Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation.

We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P < 0.001), with the decrease being greater after centrifugation only in the GZ group (P < 0.05). PET(CO2) also decreased with HUT in both groups (P < 0.01), but the absolute level of decrease was unaffected by centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P < 0.02). However, these greater decreases were not associated with greater increases in CVR. In the supine position after centrifugation compared with before centrifugation, GAIN increased in both groups (P < 0.05, suggesting an autoregulatory deficit), with the change being correlated to a measure of otolith function (the linear vestibulo-ocular reflex) in the GX group (r = 0.76, P < 0.05) but not in the GZ group (r = 0.24, P = 0.60). However, GAIN was subsequently restored to precentrifugation levels during postcentrifugation HUT (i.e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

Simultaneous transcranial Doppler and arterial blood pressure response to lower body negative pressure.

Microgravity induces fluid shifts which can alter the cardiovascular responses of astronauts both during space flight and on return to Earth. The decrease in orthostatic tolerance in astronauts returning from a weightless environment can be modelled in ground-based studies using lower body negative pressure (LBNP). This study examined the physiological changes induced by LBNP and determined a reliable method of predicting the onset of presyncope to enable evaluation of countermeasures for loss of orthostatic tolerance, such as glycerol-induced hyperhydration. Six healthy male subjects, aged 18 to 45 years, were each subjected to two LBNP tests, with or without glycerol ingestion. Continuous, non-invasive measurements of middle cerebral artery blood flow velocities (CBF) by transcranial Doppler, arterial blood pressure (Finapres ABP), ECG and LBNP box pressures were recorded during each test. Negative pressure was increased in three minute intervals until symptoms of presyncope were observed. An increase in heart rate (HR), a relatively constant mean ABP and a steady decline in mean CBF were consistently observed as the box pressure was decreased. The continuous on-line measurements clearly showed consistent dynamic changes in both CBF and ABP waveforms in response to changes in LBNP. At the onset of presyncope, sudden drops in mean ABP, HR and mean CBF were typically noted, the latter providing the earliest indication of presyncope. The time required to re-establish original baseline values of CBF and ABP after release of box pressure varied widely from six to over ten minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow velocities by transcranial Doppler during parabolic flight.

Microgravity is produced for 20 to 30 seconds in NASA's KC-135 aircraft at the end of a 2 G pullup for each of 40 parabolas per flight. Continuous transcranial Doppler ultrasound, arterial blood pressure, and acceleration levels were recorded for 12 male and 8 female healthy subjects without known cardiovascular or cerebrovascular disease. Recordings were made throughout 10 parabolas per subject in each of the supine, sitting, and standing postures. The data were digitized for off-line analysis using Fast Fourier Transform and other signal processing methods. A phase lag in changes to transcranial Doppler waveforms from the onset of acceleration was more pronounced in the standing position than in the sitting position. There was less of a phase lag in the supine position. These ultrasound changes preceded the more delayed variations in arterial blood pressure. The KC-135 provides a unique short-term environment that allows measurement of the human response to variations in acceleration but limits physiological monitoring of responses to a steady state of microgravity.

Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight.

The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

Quantitative estimation of spectral broadening for the diagnosis of carotid arterial disease: method and in vitro results.

For the quantitative assessment of carotid arterial disease using continuous wave Doppler ultrasound, the choice of an index to describe the degree of spectral broadening is important. It is shown that a spectral broadening index (SBI) given by 100(1 - fmean/fmax) and evaluated over a 25 msec period around peak systole is relatively insensitive to artifacts and has potential for achieving good clinical sensitivity. Furthermore, it can be implemented very simply on a microcomputer for on-line display. A description of a microcomputer based system, together with the results obtained using an in vitro flow model that closely approximates the carotid flow velocity waveform, are presented. Results relating the SBI to the degree of stenosis, recording site, and angle of insonation, are given. In addition, the results obtained with a commercial system that computes SBI based on the power spectrum, are presented for comparison.

Determination of the hemodynamic factors which influence the carotid Doppler spectral broadening.

In the diagnosis of extracranial carotid arterial disease, quantitative measurements from the continuous wave (CW) Doppler spectrum have the potential for detecting stenoses and occlusions. The measurement of maximum peak Doppler frequency at the site of stenosis has been shown to detect severe, but not minor or moderate, stenoses. Diagnosis of minor or moderate stenoses may be possible by assessing the degree of flow disturbance beyond the stenosis. Such flow disturbances cause the Doppler spectrum at peak systole to be broadened, and it has been suggested that the measurement of spectral broadening may be of diagnostic value. This paper describes the results of an in vitro study aimed at determining the hemodynamic factors that influence the severity of the Doppler spectral broadening. The spectral broadening index (SBI) at peak systole, defined as SBI = 1 - Fmean/Fmax, was used to quantify the instantaneous spectrum. In a pulsatile flow in vitro model that produced spectral waveforms virtually identical to those recorded in the human carotid, we observed a direct linear relationship between SBI and the severity of stenosis, at least for those stenoses having greater than 40% cross-sectional area (R = 0.82 to 0.93). The SBI was found to be maximum when recorded immediately beyond the stenosis and returned to normal 4-5 cm downstream from the stenosis. The SBI was higher for nonsymmetrically shaped stenoses than for symmetrical stenoses for lesions greater than 60%, but not for stenoses less than 60%. In this model, the SBI recorded from both normal or abnormal waveforms was not affected by the flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between Doppler pulsatility index and direct femoral pressure measurements in the diagnosis of aortoiliac occlusive disease.

One hundred and seventy-five aortofemoral segments were studied in order to determine the role of CW Doppler ultrasound combined with real-time spectral analysis in the assessment of aortoiliac disease. The pulsatility index (PI), determined from the maximum velocity waveform, was compared to the systolic pressure difference between the aorta and common-femoral artery as measured at the time of angiography. Receiver operating characteristic curves were constructed and the optimum sensitivities and specificities measured. Results show that if a PI(max) of 5.5 is taken as the threshold level, then the PI is 95% sensitive and specific in detecting hemodynamically significant aortoiliac disease that corresponds to a resting aortofemoral pressure difference of 10 mm Hg or greater. We also carefully examine those technical aspects of Doppler recording and analysis that influence the accuracy of PI measurements.

Comparison of CW Doppler ultrasound spectra with the spectra derived from a flow visualization model.

The methods and results of a study to determine the accuracy of continuous wave (CW) Doppler spectral recordings by comparison to the spectra derived from the flow profiles photographed simultaneously in a pulsatile flow visualization model are reported in this paper. A pulsatile pump produced a flow velocity waveform, similar to that seen in the human femoral artery, in a quartz glass tube. The velocity profiles, which were made visible by using a photochromic dye/laser technique, were photographed, and at the same time the instantaneous Doppler spectra were recorded. A comparison of the Doppler data and the photographed profiles gave the following results. The Doppler spectrograms and those reconstructed from the flow visualization data were quite similar. Excellent agreement was observed between the instantaneous maximum and mean Doppler waveforms. Individual spectra showed some differences and these differences were quantified by the novel application of certain statistical shape descriptor coefficients that are based on the estimation of the higher order moments of the spectra. The Doppler spectra are generally more skewed towards higher frequencies, narrower, and more peaked than the flow visualization spectra. Analysis of the assumptions and various sources of error lead to the conclusion that the differences were probably caused by ultrasound beam nonuniformity and the effects of refraction, causing a reduction of the beam field response at the tube edges. It is concluded that provided certain precautions are taken in the measurement technique, the CW Doppler ultrasound spectra fairly accurately represent the true velocity profile.

A critical study of ultrasound Doppler spectral analysis for detecting carotid disease.

The results of in vitro and in vivo studies to determine the application and limitations of frequency analysis for CW Doppler ultrasound assessment of carotid stenoses are reported. In the in vitro study, the peak Doppler frequency and a new spectral broadening index were determined proximal to, at, and distal to axisymmetric and asymmetrical model stenoses. Good correlations with percent area stenoses were found. In the clinical study, 162 cases were examined using a 4 MHz Doppler system and by standard four-vessel arteriography. Peak frequencies of greater than 3.8 KHz were diagnostic of internal carotid stenoses of 3.2 mm minimum lumen diameter or less, with a sensitivity of 92% and a specificity of 94%. Spectral broadening, evaluated by subjective grading, yielded similar results.

In vitro comparison of alternative methods for quantifying the severity of Doppler spectral broadening for the diagnosis of carotid arterial occlusive disease.

Quantitative analysis of continuous wave Doppler recordings is of clinical value in the noninvasive diagnosis of carotid arterial disease. Peak frequency measurements are useful and accurately detect severe stenoses but do not reliably diagnose minor or moderate stenoses because the measurement is dependent upon the probe to vessel angle, which cannot be measured accurately. Recent investigations have focused on efforts to overcome this limitation by quantifying the degree of spectral broadening that occurs as the result of flow disturbances downstream from a stenosis. In this study, an in vitro model was used to determine the optimum method for quantifying the instantaneous Doppler spectrum. The model generates blood flow velocity waveforms that are virtually identical to those found in the human internal carotid artery. Doppler recordings were made from normal tubes and distal to stenoses (39-87% cross-sectional area reduction). The spectra were quantified by the following angle-independent measurements: spectral broadening index and three standard statistical shape descriptors, namely the coefficients of variation, skewedness and kurtosis. Using this model, the results demonstrate an excellent relationship between the severity of the stenosis and each of spectral broadening index (r = 0.99), coefficient of variation (r = 0.96), and coefficient of skewedness (r = 0.99). The calculation of each of the measurements can be implemented quite easily, and a prospective trial is warranted to evaluate their clinical diagnostic accuracy.

Comparative study of four methods for quantifying Doppler ultrasound waveforms from the femoral artery.

Currently, there is no agreement as to the best method for quantifying Doppler ultrasound recordings from peripheral arteries in order to detect occlusive disease. The four methods assessed in this study are: the pulsatility index, height-width index, path length index, and a Laplace transform function index. Recordings of the Doppler ultrasound spectral waveforms from the common femoral artery of 232 limbs were digitized to obtain the maximum velocity waveforms. This data was analyzed and the various indices were computed and then compared with the arteriographic grades. The effect of distal disease was also examined. The diagnostic accuracy of each index was determined from receiver operating characteristics curves. We concluded that all four indices were capable of detecting significant aortoiliac disease with approximately equal diagnostic accuracy of 90-95% but that pulsatility index had the advantages of simplicity and ease of calculation.

An in vitro model and its application for the study of carotid Doppler spectral broadening.

A new in vitro model has been developed for studying the changes in the ultrasound Doppler spectrum that occur in the region of a stenosis. Pulsatile flow in rigid acrylic tubes was produced by means of a modified hemodialysis pump. The Doppler spectral waveforms were measured using a continuous wave Doppler system, a probe of a known field pattern, a real-time high resolution frequency analyzer, and a video display and recording system. The flow velocity waveforms were found to be nearly identical to those seen in the human carotid. Measurements were made to determine the critical stenosis and the results are similar to those reported from in vivo studies. In a preliminary study, the extent of spectral broadening was found to be dependent on the recording site in relation to the stenosis, the severity of the stenosis, and the flow rate. Using qualitative methods it was not possible to determine either the influence of the shape of the stenosis or the phase of the cardiac cycle on spectral broadening.

Development of methods to analyse transcranial Doppler ultrasound signals recorded in microgravity.

During space flights, several clinical syndromes may be the result of changes in cerebral circulation. The purpose of the paper is to describe the development and initial evaluation of a system for recording, processing and displaying transcranial Doppler ultrasound (TCD) waveforms from the middle cerebral artery (MCA) in microgravity. Volunteers were repeatedly subjected to 15-20 s intervals of microgravity ('near zero gravity') during flights on the KC-135 military aircraft. Continuous TCD recordings from the MCA were stored on magnetic tape. The paper describes the system that was developed to digitise the Doppler ultrasound data and markers that corresponded to the various levels of microgravity, obtain the maximum and mean Doppler waveforms, identify the waveforms and quantify them. The results demonstrate the feasibility of making TCD recordings in a microgravity environment and illustrate excellent performance of the system and its ease of operation. Quantitative waveform analysis of the recordings from the first subject studied in the supine position showed statistically significant changes in MCA velocity waveforms during microgravity.

Determination of appropriate clomipramine dosage among depressed African outpatients in Dar es Salaam, Tanzania.

In an open clomipramine dose finding study, 33 depressed indigenous African outpatients were randomly assigned to two regimens of treatment with 125 mg and 75 mg oral medications daily. At the end of eight weeks of treatment, 16 patients (48.5 pc) were on the 75 mg regime, and 17 (54.8 pc) were on 125 mg. Analysis of depression scores on the Beck-Rafaelsen scale indicated improvements of depression in both regimes of equal magnitude. Analysis of variance showed no statistically significant difference on dose response between the two regimes. The higher doses, however, were associated with more drowsiness and tremulousness. It is suggested that Black African patients respond to tricyclic antidepressants in much lower doses than those recommended in Western textbooks. It is also apparent that side effects of tricyclic antidepressants, which have been implicated in non-compliance to medication, could be avoided without compromising treatment outcome.

Management of intracranial meningeal hemangiopericytomas: outcome and experience.

Hemangiopericytomas represent rare intracranial tumors that have a tendency to recur locally and have the unique characteristic of giving extracranial metastases. Our current communication reviews a series of patients diagnosed with hemangiopericytoma who were treated in our facility. Eleven patients with a mean age of 51.2 years underwent follow-up for a mean time of 7.1 years. Their neuroimaging preoperative evaluation included plain skull X-rays, head CT scans, brain MRI, angiograms, and (1)HMRS. Preoperative embolization of the tumor was employed in 6/11 patients. All patients underwent craniotomy for tumor resection and postoperative radiation treatment was employed on all but one. Grade I resection was accomplished in 6/11 (54.5%), grade III in 4/11 (36.4%), and grade IV in 1/11 (9.1%). Local recurrence was detected in 3/11 (27.3%) at a mean period of 5 (range 2-7.5) years. Extracranial metastatic disease was documented in 4/11 (36.4%) patients at a mean of 4.9 (range 2.5-7) years after the initial diagnosis. The GOS score was: 7/11 (63.6%) scored 5, while 4/11 (36.4%) died at a mean time of 5.5 (range 3-8) years after the initial diagnosis. Intracranial hemangiopericytomas management requires aggressive surgical resection, postoperative radiation treatment, and extensive follow-up to rule out local recurrences and delayed extracranial metastases.

An automatic, multi-function pressure cuff control unit.

A fully automatic blood pressure cuff control system is described. The system is designed for use in the assessment of peripheral vascular disease and helps reduce the amount of operator attention required to carry out such measurements properly. It also provides repeatable control of specific functions, thereby eliminating a potential source of variability. The system incorporates a pneumatic control system, an integrated silicon pressure transducer, and a digital readout. The design, modes of operation, safety features, and use of the system are described.

Problems of carotid Doppler scanning which can be overcome by using frequency analysis.

The value of the concomittant use of a real time frequency analyzer along with a continuous wave carotid Doppler scanner is demonstrated in this study of 118 cases. With a colour-coded Doppler scanner alone, internal carotid stenoses greater than 35% were diagnosed with a sensitivity of 95% and a specificity of 82%. With the addition of frequency analysis certain inherent problems with Doppler scanning were overcome and with the measurement of the peak Doppler frequency, the specificity was improved to 93%.

Spectral analysis of Doppler flow velocity signals: assessment of objectives, methods, and interpretation.

The objective of this paper is to review the theoretical basis and clinical application of electrical impedance plethysmography in the noninvasive evaluation of peripheral arterial and venous disease. Theoretical, experimental and clinical studies have not demonstrated a direct relationship between electrical impedance changes and limb volume changes. Potential sources of error have also been identified. This has led to the development of clinical tests based on impedance plethysmography for the detection of peripheral arterial disease, venous insufficiency and venous outflow obstruction. Impedance plethysmography, using the method of venous occlusion, is presently the most commonly employed noninvasive method for the detection of deep venous thrombosis.