Quantitative assessment of peripheral arterial obstruction in Raynaud's phenomenon: development of a predictive model of obstructive arterial cross-sectional area and validation with a Doppler blood flow study.

The objective of this study was to develop a method for the analytical assessment of arterial obstruction in conditions of Raynaud's phenomenon capable of providing diagnostic criteria. Numerous attempts have been made to determine and quantify arterial obstruction in terms of Doppler ultrasound measurements of arterial blood velocity. Absent from these methods is a formulation that allows an assessment of arterial obstruction based on the obstructed area as derived from direct measurement. The authors used spectral analysis of velocity signals from a pulsed, range-gated Doppler ultrasonic instrument to make quantitative measurements of arterial blood flow velocity in hands of normal subjects and persons with Raynaud's phenomenon. They measured the peak and mean velocity during the cardiac cycle and the time integral of the velocity signal over the cardiac cycle. These measurements for two distinct hemodynamic states induced by temperature changes allowed them to calculate the fractional change in arterial cross-sectional area produced by the change in temperature through the application of a hydraulic model of digital arterial circulation. They found an equation expressing fractional obstructed area expressed as: dA/A = 2 (dD - taudv - vtau)/(D + vdtau), where D is the time integral of the velocity signal; tau is the blood flow interval, v is the blood velocity; and dD, dtau and dv are the differences in D, tau, and v at two different hemodynamic states produced by two different temperature states. Their findings suggest that over a temperature range of 35 degrees-25 degrees C, normal subjects experience 0.05/ degrees C reduction in cross-sectional area while Raynaud subjects experience a reduction of 5.8%/degrees C. The results, based on findings in 13 subjects, suggest that Doppler ultrasound can differentiate persons with Raynaud's phenomenon from normal subjects. Additionally, the hydraulic model appears to offer the potential of assessing relative stenotic area in other arterial obstructive diseases.

A model of the pulmonary arterial bed in adults and infants.

A microcomputer model based on an equivalent model of the systemic arterial circulation was used to simulate the pulmonary arterial circulation. The elements chosen to represent the physical properties of the pulmonary arterial bed were determined from the characteristic impedances and tme delays in the system. A terminal resistance that provided a reflection coefficient of 0.56 at a heart rate of 75 min-1 was chosen. The model simulated normal values for pressure and blood velocity in the main pulmonary artery and pulmonary capillary bed of adults and newborn infants. The results indicate that the relatively simple physical principles used to explain systemic hemodynamics are equally applicable to the pulmonary arterial circulation.

Interpretation of the HJ interval of the normal ballistocardiogram based on the principle of conservation of momentum and aortic ultrasonic Doppler velocity measurements during left ventricular ejection.

The principle of conservation of momentum and the observation that blood acceleration in the ascending aorta is approximately constant during ventricular ejection was applied to develop a new interpretation of the HI and IJ intervals of the normal ballistocardiogram. The results indicate that the acceleration (A), velocity (V), and displacement (D) of the ballistocardiogram in the HI and IJ phases may be expressed by a set of equations which, when evaluated numerically, give theoretical acceleration, velocity, and displacement curves. The theoretical A, V, and D curves corresponded closely to those observed on the normal ballistocardiogram record during the HJ interval.

A model of the systemic arterial bed showing ventricular-systemic arterial coupling.

A multielement model of the systemic arterial bed was implemented on a microcomputer and was used to simulate the transient response of the arterial circulation to a specific driving function: a linearly increasing left ventricular pressure. The elements (compliances and inductances) that simulate the aorta and its branches are determined by the characteristic impedances and time delays in the arterial system. The simulations of pressure and blood velocity signals found in a previous version of the model were improved by making the delays in the system nonuniform, with slow central and rapid peripheral wave speeds. This reduced the impedance into which the heart has to pump and increased the distal impedance, raising the peripheral diastolic pressures. When the reflection coefficient was decreased as the heart rate was increased, normal pressure and velocity signals could be maintained over a range of heart rates up to 150 min-1. Extrapolating this relationship to a heart rate of 200 min-1 indicated that the reflection coefficient could be zero at that heart rate, giving optimal power transmission through the arterial bed.

Distortion of chest wall and work of diaphragm in preterm infants.

Chest wall distortion is common in infants and is especially visible in preterm infants. It has been suggested that this distortion increases the volume displacement of the diaphragm during inspiration, which may be associated with muscular fatigue and apnea. We studied 10 preterm infants who had no evidence of lung disease, investigating the effect of chest wall distortion on the volume displacement and work of the diaphragm. The volume changes of the respiratory system were partitioned using an inductance plethysmograph. The minute volume displacement and the work of the diaphragm were calculated using the partitioned abdominal volume change and the gastric and esophageal pressures. The paradoxical movement of the chest wall lasted an average of 36% of inspiration. The minute volume displacement of the diaphragm ranged from 72 to 176% of the minute pulmonary ventilation, and diaphragmatic work ranged from 94 to 793% of that performed on the lungs. The amount of chest wall distortion, as reflected by the duration of the paradoxical chest wall movement, the minute volume excursion, or work of the diaphragm, was not related to the mechanical properties of the lungs. This estimated work load may represent a significant expenditure of calories in these infants and may contribute to the development of diaphragmatic fatigue, apnea, and a prolonged need for mechanical ventilation.

Dynamics of chest wall in preterm infants.

The chest wall of the preterm infant has visible paradoxical movement during breathing, because of its greater flexibility than those of older children and adults. We studied the dynamics of the chest wall in 10 preterm infants to describe the interaction of the chest wall volume, as partitioned by the inductance plethysmograph, and the transthoracic and abdominal pressures. There was considerable hysteresis between the chest wall volume and the transthoracic pressure, and it had linear pressure-volume behavior during airway occlusion, late inspiration, and early expiration. The slope of this pressure-volume relationship, or the instantaneous chest wall compliance, averaged 0.89 +/- 0.16 and 0.94 +/- 0.18 ml/cmH2O for the respiratory effort during airway occlusion and early expiration, respectively. The dynamic compliance was considerably greater, averaging 7.8 +/- 2.3 ml/cmH2O. This resistive pressure-volume behavior was not related to the absolute value of or the rate of development of the esophageal or abdominal pressures. This additional degree of freedom of motion of the chest wall suggests that its linkage to the diaphragm is flexible, which provides a braking force for expiration and allows free movement of the diaphragm for breathing movements before birth.

Doppler blood velocity in the pulmonary artery of infants, children, and adults.

A pulsed, range gated, directional, ultrasonic, Doppler blood velocity meter was used to record signals from the pulmonary artery in 52 normal subjects ranging in age from less than 1 week to over 30 years. Signals were obtained from an unfocused transducer in the second or third left intercostal space using a 2.25 MHz instrument. The increase in mean velocity at the start of systole followed a linear pattern for at least the first 45 ms of ejection, irrespective of the age or size of the subject. The value for the acceleration at the start of systole decreased during childhood, reaching less than half that in the aorta in adults, and the duration of the linear increase in velocity increased. The pulmonary arterial signals in newborn infants closely resembled those in the aorta. The range of frequencies seen in the sample volume in the adult pulmonary arterial signals was greater than that in the aorta, whereas in infants it was indistinguishable from that in the aorta.

A transmission line model of the normal aorta and its branches.

A computer model of the aorta and its branches was made based on a simulation of an electrical transmission line using T elements. The model represented the aorta, with branches to the arms and legs and a branch to the head. The values for the capacitance and inductance of each T element could be specified, and a linearly increasing left ventricular pressure was used to drive the model. Transmission line equations were used to select values for the components, and an attempt was made to simulate the results of measurements of blood velocity in the aorta and peripheral arteries of normal subjects. The values obtained with the model showed a close relation to those in experimental studies. The results support the hypothesis that the arterial bed can be well represented by a "lossless" branched transmission line, with impedances matched at each branch and terminated with resistances that give a reflection coefficient of 0.5. A driving function, in which a linearly increasing left ventricular pressure provided a transient input to an aortic root of relatively low impedance, gave the best simulation of the experimental results.

Echographic application of the Gorlin formula for assessment of aortic stenosis: correlation with cardiac catheterization in pediatric patients.

We have investigated the use of M-mode echocardiography for the diagnosis of aortic valve stenosis by application of the Gorlin formula. The hemodynamic parameters which enter this formula are shown to derive wholly from noninvasive measurements. The predicted valve areas correspond with those derived by classical catheterization studies at a level of r = 0.89, SE = 0.11 cm2, n = 10. These results suggest that the Gorlin formula for aortic stenosis may have application in a noninvasive context.

Non-invasive ultrasonic cardiac output measurement in intensive care unit.

A non-invasive method for measuring cardiac output utilizing M-mode echography and pulsed Doppler ultrasound is described. Measurements were obtained in 26 of 29 randomly selected, mechanically ventilated patients. These values were compared with simultaneously measured cardiac outputs by thermodilution. There was a statistically significant linear relationship between Cardiac Output measured by Doppler (DCO) and Thermodilution (TDCO): DCO = 0.86 TDCO + 0.29 l/min (r = 0.96, n = 26, SEE = 0.45 l/min) over the range of 1.75-8.5 l/min. DCO had the additional advantage of measuring peak flow velocity and maximal blood flow acceleration during early systole, indices of left ventricular pumping ability. Ultrasonic monitoring of cardiac output may be an important supplement to invasive methods in critical care.

Doppler ultrasonic investigation of Raynaud's phenomenon: effect of temperature on blood velocity.

We have used spectral analysis of signals from a pulsed, range-gated Doppler ultrasonic instrument to make quantitative measurements of arterial blood flow velocity in the hands of normal subjects and persons with Raynaud's phenomenon. We measured the peak velocity during the cardiac cycle and the time integral of the velocity signal over the cardiac cycle. This latter parameter gives a sensitive indication of the degree of vasoconstriction in response to cold. Our preliminary results, based on findings in 13 subjects, suggest that Doppler ultrasound can differentiate persons with Raynaud's phenomenon from normal subjects.

Spatial and temporal resolution of aortic Doppler blood velocity signals in normal human subjects.

We have used digital, microcomputer-based methods for the numerical analysis of pulsed, range-gated, ultrasonic Doppler blood velocity signals recorded with an axially aimed transducer from the ascending aorta of normal subjects. We investigated the spatial, temporal and amplitude resolution of our methods for recording and analysis, comparing aortic signals with test signals from a sine wave function generator. The spatial resolution of our system was found to be adequate in spite of the use of a relatively large sample volume. The temporal resolution was significantly influenced by the rate of change of velocity which affected the results of discrete fast Fourier transform analysis. The rate of increase in aortic blood velocity at the start of ejection was linear, following an initial jump in velocity. The amplitude resolution was affected by fluctuations in the amplitude of the Doppler signals. We conclude that our methods do not exaggerate the bluntness of the aortic velocity profile or the linearity of the increase in blood velocity at the start of left ventricular ejection.

Quantitative ascending aortic Doppler blood velocity in normal human subjects.

We have developed digital, Apple II microcomputer-based methods for the numerical analysis of pulsed, range-gated, ultrasonic Doppler blood velocity signals. These methods were then used to analyse Doppler data recorded every 5 ms from the ascending aorta via the suprasternal notch in normal subjects ranging in age from 3 to 62 years. Normal values for peak velocity, the integral of velocity over the time of systole, and the rate of change of velocity in early ejection are reported. It was found that, after an initial step increase, the velocity of blood flow in early ejection increased in a linear manner in more than two thirds of the individual beats analysed. The time for which the linear acceleration in the aorta was constant (circa 50 ms) was unrelated to the age or size of the subject.

Simultaneous Doppler blood velocity measurements from aorta and radial artery in normal human subjects.

We used two independent, pulsed, range-gated, ultrasonic, Doppler blood velocity meters to record blood velocities in the aorta and a peripheral artery in 32 normal subjects aged 8 to 62 years. Aortic signals were obtained from an unfocussed transducer in the suprasternal notch using a 2.25 MHz instrument. Simultaneous tracings were obtained from the radial or posterior tibial artery using an 8 MHz instrument. The audio Doppler signals were subjected to spectral analysis and mean velocity was calculated at 5 ms intervals during 11 successive heart beats at each site. The increase in mean velocity at the start of systole in the aorta followed a linear pattern for the first 45 ms of ejection in two thirds of the beats, irrespective of the age or size of the subject. A similar linear velocity increase in early systole was seen in the peripheral arterial signals after a delay due to the time taken for the flow wave to pass to the periphery. Thus the constant acceleration seen in aortic blood velocity tracings is transmitted to peripheral arteries in an attenuated and delayed but undistorted form.

Skin gas tensions and resistances measured by mass spectrometry in adults.

We used a dual-sampling chamber 2.5 cm in diameter, controlled by an Apple II microcomputer, to measure gas tensions in the skin of adults by mass spectrometry. The tensions of O2, CO2, N2, and water vapor and the resistances to the flows of gases through the skin were calculated from the voltages for the different gases passing through two separate membranes of different permeability. We compared the skin O2 and CO2 tensions with arterial values in 13 patients with lung disease during a standardized exercise test. The skin values followed changes in the arterial values. The regression line relating skin to arterial O2 tension had a slope of 1.05 and that for CO2 a slope of 1.51. We conclude that mass spectrometry is capable of providing measurements of gas tension from the heated skin that are similar to those found using electrochemical methods in adults.

An intercostal retractometer for estimation of intrapleural pressure changes in infants.

An intercostal retractometer was developed for estimation of intrapleural pressure changes in infants. It consists of a flat reference plate which floats over the interspace and is attached to the skin by a flexible plastic film. The pressure inside the device is measured with a strain gauge. The volume inside the device is adjusted, so that the intercostal space is brought to a condition of flatness and pressure changes in the device correlate linearly with intrapleural pressure changes. The retractometer is calibrated against overall intrapleural pressure changes by matching its output to changes in airway pressure during occlusion of the airway. The calibration factor is qualitatively proportional to the thickness of the subcutaneous tissue. Retractometer and intrapleural pressures were simultaneously measured in two infant rhesus monkeys with small pneumothoraces. Esophageal and retractometer pressures were compared in seven preterm infants with an average weight of 1345 g. The device estimated the monkeys' intrapleural pressure changes to within 1.2 cmH2O and the human preterm infants' esophageal pressure changes to within 1.3 cmH2O (95% confidence limits of a linear regression).

Comparison of methods of recording and analysis of Doppler blood velocity signals in normal subjects.

Doppler blood velocity signals were recorded from the aorta and pulmonary artery in normal adults, children and premature infants, using three different pulsed, range-gated instruments. The tracings analyzed by three independent methods of spectral analysis with axially aimed transducers showed velocity patterns with a narrow range of frequencies (blunt velocity profile) with a constant acceleration of blood flow in early systole. A similar velocity pattern was seen in the premature infant's aorta in which the transducer beam was larger than the vessel insonated. We conclude that the normal velocity pattern in the central circulation is close to blunt, and that tracings obtained with transducers that insonate varying proportions of the vessel give similar signals.

Transfer of oxygen, nitrogen, and carbon dioxide through normal adult human skin.

The resistance to the flow of oxygen, nitrogen, and carbon dioxide through the skin ws measured in three normal adult human subjects. A sampling chamber 2.5 cm in diameter, heated to 43-44 degrees C, was applied to the skin of the forearm and gas sampled with a mass spectrometer at a rate of about 10(-5) ml . s-1 through membranes of different resistance. Skin resistance was calculated from the results of sequential studies with different membranes of known resistance on the sampling chamber. The resistance to oxygen flow (1.79 +/- 0.92 X 10(3) atm . ml-1 . min . cm2) was 1/5 of that for nitrogen and 28.5 times that for carbon dioxide. The response time of the skin to a sudden change in arterial gas tension was investigated by having the subjects rebreathe 5% carbon dioxide in oxygen and then breathe air. The mean transit times though the skin for oxygen and carbon dioxide were similar (approx 30 s) and about twice those for nitrogen. The finding of similar response times for oxygen and carbon dioxide transfer in the face of large differences in resistance suggests that there is a high capacitance for carbon dioxide in the skin, presumably due to its high solubility and the effects of buffering.

Partial deficiency of carnitine palmityltransferase: physiologic and biochemical consequences.

Deficiency of muscle carnitine palmityltransferase (CPT), first described in 1973 by DiMauro and associates, is proving to be one of the principal causes of recurrent paroxysmal myoglobinuria. In this disease, oxidation of lipid substrates is impaired, because CPT is necessary for the transport of long-chain fatty acids through the inner mitochondrial membrane. As a result, patients depend excessively on carbohydrate metabolism as a source of energy for muscular work.