estrogen administration. Arterial pressure was measured by brachial auscultation and finger photoplethysmography. Vascular sympathetic nerve activity was measured in the peroneal nerve by microneurography, and the slope of the relations between changes in heart period, sympathetic activity, and arterial pressure caused by bolus infusions of nitroprusside and phenylephrine were used as an index of baroreflex gain. Estrogen therapy did not change systolic pressure (128±2 versus 123±2 mm Hg) or cardiac-vagal baroreflex gain (6.6±0.9 versus 6.7±0.7 ms/mm Hg). However, vascular sympathetic baroreflex gain was increased (−4.6±0.6 versus −7.4±1.0 arbitrary integrated units/mm Hg;P =0.02). Conclusion—These findings suggest long-term estrogen replacement therapy has effects on cardiovascular regulation that may not be reflected in resting arterial pressures.

Quantification of Mechanical and Neural Components of Vagal Baroreflex in Humans

Abstract—Traditionally, arterial baroreflex control of vagal neural outflow is quantified by heart period responses to falling and/or rising arterial pressures (ms/mm Hg). However, it is arterial pressure-dependent stretch of barosensory vessels that determines afferent baroreceptor responses, which, in turn, generate appropriate efferent cardiac vagal outflow. Thus, mechanical transduction of pressure into barosensory vessel stretch and neural transduction of stretch into vagal outflow are key steps in baroreflex regulation that determine the conventional integrated input-output relation. We developed a novel technique for direct estimation of gain in both mechanical and neural components of integrated cardiac vagal baroreflex control. Concurrent, beat-by-beat measures of arterial pressures (Finapres), carotid diameters (B-mode ultrasonography), and R-R intervals (ECG lead II) were made during bolus vasoactive drug infusions (modified Oxford technique) in 16 healthy humans. The systolic carotid diameter/pressure relationship (r2=0.79±0.008, mean±SEM) provided a gain estimate of dynamic mechanical transduction of pressure into a baroreflex stimulus. The R-R interval/systolic diameter relationship (r2=0.77±0.009) provided a gain estimate of afferent-efferent neural transduction of baroreflex stimulus into a vagal response. Variance between repeated measures for both estimates was no different than that for standard gain (P >0.40). Moreover, in these subjects, the simple product of the 2 estimates almost equaled standard baroreflex gain (ms/mm Hg=0.98x+2.27;r2=0.93, P =0.001). This technique provides reliable information on key baroreflex components not distinguished by standard assessments and gives insight to dynamic mechanical and neural events during acute changes in arterial pressure.

Spectral indices of human cerebral blood flow control: responses to augmented blood pressure oscillations

We set out to fully examine the frequency domain relationship between arterial pressure and cerebral blood flow. Oscillatory lower body negative pressure (OLBNP) was used to create consistent blood pressure oscillations of varying frequency and amplitude to rigorously test for a frequency‐ and/or amplitude‐dependent relationship between arterial pressure and cerebral flow. We also examined the predictions from OLBNP data for the cerebral flow response to the stepwise drop in pressure subsequent to deflation of ischaemic thigh cuffs. We measured spectral powers, cross‐spectral coherence, and transfer function gains and phases in arterial pressure and cerebral flow during three amplitudes (0, 20, and 40 mmHg) and three frequencies (0.10, 0.05, and 0.03 Hz) of OLBNP in nine healthy young volunteers. Pressure fluctuations were directly related to OLBNP amplitude and inversely to OLBNP frequency. Although cerebral flow oscillations were increased, they did not demonstrate the same frequency dependence seen in pressure oscillations. The overall pattern of the pressure–flow relation was of decreasing coherence and gain and increasing phase with decreasing frequency, characteristic of a high‐pass filter. Coherence between pressure and flow was increased at all frequencies by OLBNP, but was still significantly lower at frequencies below 0.07 Hz despite the augmented pressure input. In addition, predictions of thigh cuff data from spectral estimates were extremely inconsistent and highly variable, suggesting that cerebral autoregulation is a frequency‐dependent mechanism that may not be fully characterized by linear methods.

COMPARISON OF B-MODE, M-MODE AND ECHO-TRACKING METHODS FOR MEASUREMENT OF THE ARTERIAL DISTENSION WAVEFORM

Measurements of arterial diameter throughout the cardiac cycle (i.e., the arterial distension waveform) are conducted increasingly to study mechanical properties of the arterial wall and changes associated with disease. The distension waveform of peripheral arteries can be measured noninvasively via ultrasonic echo tracking. M-mode imaging, and B-mode imaging. Of these, echo tracking is the most popular method because of its single micrometer resolution during continuous measurements under ideal conditions. However, high resolution within continuous measurements does not imply high reproducibility between measurements. Therefore, we compared repeated measurements of the amplitude of common carotid artery distension in 26 subjects, obtained sequentially in random order by: 1. Off-line echo tracking of digitized radiofrequency ultrasound; 2. M-mode imaging with automated edge detection; and 3. 30-Hz B-mode imaging with automated edge detection and model-based diameter estimation. In each case, the transducer was hand-held and was removed from the neck between repeated measurements. The amplitude of arterial distension was estimated from the serial diameter measurements by maximum likelihood (ML) estimation, by least-squares fit of a Fourier series model, and by application of a cubic smoothing spline. Within continuous measurements, the standard deviation of the ML distension amplitude for neighboring cardiac cycles was significantly smaller (p > 0.05) with echo-tracking (0.023 mm) than with the B-mode (0.036 mm) or M-mode (0.074 mm) methods. However, between discontinuous measurements on the same subject, the standard deviation of the ML distension amplitude was similar for the echo-tracking (0.076 mm) and B-mode (0.073 mm) methods. The Fourier series model and the cubic smoothing spline slightly reduced the standard deviation of the B-mode and M-mode distension amplitudes, but also reduced the mean amplitude estimate. On the basis of this relative comparison of methods, we conclude that, although echo tracking offers high resolution for continuous measurements, the reproducibility of discontinuous measurements of carotid artery distension is no better with echo tracking than can be obtained from 30-Hz B-mode images.