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Novak, V.

Publications and source records attributed to Novak, V..

Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome

A variety of approaches have been used to alleviate symptoms in postural tachycardia syndrome (POTS). Drugs reported to be of benefit include midodrine, propranolol, clonidine, and phenobarbital. Other measures used include volume expansion and physical countermaneuvers. These treatments may influence pathophysiologic mechanisms of POTS such as alpha-receptor dysfunction, beta-receptor supersensitivity, venous pooling, and brainstem center dysfunction. The authors prospectively studied hemodynamic indices and symptom scores in patients with POTS who were acutely treated with a variety of interventions. Twenty-one subjects who met the criteria for POTS were studied (20 women, 1 man; mean age, 28.7 +/- 6.8 y; age range, 14-39 y). Patients were studied with a 5-minute head-up tilt protocol, ECG monitoring, and noninvasive beat-to-beat blood pressure monitoring, all before and after the administration of an intervention (intravenous saline, midodrine, propranolol, clonidine, or phenobarbital). The hemodynamic indices studied were heart rate (ECG) and systolic, mean, and diastolic blood pressure. Patients used a balanced verbal scale to record any change in their symptoms between the tilts. Symptom scores improved significantly after the patients received midodrine and saline. Midodrine and propranolol reduced the resting heart rate response to tilt (p <0.005) and the immediate and 5-minute heart rate responses to tilt (p <0.002). Clonidine accentuated the immediate decrease in blood pressure on tilt up (p <0.05). It was concluded that midodrine and intravenous saline are effective in decreasing symptoms on tilt in patients with POTS when given acutely. Effects of treatments on heart rate and blood pressure responses generally reflected the known pharmacologic mechanisms of the agents.

Non-NASA Center↗

Mechanisms of blood pressure alterations in response to the Valsalva maneuver in postural tachycardia syndrome

The postural tachycardia syndrome (POTS) is characterized clinically by orthostatic lightheadedness and tachycardia. When these patients perform a Valsalva maneuver, there is an excessive blood pressure increment after cessation of the maneuver (phase IV) that is sometimes associated with headaches. It is not known whether excessive phase IV is due to excessive peripheral vascular tone (an alpha-adrenergic mechanism) or is a manifestation of increased beta-adrenergic tone (hyperadrenergic state). The authors undertook a pharmacologic study evaluating the effect of intravenous phentolamine (alpha-adrenergic antagonist) and propranolol (beta-adrenergic antagonist) on the different phases of the Valsalva maneuver in a group of patients with POTS and age-matched normal control subjects. Patients with POTS had mean phases, when compared with controls, that were characterized by more negative II_E (p = 0.07), smaller II_L (p = 0.04), and significantly larger phase IV (p = 0.001). The effect of phentolamine was qualitatively and quantitatively different in POTS when compared with controls. Ten mg phentolamine in controls resulted in a significant accentuation of phase II_E (p = 0.001), attenuation of phase II_L (p = 0.002), and increase of phase IV (57.6 vs 30.7 mm Hg; p = 0.025). These changes resembled those of patients with POTS at baseline. In patients with POTS, the phase II abnormalities, already present, were further accentuated (p <0.001), and phase IV became smaller (50.6 vs 73.8 mm Hg; p = 0.09). Propranolol had no significant effect on phases II_E and II_L, but significantly reduced phase IV in both controls (p <0.05) and in patients with POTS (p <0.001) and improved the headache symptoms, when present, during and after phase IV. The authors conclude that phase IV is mainly under beta-adrenergic regulation and that the exaggerated phase IV in POTS is a result of a hyperadrenergic state.

Non-NASA Center↗

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Review↗

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

Non-NASA Center↗

Autoregulation of cerebral blood flow in orthostatic hypotension

BACKGROUND AND PURPOSE: We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). METHODS: We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80 degrees head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO2, total peripheral resistance, and cerebrovascular resistance. RESULTS: All OH patients had lower BP (P<.0001), BFV_diastolic (P<.05), CVR (P<.007), and TPR (P<.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation (R2>.75) but with a flat slope. An expansion of the "autoregulated" range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean deltaBP <40 mm Hg; R2>.75). CONCLUSIONS: The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

Non-NASA Center↗

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension

Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

Non-NASA Center↗

Postural tachycardia syndrome: time frequency mapping

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

NASA Discipline Number 14-10↗

On the maintenance of the Venus nightside ionosphere - Electron precipitation and plasma transport

The relative contributions of electron precipitation and transport of dayside plasma to the maintenance of the Venus nightside ionosphere during the long Venusian night are investigated based on simultaneous Pioneer Venus Orbiter Retarding Potential Analyzer measurements of suprathermal electron fluxes and plasma densities. In about 20 orbits, the nightside integral electron flux of electrons with energies between 5 and 45 eV is observed to be relatively constant in time and altitude, while plasma density is observed to vary by a factor of 10 or more with no correlation with the electron flux. Ionization rates and ion density height profiles are computed for O(+) and O2(+) as a function of magnetic dip angle based on a typical electron spectrum, or a downward flux of O(+) ions. Comparison of the computed profiles with the measured median O(+) and O2(+) density profiles reveals that the measured profiles can only be reproduced by a downward flux of O(+) equal to about 10 to the 8th/sq cm per sec; suprathermal electron energy distributions produce O2(+) and O(+) levels only about half and one tenth those usually observed, respectively. It is thus concluded that transport of O(+) ions from the dayside Venus ionosphere is responsible for approximately 75% of the typical nightside ionization, with variations in O(+) transport mechanism responsible for most of the observed nightside density variations. The remaining ionization is attributed to suprathermal electrons, which contribute principally to the O2(+) peak.

Spenner, K.↗

Observation of the Venus mantle, the boundary region between solar wind and ionosphere

For three orbit paths of the Pioneer Venus orbiter the interaction between the solar wind and the Venusian ionosphere has been studied. Results of the retarding potential analyzer and the magnetometer are described for the boundary region between the solar wind and the planetary ionosphere. These are the first measurements that show that a transition region exists between the two plasmas of different origin. The observed magnetic field and current system producing it appear strong enough to stop the solar wind flow in front of the ionosphere and to separate the shocked solar wind from the ionosphere. The transition region between the ionosheath and the ionosphere is called the 'mantle'. The observed mantle electron energy spectra close to the ionopause show ionospheric character. With increasing height the number of electrons that have ionospheric energies decreases, and the number of electrons that have solar wind energies gradually increases toward the ionosheath boundary, where only solar wind energy spectra are observed. The mantle surrounds the frontside of the ionosphere and extends probably more than eight Venus radii downstream.

Spenner, K.↗

Suprathermal electron energy distribution within the dayside Venus ionosphere

The suprathermal electron energy distribution for the dayside ionosphere has been derived from data returned by the Pioneer-Venus orbiter retarding potential analyzer. The shape and magnitude of the spectrum are consistent with the assumption that solar EUV radiation is the only significant source. The magnitude of the spectrum and its variation with altitude suggest that significant vertical transport occurs, with the electrons being lost through the ionopause. In turn, significant vertical transport suggests that the effective vertical electron heat conductivity may be comparable to the field-free value. The heat input to the thermal electron gas from the measured suprathermal electron flux is too small by a factor of at least five to maintain the observed electron temperature profile if the electron thermal conductivity is assumed to be close to the field-free value. It is thus inferred that most of the heat is supplied by the solar wind.

Knudsen, W. C.↗

Solar zenith angle dependence of ionospheric ion and electron temperatures and density on Venus

The measurements taken during the first year of the Pioneer Venus orbiter retarding potential analyzer indicate the changes of ion and electron temperatures with solar zenith angles. The ion density decreases by an order of magnitude from dayside to nightside; median ion temperatures above 300 km are constant with the solar zenith angle below 150 deg and reach 2300 K at the ionopause. The ion temperatures below 300 km are almost constant with solar zenith angles during the dayside, but increase with the angles on the nightside. The electron temperatures suggest a constant heat flux into the electron gas at the ionopause which may be supplied by dissipation of energy by the whistler mode plasma waves at the ionopause and/or conduction of heat from the ionosheath through the mantle.

Miller, K. L.↗

Transport of ionospheric O/+/ ions across the Venus terminator and implications

Data from the Pioneer Venus orbiter retarding potential analyzer demonstrate that the velocity of ionospheric O(+) ions in the vicinity of the terminator is directed antisunward and radially inward toward the planet in the range of 1-8 km/s. The velocity tends to increase with altitude, and may increase to still larger values just below the ionopause. The Alfven Mach number of the flow is generally greater than 1, indicating that the flow is controlled more by inertial forces than by magnetic forces. The ion Mach number is also greater than one. The flux of O(+) ions across the terminator planetwise is estimated to be equal to the integrated recombination rate of O2(+) on the night side within a factor of 2. Ion transport contributes substantially, and possibly predominantly, to the maintenance of the night side ionosphere.

Knudsen, W. C.↗

Pioneer Venus Orbiter planar retarding potential analyzer plasma experiment

The retarding potential analyzer (RPA) on the Pioneer Venus Orbiter Mission measures most of the thermal plasma parameters within and near the Venusian ionosphere. Parameters include total ion concentration, concentrations of the more abundant ions, ion temperatures, ion drift velocity, electron temperature, and low-energy (0-50 eV) electron distribution function. Several functions not previously used in RPA's were developed and incorporated into this instrument to accomplish these measurements on a spinning spacecraft with a small bit rate. The more significant functions include automatic electrometer ranging with background current compensation; digital, quadratic retarding potential step generation for the ion and low-energy electron scans; a current sampling interval of 2 ms throughout all scans; digital logic inflection point detection and data selection; and automatic ram direction detection.

Knudsen, W. C.↗

Thermal structure and energy influx to the day- and nightside Venus ionosphere

The thermal structure of and energy influx to the dayside and nightside Venus ionosphere are discussed, based on data obtained by the Pioneer Venus spacecraft. Where the dayside ionosphere appears relatively constant in total ion concentration, ion and electron temperatures and ion composition below the ionopause, retarding potential analyzer measurements confirm the presence of strong spatial and temporal variations in nightside ion concentration. Ion temperatures on the nightside above 225 km are found to be larger by a factor of two or more than on the dayside, and comparable to electron temperatures on the day and night sides. Models of dayside and nightside ion temperatures consistent with observations require the heat input of 0.003 erg/sq cm sec and 0.005 erg/sq cm sec, respectively, to the ion gas to raise the ion temperature above that of the neutral gas, presumably by means of Joule heating.

Knudsen, W. C.↗

Retarding potential analyzer for the Pioneer-Venus Orbiter Mission

The retarding potential analyzer on the Pioneer-Venus Orbiter Mission has been designed to measure most of the thermal plasma parameters within and near the Venusian ionosphere. Parameters include total ion concentration, concentrations of the more abundant ions, ion temperatures, ion drift velocity, electron temperature, and low-energy (0-50 eV) electron distribution function. To accomplish these measurements on a spinning vehicle with a small telemetry bit rate, several functions, including decision functions not previously used in RPA's, have been developed and incorporated into this instrument. The more significant functions include automatic electrometer ranging with background current compensation; digital, quadratic retarding potential step generation for the ion and low-energy electron scans; a current sampling interval of 2 ms throughout all scans; digital logic inflection point detection and data selection; and automatic ram direction detection. Extensive numerical simulation and plasma chamber tests have been conducted to verify adequacy of the design for the Pioneer Mission.

Knudsen, W. C.↗

Thermal structure and major ion composition of the Venus ionosphere - First RPA results from Venus orbiter

Pioneer Venus in situ measurements of thermal plasma quantities were obtained by a retarding potential analyzer. Evidence for significant solar wind heating of the ionosphere and indications that the ionosphere is close to diffusive equilibrium are reported. Information on ionopause height, the ionospheric particle pressures at the ionopause, and the measured ratio of ionospheric scale height to ionopause ratio is presented.

Knudsen, W. C.↗