Arterial Blood Pressure Oscillations Research Articles

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis.

Standard autonomic tests [heart rate response to deep breathing (HRDB), change in systolic blood pressure due to tilt], and spectral analysis of heart rate (HR), arterial blood pressure (ABP), and the associated transfer function analysis (gains and phases) were performed in 20 patients with multiple sclerosis to determine their diagnostic value. Transfer function analysis suggested impairment of baroreflex function in 7 patients and an alteration of cardiorespiratory coupling on a brain stem level in 4 patients. In addition, sympathetic vasomotor outflow was reduced in 2 patients (spectral ABP measures in the mid frequency band) and a decrease of vagal outflow was suggested by abnormal respiratory HR parameters in another 2 patients. An abnormal HRDB was present in 5 patients and was probably due to a central alteration (cardiorespiratory coupling) in 2 patients and due to diminished respiratory effort in 1 patient. Spectral analysis of both HR and ABP oscillations and their transfer function may considerably improve the pathophysiological interpretation of cardiovascular autonomic dysfunction in patients with central nervous system disease.

Very low frequency oscillations in arterial blood pressure after autonomic blockade in conscious dogs.

The aim of this study was to investigate spontaneous variability of arterial blood pressure in conscious foxhounds in the absence of direct sympathetic and parasympathetic influences. Autonomic blockade was achieved by administration of the ganglionic blocking agent hexamethonium (n = 7). In contrast to the control group (n = 7), marked oscillations with a cycle length of 100 s (0.01 Hz) were observed. The relationship of the power densities of the oscillation band (0.01 +/- 0.005 Hz) to the total power increased threefold (0.213 +/- 0.007 vs. 0.057 +/- 0.005; P < 0.01). The 0.01-Hz oscillations typically commenced after some delay. To test whether the absence of the mechanoreceptor afferents was responsible for these fluctuations, we investigated an additional group of foxhounds that were subjected to total baroreceptor and cardiopulmonary receptor denervation (n = 7). Neither in this protocol, nor in a group subjected to denervation and ganglionic blockade (n = 6), did we observe sustained oscillations in this frequency range. Since the oscillations were not seen after combined afferent (mechanoreceptor denervation) and efferent (ganglionic) blockade, central oscillators as a source of the oscillations can be ruled out. A simple model of a circulating pressoric factor may explain the fluctuations, provided that there is a time delay between the stimulus and the release or action of the factor. The findings suggest that a circulating factor accounts for the 0.01-Hz oscillations, which is dependent on intact pathways from the cardiac receptors or baroreceptors to the central nervous system. This hypothesis is put forward since cardiopulmonary and baroreceptor denervation blocked the oscillations seen after ganglionic blockade.

Baroreflex sensitivity assessed by complex demodulation of cardiovascular variability.

We used complex demodulation of cardiac interval and systolic arterial blood pressure oscillations in the low-frequency band (0.04 to 0.14 Hz) to investigate baroreceptor control of heart rate. Baroreflex sensitivity was defined as the instantaneous amplitude of complex-demodulated oscillations in the RR interval divided by the instantaneous amplitude of complex-demodulated oscillations in systolic blood pressure. We evaluated the method using both simulated and actual data obtained from 33 healthy nonsmokers during supine and standing postures. To test the validity and reliability of the method, we compared the mean values of baroreflex sensitivity calculated using complex demodulation with the values obtained using power spectral analysis and sequential analysis of spontaneous variations in blood pressure and RR interval. All three methods applied to the simulated data yielded the same values of baroreceptor sensitivity. Mean values of baroreflex sensitivity assessed by complex demodulation of the actual data were similar to those calculated by both power spectral analysis and sequential analysis (13.9 +/- 5.2 versus 13.7 +/- 6.7 or 14.3 +/- 6.5 ms/mm Hg for supine and 7.3 +/- 2.8 versus 7.0 +/- 3.0 or 7.2 +/- 2.8 ms/mm Hg for standing, respectively). In addition, a significant correlation existed between the values obtained by complex demodulation and power spectral analysis (r = .97, P = .0001) and sequential analysis (r = .98, P = .0001). Furthermore, complex demodulation-derived baroreflex sensitivity fluctuated across time during both the supine and standing postures, and this could not be discerned by power spectral analysis. The results indicate that complex demodulation provides a dynamic assessment of baroreflex sensitivity and may be a useful tool in exploring reflex autonomic control of the cardiovascular system.

Phase relation of cerebral and skin B- and M-waves to arterial blood pressure oscillations P. Zunker, R.R. Diehl, R. Baron, H.-J. H�bler, A. Allardt, G. Deuschl. Departments of Neurology, Kiel University Hospital, Kiel; Alfried Krupp Hospital, Essen, Germany

Phase relation of cerebral and skin B- and M-waves to arterial blood pressure oscillations P. Zunker, R.R. Diehl, R. Baron, H.-J. H�bler, A. Allardt, G. Deuschl. Departments of Neurology, Kiel University Hospital, Kiel; Alfried Krupp Hospital, Essen, Germany

Phase relation of cerebral and skin B- and M-waves to arterial blood pressure oscillations: P. Zunker, R.R. Diehl, R. Baron, H.-J. Ha¨bler, A. Allardt, G. Deuschl. Departments of Neurology, Kiel University Hospital, Kiel; Alfried Krupp Hospital, Essen, Germany

Phase relation of cerebral and skin B- and M-waves to arterial blood pressure oscillations: P. Zunker, R.R. Diehl, R. Baron, H.-J. Ha¨bler, A. Allardt, G. Deuschl. Departments of Neurology, Kiel University Hospital, Kiel; Alfried Krupp Hospital, Essen, Germany

Role of cardiac output in mediating arterial blood pressure oscillations.

The objective of this study was to determine the role of cardiac output in mediating spontaneous fluctuations in mean arterial pressure (MAP) conscious dogs. Dogs were chronically instrumented to monitor MAP and cardiac output. Atrioventricular (AV) block was induced, and left ventricular and right atrial electrodes were implanted. After recovery, MAP was observed for 5 min under two conditions: 1) normal variation in heart rate and cardiac output via triggering the ventricular stimulator with each atrial depolarization (effectively reversing the AV block, AV-linked stimulation) and 2) computer control of ventricular rate to maintain cardiac output constant on a by-beat basis at the same level as observed during normal variations in heart rate and cardiac output. When cardiac output was held constant, large-amplitude, low-frequency oscillations in MAP were readily apparent. Spectral analysis by fast Fourier transform revealed that during constant cardiac output the power observed at low frequencies in the MAP spectrum represented 95.0 +/- 2.7% of the total power compared with 75.5 +/- 4.6% during normal variations in heart rate and cardiac output (P < 0.05). In addition, when cardiac output was held constant, the power observed at higher frequencies markedly decreased from 24.5 +/- 4.6% of total power during AV-linked stimulation to only 5.0 +/- 2.7% of total power during constant cardiac output (P < 0.05). We conclude that low-frequency oscillations in MAP are due to changes in peripheral resistance, whereas a significant amount of high-frequency changes in MAP stems from spontaneous changes in cardiac output.

Spectral analysis of arterial blood pressure and raphe magnus neuronal activity in anesthetized rats.

Recent evidence suggests that nociceptive modulatory cells in the nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC) may participate in the modulation of autonomic processing. Therefore, spectral analyses were used to determine component frequencies common to both arterial blood pressure and the activity of RM/NRMC neurons in rats lightly anesthetized with isoflurane. These analyses detected powerful, extremely low frequency (period length: 6.4-18.5 min) oscillations in arterial blood pressure and in the activity of two classes of RM/NRMC neurons, ON and OFF cells. All ON cells discharged during periods of low blood pressure, whereas all OFF cells discharged during periods of high blood pressure. In contrast, the discharge of NEUTRAL and REGULAR cells did not have a consistent relationship to blood pressure. The role of these cells in nociceptive modulation is also unclear. The results presented indicate that ON and OFF cells may participate in the modulation of both autonomic and nociceptive processing.

Insight into blood-pressure control in SHR via the response to acute hemorrhage: a spectral analysis approach

In this study we investigated, by means of the spectral analysis approach, the possible alterations in the activity of the pressor-control mechanisms in relation to the development of essential hypertension. Since the maintenance of controlled arterial blood pressure (ABP) levels is achieved by a continuously fluctuating control system, instantaneous ABP varies continuously in direct correlation with the activation of various control branches. The power spectrum of ABP fluctuations thus provides a quantitative measure of the activity of the various controlling mechanisms. Two strains of rats, Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto normotensive rats (WKY), were subjected to acute hemorrhage, a procedure known to trigger a strong response, of both the neural (autonomic nervous system) and the hormonal (renin-angiotensin and vasopressin) systems. ABP was continuously recorded from the caudal artery in conscious, 1-month-old SHR and WKY. Three groups of rats were studied. Group 1, acute 2-ml hemorrhage; Groups 2, injection of prazosin (2.5 mg/kg) or Group 3, captopril (4 mg/kg), each followed by bleeding as in the group 1. Spectral analysis of ABP fluctuations was performed on time traces of 20 min duration. The low-frequency part of the power spectrum was analyzed. Three frequency bands were investigated: 0.004–0.04 Hz, 0.04–0.07 Hz and 0.07–0.1 Hz. In SHR, although the baseline mean ABP levels were similar to those of WKY, ABP fluctuations were significantly dampened in SHR in each of the three frequency ranges. Hemorrhage induced, in both strains, a similar fall in mean ABP accompanied by an increase in the slow ABP fluctuations. However, in SHR, the response was significantly greater that that of WKY. The steepest response was observed in the slowest, 0.004–0.04 Hz frequency band, 8.7 ± 1.7 vs. 1.5 ± 0.4 times the baseline levels. However, this intense increase in power after hemorrhage brought the two strains to similar levels. The difference in the response to bleeding was eliminated, in the three frequency ranges, by α 1 blockade. Captopril reduced the response to bleeding in SHR, to the level observed in WKY in all three frequency bands. Spectral analysis of the spontaneous oscillations in ABP unmasks abnormalities which conventional blood pressure measurements cannot detect in 1-month-old, still normotensive SHR. It thus, provides a tool to study the dynamics of the abnormalities which precede the development of hypertension. Bleeding amplifies the malfunction observed in SHR under baseline conditions, since the mean ABP levels were similar in both strains before and after bleeding, SHR seem to retain the ability to respond to a fall in blood volume by requiring a greater recruitment of the control mechanisms than WKY.

Phase relationship between cerebral blood flow velocity and blood pressure. A clinical test of autoregulation.

This study investigates the usefulness, as a test of dynamic autoregulation, of phase shift angle analysis between oscillations in cerebral blood flow velocity (CBFV) and in arterial blood pressure (ABP) during deep breathing. Fifty healthy volunteers, 20 patients with occlusive cerebrovascular diseases (OCD), and 10 patients with arteriovenous malformations (AVM) took part in the study. All subjects received transcranial Doppler monitoring of both middle cerebral arteries (MCAs). In addition, continuous blood pressure monitoring was performed with the use of noninvasive servo-controlled infrared finger plethysmography during deep breathing at a rate of 6/min. With the use of a high-pass filter model of autoregulation, autoregulation was quantified as phase shift angle between oscillations in CBFV and ABP at a frequency of 6/min. A phase shift angle of 0 degrees indicates total absence of autoregulation, while 90 degrees can be gauged as optimal autoregulation. In addition, vasomotor reactivity of both MCAs to CO2 stimulation was assessed among patients and calculated as percent increase in CBFV per millimeter of mercury of increase in CO2. All normal subjects showed positive phase shift angles between CBFV and ABP (mean +/- SD, 70.5 +/- 29.8 degrees). OCD patients presented with significantly decreased phase shift angles for the MCA only on the pathological side (51.7 +/- 35.1 degrees; P < .05). Patients with AVM showed significantly reduced phase shift angles on both the affected side (26.8 +/- 13.5 degrees; P < .001) and the unaffected side (40.6 +/- 26.6 degrees; P < .01). In patients' groups, phase shift angle and vasomotor reactivity correlated significantly (r = .66; P < .001) after results from all MCAs were pooled. Results confirm the high-pass filter model of cerebral autoregulation: Normal subjects showed predicted positive phase shift angles between CBFV and ABP oscillations. Patients with expected autoregulatory disturbances showed significant decreases in phase shift angles. Close correlations existed between autoregulation and CO2-induced vasomotor reactivity.

Surges of muscle sympathetic nerve activity during obstructive apnea are linked to hypoxemia

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.

Power spectral analysis of heart rate and arterial blood pressure oscillation in brain-dead patients

To clarify the mechanism of the slow arterial blood pressure oscillation seen in brain-dead patients, we investigated the frequency of fluctuations in arterial blood pressure and heart rate using power spectral analysis. The electrocardiogram, arterial blood pressure and respiration were recorded simultaneously from 9 brain-dead patients and 8 vegetative patients. Power spectral analysis of these data revealed a very slow fluctuation (0.002–0.01 Hz) in arterial blood pressure in brain-dead patients, the frequency of which was equal to that of the low-frequency spectrum of heart rate, indicating vasomotor sympathetic activity. Neuropathological examinations of the medulla and spinal cords of 4 autopsied brain-dead patients revealed that the spinal cord, ventral and dorsal nerve roots, and the nucleus intermediolateralis of the lateral horn below the level of C3/4 were virtually intact. These findings suggest strongly that the slow oscillation of arterial blood pressure in brain-dead patients originates from the vasomotor tone controlled by spinal sympathetic nerves.

Role of the ventral surface of medulla in the generation of Mayer waves

The regions adjacent to the ventrolateral medullary surface (VMS) play critical roles in the regulation of respiratory and cardiovascular function. Furthermore, these areas seem to be important sites for the integration of afferent inputs from certain sensory organs and the source of excitatory inputs to preganglionic sympathetic and parasympathetic neurons. To determine whether the VMS contributes to the generation of nonrespiratory-related periodic oscillations of arterial blood pressure (Mayer waves), excitatory substances, such as N-methyl-D-aspartate (NMDA), cholinergic agonists, and neuropeptides (substance P, neurokinin A, neurotensin), were applied topically to the intermediate area of VMS in anesthetized cats. In addition, the effects of application of lidocaine and inhibitory substances (benzodiazepines) on Mayer waves were studied. After application of excitatory substances to the VMS, we observed oscillations of arterial blood pressure, recurring with a period of 17.8 +/- 10 (SE) s, which had similar characteristics as the Mayer waves recorded during hypercapnia or hypoxia. In addition, cyclic changes in phrenic nerve activity and tracheal tone occurred with the same periodicity as arterial blood pressure oscillation. Application of lidocaine or benzodiazepines on the intermediate area of the VMS abolished Mayer waves observed during hypercapnia, hypoxia, or application of excitatory substances. These findings show for the first time that the VMS can be considered as one of several synaptic relays involved in the generation of arterial blood pressure oscillation, as well as the cyclic changes in phrenic nerve activity and tracheal smooth muscle tone that occur simultaneously.

Low-frequency oscillations in arterial pressure and heart rate: a simple computer model.

We have previously reported that low-frequency oscillations in arterial blood pressure (ABP) and heart rate (HR) occur when conscious dogs experience severe blood loss. These low-frequency oscillations are generated by enhancement of the sympathetic nervous system and inhibition of the parasympathetic nervous system. We have developed a simple computer model to elucidate those properties critical to the generation of these oscillations. Our model incorporates several important features: 1) arterial baroreceptor feedback loops, which relate ABP to targeted HR and total peripheral resistance (TPR) values; 2) two effector outputs, HR and TPR, which are controlled by the outputs of vagal, beta-adrenergic, and alpha-adrenergic effector mechanisms; 3) a fixed beat-to-beat stroke volume; and 4) a wind-kessel model, which represents the peripheral circulation. Each effector mechanism is modeled as a low-pass filter in series with a delay. The vagal effector mechanism slows the HR after a 100-ms delay and reaches maximal HR at that time. The beta-adrenergic effector mechanism speeds HR after a 2.5-s delay and then increases to maximal HR 7.5 s later. The alpha-adrenergic effector mechanism begins vasoconstriction after a 5-s delay and then reaches maximal contraction 15 s later. Computer simulations of inhibition of the vagal effector mechanism and activation of the adrenergic effector mechanisms elicit low-frequency oscillations in ABP and HR. These oscillations are similar to those observed experimentally in the dog during hemorrhage. We conclude that the slow temporal response of the alpha-adrenergic effector mechanism controlling TPR is the critical element in predicting the observed low-frequency oscillations in ABP and HR.

A non-invasive method for testing neural circulatory control in man.

Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subjects with dystonic symptoms and orthostatic intolerance. Oscillations of thermal gradient in the skin were produced by standardised periodic stimulation of the lower part of the arm with warm and cool water. Vasomotor activity of the skin induced oscillations of arterial blood pressure which were thought to be regulated by sympathetic and parasympathetic heart rate control and by oscillation of the sympathetically controlled peripheral vascular resistance. We tested the method in subjects with cardiovascular symptoms (n = 7) and controls (n = 7). At supine rest, the frequency response of the heart rate variability to the thermal stimulation at frequencies of 0.01, 0.02, 0.03 and 0.1 Hz was significantly different (p = 0.008) between symptomatic subjects and controls. The gain of the heart rate control was increased to 0.03 Hz [-1.3(SEM 0.5) dB v -3.8(0.8) dB, p = 0.068] and decreased at 0.1 Hz [-3.9(1.1) dB v -1.5(0.6) dB, p = 0.076] in the test group compared to the control group. At stimulus frequencies of less than 0.03 Hz the individual overall heart rate variability of the subjects with symptoms stayed below the mean control value, at 60(6) ms v 79(15) ms, p = 0.16. The cutaneous temperature oscillations at the site of stimulation, frequency response of the oscillations of the skin blood flow and respiration to the thermal stimulation, and mean heart rate were similar in the both groups. The results show that this thermal entrainment method quantifies the increased sympathetic and decreased parasympathetic cardiac control of subjects with dystonic symptoms.

Spontaneous oscillations of systemic arterial pressure during cardiopulmonary bypass in man

Extracorporeal blood circulation (ECC) provides a steady flow and minimal pulmonary circulation in the absence of cardiac function. Oscillations of systemic arterial pressure were observed in 70 patients during ECC. At the onset of oscillations the frequency was as a rule 4 cycles per minute but depended on the temperature and showed a positive correlation with it. Correspondingly, the amplitude was about 6 mm Hg and depended on aortic pressure and showed a positive correlation with it. During the cooling phase of ECC the frequency decreased and the amplitude increased. The oscillations were independent of central venous pressure and ventilation. The oscillations disappeared either at the beginning of restitution of cardiac function or with decreasing arterial pressure caused by drug administration or rewarming. Arterial blood pressure oscillations have been described in experimental animals under various conditions but also in conscious man. The mechanisms underlying these oscillations are suggested to be nervous in origin, as is possible also in the present findings.

The rate of arterial blood pressure change as a factor in the hysteresis of the baroreceptor reflex.

We induced sinusoidal arterial blood pressure oscillations in anaesthetized dogs, and measured the resulting reflex changes in cardiac cycle length. The graphs of cardiac cycle length as a function of systolic arterial pressure displayed considerable hysteresis. The extent of the hysteresis and the direction around the loop varied with the frequency of the pressure oscillations. At relatively low frequencies (0.02 and 0.04 Hz) the loops were predominantly anticlockwise, whereas at higher frequencies (0.08 and 0.16 Hz) the loops were mainly clockwise in direction. In a second group of dogs we stimulated the transected vagus nerves with sequential ramp-like increases and decreases in voltage. The graph of the chronotropic response displayed a prominent anticlockwise hysteresis. Hence the anticlockwise hysteresis which was induced reflexly by cyclic oscillations of systemic arterial pressure is at least partly ascribable to an efferent vagal mechanism.

Oscillations in mean arterial blood pressure in conscious dogs.

Oscillations in mean arterial blood pressure in conscious dogs.

Distribution of maximum coronary blood flow in the left ventricular wall of anesthetized dogs.

Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In a group of dogs progressive hemodilution was performed until the diastolic reactive hyperemic response to 10 s occlusion of the circumflex branch disappeared ("optimum" hemodilution). At this degree of hemodilution the distribution of blood flow in the left ventricular free wall was evaluated by measuring tissue activity concentrations of Xe-133 and radioactive microspheres after bolus injection into the aortic root. "Optimum" hemodilution was accompanied by a sixfold increase in systolic coronary flow, a 3-fold increase in diastolic flow and a relative endocardial hypoperfusion. These results indicate that the endocardial blood flow reserve is lower than the epicardial. This conclusion is supported by the influence of spontaneous oscillations of arterial blood pressure (Traube-Hering waves) on systolic and diastolic coronary blood flows before and during "optimum" hemodilution. In another group of dogs maximum coronary vasodilatation was produced by occlusion of the left coronary artery for 10 s. In this group the distribuition of Xe-133 and radioactive microspheres were measured after bolus injection into the aortic root at peak diastolic reactive hyperemia. The epi- and endocardial distribution of both Xe-133 and microspheres was uniform in the left ventricular wall, indicating a uniform flow to these regions. This might be explained by an increased endocardial perfusion during systole due to loss of myocardial contractility or by a decline towards resting level in epicardial flow at the time of injection, corresponding to a shorter duration of the hyperemic period in the epi- than endocardial region.

Sympathetic unit activity associated with Mayer waves in the spinal dog.

Sympathetic unit activity associated with Mayer waves in the spinal dog.

Oscillatory behavior of the sympathetic system induced by picrotoxin.

In cats anesthetized with sodium pentobarbital, paralyzed with gallamine, atropinized, and artificially ventilated, an intravenous injection of picrotoxin (dose between 2 and 5 mg/kg) consistently induced sustained oscillations of arterial blood pressure (BP). Because of their form, and regularity of repetition (range: 0.3 to 4 cycles/min), these oscillations can be considered analogous to vasomotor waves (Mayer waves), which are known to occur in conditions such as hemorrhage, metabolic acidosis, and cerebral ischemia. The BP oscillations characteristic of picrotoxin intoxication have the following properties: (i) they are generated in the CNS since they are abolished by ventral root block; (ii) they are accompanied in most cases by oscillations of the nictitating membrane tension of the same frequency; and (iii) they occur in animals with complete transection of the spinal cord at a cervical level and in those with sectioned ninth and tenth nerves; hence they are not dependent upon afferent impulse traffic arising in baro- and chemo-receptors. Furthermore, nictitating membrane tension oscillation has been seen when BP was maintained stable. The latter observations indicate that for maintaining the oscillation in the sympathetic system the concomitant hemodynamic changes are not essential. It would appear that the oscillation is the result of epileptiform activity of sympathetic neurons. Perhaps some types of spontaneously occurring vasomotor waves have a similar origin.