Blood Pressure Oscillations Research Articles

Abstract T P181: Static And Dynamic Cerebral Autoregulation Dissociate In Asymptomatic Carotid Artery Disease

Background: High grade internal carotid artery (ICA) disease can alter cerebral autoregulation and thus increase risk for ischemia. We aimed to differentiate two types of autoregulation - dynamic cerebral autoregulation (DCA), thought to be a homeostatic process, and vasomotor reactivity (VMR), which determines cerebrovascular reserve - in patients with asymptomatic ICA stenosis. Methods: Twenty-two patients (age 50-93, 16M) with unilateral 80-100% ICA occlusion but no stroke underwent quantitative CBF measurements using continuous arterial spin labeling (CASL) MRI. DCA was performed by continuous insonation of both middle cerebral arteries with transcranial Doppler for 10 minutes at depth 56mm using a standard head frame. Phase shift (PS) between spontaneous oscillations in blood pressure (measured with finger photoplethysmography (Finapres)) and MCA mean flow velocities (MFV) at frequencies .06-.12 Hz was calculated for each hemisphere using transfer function analysis. Lower degree of PS indicated worse autoregulation (abnormal <24deg1). VMR was determined as a response to 2 minutes of 5% CO2 inhalation (abnormal <2% rise in MCA MFV per mmHg PCO2 by Doppler-integrated inline capnometer (Spencer Technologies)). T-test Chi-square, and multivariable linear regression were used to look for associations between VMR, DCA, and hemispheral CBF (SPSS v.22). Results: MCA MFV (p<.001), VMR (p=.002), and CBF (p<.003), were lower in the ICA occlusion hemisphere. DCA difference approached significance (p=0.064). Controlling for age and anterior circle of Willis collateral cross-filling, DCA (p=0.024), but not VMR (p=0.079) on the occluded side was associated with greater hemispheral CBF asymmetry (F=6.87, p=0.024). VMR and DCA were not correlated (Fisher exact =.61). Conclusions: DCA but not VMR correlated with a low flow state produced by high grade ICA disease in asymptomatic patients. Our results suggest that in ICA stenosis dynamic/homeostatic mechanisms may be affected without substantially altering the static/protective mechanism of cerebrovascular reserve. Ongoing studies will investigate the effect of these two autoregulatory mechanisms on vascular cognitive impairment. 1 Ortega-Gutierrez S, et al. J Neuroimaging. 2014 24:379-86

Cerebral autoregulation index at high altitude assessed by thigh-cuff and transfer function analysis techniques.

What is the central question of this study? Whether cerebral autoregulation (CA) is impaired at high altitude and associated with acute mountain sickness remains controversial. We sought to compare two of the most common methods to assess dynamic CA in subjects who ascended to 3424 m and acclimatized. What is the main finding and its importance? We found that CA was reduced at 3424 m when assessed by the classic thigh-cuff inflation-deflation technique, but not when evaluated by transfer function analysis. These findings suggest that the cerebral vasculature of healthy individuals may become less able to buffer a large, abrupt drop in arterial blood pressure, while still maintaining the ability to regulate slow rhythmical oscillations, during periods of moderate hypoxaemia. The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are controversial and confounded by differences in methods used to assess CA. To compare two of the most common methods of dynamic CA assessment, we studied 11 young, healthy sea-level residents (six females and five males; 20.5 ± 2.3 years old) as they ascended to 3424 m and acclimatized over 13 days. A common autoregulation index (ARI) was calculated from the following: (i) transfer function analysis (TFA ARI) of resting oscillations in arterial blood pressure (ABP; finger plethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler); and (ii) MCAv responses following large, abrupt reductions in ABP using the classic thigh-cuff technique (Cuff ARI). Symptoms of acute mountain sickness (AMS) were monitored using the Lake Louise AMS Questionnaire. Cuff ARI scores decreased (P = 0.021) as subjects ascended from low (4.7 ± 1.5) to high altitude (3.2 ± 1.6) and did not change after 13 days of acclimatization (2.9 ± 1.3). The TFA ARI scores were not affected by ascent or acclimatization to 3424 m. Neither Cuff nor TFA ARI scores were correlated with AMS symptoms. These findings suggest that the cerebral vasculature of healthy individuals may become less able to buffer large step changes in ABP, while still maintaining the ability to regulate slow rhythmical oscillations, during periods of moderate hypoxaemia. Given the inherent differences in the autoregulatory stimulus between methods, multiple assessment techniques may be needed to clarify the implications of changes in cerebrovascular regulation at high altitude.

Cardiovascular variability is similarly altered in coronary patients with normal left ventricular function and in heart failure patients.

After myocardial infarction (MI), baroreflex function is impaired and heart rate (HR) variability is reduced. An impaired baroreflex has been observed also in coronary patients with no previous MI, leading to hypothesize alterations of HR variability also in these patients. The aim of the present work was, therefore, to study whether and to what extent cardiovascular variability is altered in coronary patients with no previous MI. Thirty-two individuals were studied: eleven patients with coronary artery disease but no previous MI [coronary artery disease (CAD)], eleven patients with a reduced left ventricular ejection fraction [congestive heart failure (CHF)] and ten age-matched controls (CNT). Overall HR variability was significantly and similarly reduced in CAD (630 ± 272 ms) and CHF patients (594 ± 395 ms) with respect to CNT (1405 ± 837 ms), this being the case also for the low and high frequency spectral components. Low-frequency oscillations of blood pressure (BP) were also significantly and similarly less pronounced in CAD (0.7 ± 0.7 mmHg) and CHF patients (0.7 ± 0.7 mmHg) compared with CNT (1.8 ± 1.4 mmHg). Moreover, both CAD and CHF patients showed a significantly reduced baroreflex function and an increased pulse-wave velocity with respect to CNT. Our study shows that in coronary patients with no MI and no left ventricular dysfunction, there is a profound alteration of both HR and BP variability as in CHF patients, presumably because of a marked impairment of the autonomic modulation of the heart and blood vessels.

Oscillatory behavior of ventricular action potential duration in heart failure patients at respiratory rate and low frequency.

Oscillations of arterial pressure occur spontaneously at a frequency of approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve activity (“Mayer waves”). This study investigated the extent to which corresponding oscillations may occur in ventricular action potential duration (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular pacing devices were studied while seated upright watching movie clips to maintain arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were obtained from unipolar electrograms recorded from the LV epicardial pacing lead during steady state RV pacing from the device. Arterial blood pressure was measured non-invasively (Finapress) and respiration monitored. Oscillations were quantified using time frequency and coherence analysis. Oscillatory behavior of ARI at the respiratory frequency was observed in all subjects. The magnitude of the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis showed a correlation with respiratory oscillation for an average of 43% of the recording time at a significance level of p < 0.05. Oscillations in systolic blood pressure in the Mayer wave frequency range were observed in all subjects for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2 ms. Coherence with Mayer waves at the p < 0.05 significance level was present for an average of 29% of the recording time. In ambulatory patients with heart failure during enhanced mental arousal, left ventricular epicardial APD (ARI) oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz). These findings may be important in understanding sympathetic activity-related arrhythmogenesis.

Spatial mapping of dynamic cerebral autoregulation by multichannel near-infrared spectroscopy in high-grade carotid artery disease.

The exact spatial distribution of impaired cerebral autoregulation in carotid artery disease is unknown. In this pilot study, we present a new approach of multichannel near-infrared spectroscopy (mcNIRS) for non-invasive spatial mapping of dynamic autoregulation in carotid artery disease. In 15 patients with unilateral severe carotid artery stenosis or occlusion, cortical hemodynamics in the bilateral frontal cortex were assessed from changes in oxyhemoglobin concentration using 52-channel NIRS (spatial resolution ∼2 cm). Dynamic autoregulation was graded by the phase shift between respiratory-induced 0.1 Hz oscillations of blood pressure and oxyhemoglobin. Ten of 15 patients showed regular phase values in the expected (patho) physiological range.Five patients had clearly outlying irregular phase values mostly due to artifacts. In patients with a regular phase pattern, a significant side-to-side difference of dynamic autoregulation was observed for the cortical border zone area between the middle and anterior cerebral artery (p < 0.05). In conclusion, dynamic cerebral autoregulation can be spatially assessed from slow hemodynamic oscillations with mcNIRS. In high-grade carotid artery disease,cortical dynamic autoregulation is affected mostly in the vascular border zone. Spatial mapping of dynamic autoregulation may serve as a powerful tool for identifying brain regions at specific risks for hemodynamic infarction.

Special Considerations for Exercise Testing and Programming for Individuals With Spinal Cord Injury

Special Considerations for Exercise Testing and Programming for Individuals With Spinal Cord Injury

Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure–flow relation: The CARNet study

Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann–Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures.These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.

Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat.

Sinusoidal galvanic vestibular stimulation (sGVS) induces oscillations in blood pressure (BP) and heart rate (HR), i.e., vasovagal oscillations, as well as transient decreases in BP and HR, i.e., vasovagal responses, in isoflurane-anesthetized rats. We determined the characteristics of the vasovagal oscillations, assessed their role in the generation of vasovagal responses, and determined whether they could be induced by monaural as well as by binaural sGVS and by oscillation in pitch. Wavelet analyses were used to determine the power distributions of the waveforms. Monaural and binaural sGVS and pitch generated vasovagal oscillations at the frequency and at twice the frequency of stimulation. Vasovagal oscillations and vasovagal responses were maximally induced at low stimulus frequencies (0.025–0.05 Hz). The oscillations were attenuated and the responses were rarely induced at higher stimulus frequencies. Vasovagal oscillations could occur without induction of vasovagal responses, but vasovagal responses were always associated with a vasovagal oscillation. We posit that the vasovagal oscillations originate in a low frequency band that, when appropriately activated by strong sympathetic stimulation, can generate vasovagal oscillations as a precursor for vasovagal responses and syncope. We further suggest that the activity responsible for the vasovagal oscillations arises in low frequency, otolith neurons with orientation vectors close to the vertical axis of the head. These neurons are likely to provide critical input to the vestibulo-sympathetic reflex to increase BP and HR upon changes in head position relative to gravity, and to contribute to the production of vasovagal oscillations and vasovagal responses and syncope when the baroreflex is inactivated.

Relationship of Heart Rate Variability to Sleepiness in Patients with Obstructive Sleep Apnea with and without Heart Failure

Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Wavelet coherence analysis of spontaneous oscillations in cerebral tissue oxyhemoglobin concentrations and arterial blood pressure in elderly subjects

This study aims to assess the relationship between spontaneous oscillations in changes in cerebral tissue oxyhemoglobin concentrations (Delta [HbO2]) and arterial blood pressure (ABP) signals in healthy elderly subjects during the resting state using wavelet coherence analysis. Continuous recordings of near-infrared spectroscopy (NIRS) and ABP signals were obtained from simultaneous measurements in 33 healthy elderly subjects (age: 70.7±7.9years) and 27 young subjects (age: 25.2±3.7years) during the resting state. The coherence between Delta [HbO2] and ABP oscillations in six frequency intervals (I, 0.4–2Hz; II, 0.15–0.4Hz; III, 0.05–0.15Hz; IV, 0.02–0.05Hz, V, 0.005–0.0095Hz and VI, 0.005–0.0095Hz) was analyzed using wavelet coherence analysis. In elderly subjects, the Delta [HbO2] and ABP oscillations were significantly wavelet coherent in interval I, and wavelet phase coherent in intervals I, II and IV. The wavelet coherence in interval I was significantly higher (p=0.040), in elderly subjects than in young subjects whereas that in interval V significantly lower (p=0.015). In addition, the wavelet phase coherence in interval IV was significantly higher in elderly subjects than in young subjects (p=0.028). The difference in the wavelet coherence of the elderly subjects and the young subjects indicates an altered cerebral autoregulation caused by aging. This study provides new insight into the dynamics of Delta [HbO2] and ABP oscillations and may be useful in identifying the risk for dynamic cerebral autoregulation processes.

Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen-mediated control of blood pressure and cardiovascular autonomic control

1. We have shown previously that long-term oestrogen (E2) replacement lowers blood pressure (BP) and improves cardiovascular autonomic control in ovariectomized (OVX) rats. In the present study, we investigated whether constitutive and/or inducible (i) nitric oxide synthase (NOS) modulate these E2 effects. 2. We evaluated changes in BP, myocardial contractility index (dP/dtmax ) and power spectral indices of haemodynamic variability following selective inhibition of endothelial (e) NOS with N(5)-(1-iminoethyl)-L-ornithine (L-NIO), neuronal (n) NOS with N(ω)-propyl-L-arginine (NPLA) or iNOS with 1400W in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control; OVXC) E2. 3. The OVXE2 rats exhibited: (i) reduced BP and increased dP/dtmax ; (ii) cardiac parasympathetic dominance, as reflected by the reduced low-frequency (LF; 0.25-0.75 Hz)/high-frequency (HF; 0.75-3 Hz) ratio of interbeat intervals (IBI(LF/HF)); and (iii) reduced LF oscillations of systolic BP, suggesting a reduced vasomotor sympathetic tone. Inhibition of eNOS (L-NIO; 20 mg/kg, i.p.) elicited a shorter-lived pressor response in OVXE2 than OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). Treatment with 1 mg/kg, i.p., NPLA reduced BP and increased the IBI(LF/HF) ratio in OVXE2 but not OVXC rats. The iNOS inhibitor 1400W (5 mg/kg, i.p.) caused no haemodynamic changes in OVXC or OVXE2 rats. 4. Overall, constitutive NOS isoforms exert restraining tonic modulatory BP effects that encompass eNOS-mediated reductions and nNOS-mediated elevations in BP in OVXE2 rats. Baroreflex facilitation and dP/dtmax reductions may account for the shorter pressor action of L-NIO in E2-treated, compared with untreated, OVX rats.

Entrainment of spontaneous cerebral hemodynamic oscillations to behavioral responses

Entrainment in physiological systems can be manifest in cases where phase-coupling (synchronization) between slow intrinsic oscillations and periodic motor responses, or vice versa, takes place. To test whether voluntary movement has something in common with entrainment of slow hemodynamic oscillations to motor responses, we studied blood pressure (BP), heart rate beat-to-beat intervals (RRI) and prefrontal (de)oxyhemoglobin (Hb/HbO2) during 5min of rest, 10min of self-paced, voluntary movements and 10min of stimulus-paced movements at 10s intervals in 9 subjects. Subjects were divided into 2 groups according to the timing of voluntary finger movements. It appeared that these movements occurred at relatively regular intervals of approximately 10s in 5 subjects (group A); while 4 subjects showed random or very short inter-movement intervals (group B).Two remarkable results were obtained: first, the phase coupling (COH2) between BP and RRI showed a significant (p=0.0061) interaction between activity (rest vs. movement) and group (A vs. B), with an increased (p=0.0003) coupling in group A. Second, the COH2 between BP and Hb oscillations showed a significant (p=0.034) interaction between activity and group, with a decreased (p=0.079) coupling in group B.These results suggest that subjects able to initiate self-paced, voluntary movements at relatively regular intervals of ∼10s show an entrainment potential between physiological oscillations and motor responses. This also provides the first evidence that not only physiological oscillations can be entrained to motor responses, but also motor responses (voluntary movements) can be entrained to slow intrinsic oscillations.

Impaired Dynamic Cerebral Autoregulation and Cerebrovascular Reactivity in Middle Cerebral Artery Stenosis

PurposeWe sought to investigate the capacity of cerebral autoregulation and cerebrovascular reactivity (CVR) in patients with middle cerebral artery (MCA) stenosis.MethodsTwenty-one patients with MCA stenosis diagnosed by magnetic resonance angiography and 15 healthy controls were enrolled. Cerebral autoregulation was assessed by autoregulatory parameters (rate of recovery/phase/gain) derived from transfer function from spontaneous oscillations of cerebral blood flow velocity and blood pressure. CVR was tested by a rebreathing maneuver.ResultsRate of recovery, phase and CVR estimated from moderate MCA stenosis (rate of recovery = 17.76±8.21%/s, phase = 26.93±15.67°, and CVR = 1.53±0.84%/mmHg, respectively) were significantly different (p<0.05) from controls (rate of recovery = 39.62±27.99%/s, phase = 55.66±22.10°, and CVR = 2.18±0.80%/mmHg, respectively). Rate of recovery (r = −0.698, p<0.001), phase (r = −0.738, p<0.001)) and CVR (r = −0.690, p<0.001) were all significantly correlated with the degree of stenosis.ConclusionCerebral autoregulation and CVR were impaired in patients with ≥ 50% MCA stenosis. The measures of both hemodynamic properties were inversely correlated with the stenotic degree.

Abstract W P170: Hemodynamic Effects in Carotid Occlusion Using Arterial Spin Labeling and Transcranial Doppler

Background: High grade carotid stenosis produces hemodynamic effects on the brain, but the relationship between cerebral autoregulation, absolute CBF and neurovascular coupling has not been well-delineated. Methods: Twelve subjects (age 74±9, 3F) with unilateral ICA stenosis (80-100% occluded) but no infarct (asymptomatic or TIA only) underwent dynamic cerebral autoregulation (DCA) testing with transcranial Doppler by comparing phase shift (PS) of spontaneous oscillations in blood pressure (measured with finger photoplethysmography (Finapres)) versus MCA flow velocities at frequencies .06-.12 Hz using transfer function analysis, lower degree of PS indicating worse autoregulation.Neurovascular coupling was assessed by amplitude of absolute increase in CBF in bilateral Brodman area (BA) 4 during a bilateral repetitive hand closure task using continuous arterial spin labeling (CASL) MRI. Four activation (ON) periods were averaged and subtracted from 4 rest (OFF) periods. Resting CBF for each hemisphere’s motor cortex was determined by averaging the OFF periods. Results: All subjects showed: 1) hemispheric asymmetry in baseline CBF with the occluded side being on average 25mL/100g*min (+/- 14 mL/100g*min) lower than the unoccluded hemisphere. 2) hemispheric asymmetry in motor activation: unoccluded hemisphere average activation (mean_CBF_ON - mean_CBF_OFF) in BA4 was 23.7mL/100g*min, representing a 21% increase in local CBF due to activation; occluded hemisphere mean activation was 14 mL/100g*min, representing 18% percent increase in local CBF. 3) Hemispheric asymmetry in DCA, PS=33.1 deg ± 31 on the occluded side vs. 43.5 deg±23 on the non-occluded side. Both the hemispheral difference in baseline CBF (impaired flow) and the difference in DCA measurement (impaired autoregulation) were good predictors of the lower activation (neurovascular coupling) on the occluded hemisphere: R 2 = 0.85 and 0.80, respectively. Conclusion: Both impaired resting CBF and impaired cerebral autoregulation appear to contribute to decreased neurovascular coupling in carotid artery occlusive disease, representing a potential mechanism for occult neuronal dysfunction such as mild cognitive impairment in this patient population.

Impaired Cerebral Autoregulation Is Associated With Vasospasm and Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

Cerebral autoregulation may be impaired in the early days after subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationship between cerebral autoregulation and angiographic vasospasm (aVSP) and radiographic delayed cerebral ischemia (DCI) in patients with SAH. Sixty-eight patients (54±13 years) with a diagnosis of nontraumatic SAH were studied. Dynamic cerebral autoregulation was assessed using transfer function analysis (phase and gain) of the spontaneous blood pressure and blood flow velocity oscillations on days 2 to 4 post-SAH. aVSP was diagnosed using a 4-vessel conventional angiogram. DCI was diagnosed from CT. Decision tree models were used to identify optimal cut-off points for clinical and physiological predictors of aVSP and DCI. Multivariate logistic regression models were used to develop and validate a risk scoring tool for each outcome. Sixty-two percent of patients developed aVSP, and 19% developed DCI. Patients with aVSP had higher transfer function gain (1.06±0.33 versus 0.89±0.30; P=0.04) and patients with DCI had lower transfer function phase (17.5±39.6 versus 38.3±18.2; P=0.03) compared with those who did not develop either. Multivariable scoring tools using transfer function gain>0.98 and phase<12.5 were strongly predictive of aVSP (92% positive predictive value; 77% negative predictive value; area under the receiver operating characteristic curve, 0.92) and DCI (80% positive predictive value; 91% negative predictive value; area under the curve, 0.94), respectively. Dynamic cerebral autoregulation is impaired in the early days after SAH. Including autoregulation as part of the initial clinical and radiographic assessment may enhance our ability to identify patients at a high risk for developing secondary complications after SAH.

Extreme Blood Pressure Oscillations in a Patient With a MEN-2a Syndrome

A 21-year-old man presented to our emergency department because of progressive shortness of breath, hemoptysis, and vomiting. At presentation, a shortbreathed, vomiting patient was seen. His blood pressure (BP) was 234/139 mm Hg, pulse rate was 140/min, respiration rate was 24/min, and peripheral oxygen saturation was 87%. Fundoscopic examination revealed bilateral papilledema. An elevated hematocrit of 57% indicated intravascular hypovolemia, whereas a chest xray was compatible with bilateral pulmonary edema. A hypertensive emergency with acute heart failure was diagnosed, and the patient was transferred to the intensive care unit. Systemic and pulmonary artery pressure recordings showed extreme oscillations (Figure 1). The BP oscillations were accompanied by reciprocal changes in heart rate (Figure 1). The oscillations raised the suspicion of a pheochromocytoma, which was confirmed by elevated plasma concentrations of norepinephrine of 13 100 pg/mL (reference, 600 pg/mL) and of epinephrine of 350 pg/mL ( 100 pg/mL), respectively. Abdominal magnetic resonance imaging revealedabilateral adrenal tumor,positive on I-metaiodobenzylguanidine-scintigraphy. Repeated iv 5-mg bolus injections of phentolamine as well as subsequent infusions of sodium nitroprusside and magnesium sulfate only minimally affected the BP oscillations, but oscillations eventually resolved with extensive fluid resuscitation (17 L in 30 h) plus iv administration of the phosphodiesterase inhibitor enoximone. BP fluctuations are a hallmark of pheochromocytoma. These fluctuations are caused by the paradoxical surges of catecholamines into the circulation and vary in duration, amplitude, and occurrence. The BP oscillations in our patient were quite different. BP oscillations with a cycle time of 10 minutes present in our patient have incidentally been reported in pheochromocytoma patients (1–4). Although we cannot exclude the possibility that the oscillations observed in our patient were caused by a surge of cat-

High-Pass Filter Characteristics of the Baroreflex – A Comparison of Frequency Domain and Pharmacological Methods

Pharmacological methods to assess baroreflex sensitivity evoke supra-physiological blood pressure changes whereas computational methods use spontaneous fluctuations of blood pressure. The relationships among the different baroreflex assessment methods are still not fully understood. Although strong advocates for each technique exist, the differences between these methods need further clarification. Understanding the differences between pharmacological and spontaneous baroreflex methods could provide important insight into the baroreflex physiology. We compared the modified Oxford baroreflex gain and the transfer function modulus between spontaneous RR interval and blood pressure fluctuations in 18 healthy subjects (age: 39±10 yrs., BMI: 26±4.9). The transfer function was calculated over the low-frequency range of the RR interval and systolic blood pressure oscillations during random-frequency paced breathing. The average modified Oxford baroreflex gain was lower than the average transfer function modulus (15.7±9.2 ms/mmHg vs. 19.4±10.5 ms/mmHg, P<0.05). The difference between the two baroreflex measures within the individual subjects comprised a systematic difference (relative mean difference: 20.7%) and a random variance (typical error: 3.9 ms/mmHg). The transfer function modulus gradually increased with the frequency within the low-frequency range (LF), on average from 10.4±7.3 ms/mmHg to 21.2±9.8 ms/mmHg across subjects. Narrowing the zone of interest within the LF band produced a decrease in both the systematic difference (relative mean difference: 0.5%) and the random variance (typical error: 2.1 ms/mmHg) between the modified Oxford gain and the transfer function modulus. Our data suggest that the frequency dependent increase in low-frequency transfer function modulus between RR interval and blood pressure fluctuations contributes to both the systematic difference (bias) and the random variance (error) between the pharmacological and transfer function baroreflex measures. This finding suggests that both methodological and physiological factors underlie the observed disagreement between the pharmacological and the transfer function method. Thus both baroreflex measures contribute complementary information and can be considered valid methods for baroreflex sensitivity assessment.

Direct, intraoperative observation of ~ 0.1 Hz hemodynamic oscillations in awake human cortex: Implications for fMRI

An almost sinusoidal, large amplitude ~0.1Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of ‘slow sinusoidal hemodynamic oscillations’ (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked.Here, we report direct observation of large-amplitude, sinusoidal ~0.1Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, indicating that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4days prior to surgery demonstrates that ~0.1Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison.This direct observation of the ‘0.1Hz wave’ in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.

Impaired Cerebrovascular Hemodynamics are Associated with Cerebral White Matter Damage

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.

Synchronization of low-frequency oscillations in the cardiovascular system: Application to medical diagnostics and treatment

We investigate synchronization between the low-frequency oscillations of heart rate and blood pressure having in humans a basic frequency close to 0.1 Hz. A quantitative estimation of this synchronization based on calculation of relative time of phase synchronization of oscillations is proposed. We show that assessment of synchronization between the considered oscillations can be useful for selecting an optimal dose of beta-blocker treatment in patients after acute myocardial infarction. It is found out that low value of synchronization between the low-frequency rhythms in heart rate and blood pressure at the first week after acute myocardial infarction is a sensitive marker of high risk of mortality during the subsequent 5 years.