Search

The determinants of the shape of the pulmonary input impedance spectrum were investigated using a mathematical model based on Womersley's equations for pulsatile flow in constrained viscoelastic tubes and structural data (morphometry, elasticity, and rheology) provided for the entire cat lung by Zhuang et al. Mean distending pressures and diameters of vessels were determined from the structural data and four independent variables: cardiac output and left atrial, pleural, and alveolar pressures. Studies were performed in a control model and a model whose structure was designed to imitate that of a subject with pulmonary vascular impairment. Model simplifications were investigated. Increasing left atrial pressure or cardiac output caused passive distention of vessels that increased total blood volume and decreased vascular resistance, creating a slight spectral shift downward and to the right. Increasing pleural pressure decreased total blood volume and increased vascular resistance, creating a spectral shift upward and to the right. Increasing levels of alveolar pressure resulted in increased vascular resistance and pressures and a shift in blood volume from the capillaries to the arteries without significant change in total blood volume, creating a spectral shift that was slightly downward and to the right . Model simplification studies demonstrated that (1) all vessels distal to the tenth generation (arteries with zero distending pressure diameters < 50 μM) can be modelled as a simple resistor or (2) all vessels distal to the fourth generation can be modelled as a modified Windkessel. Results obtained from the passive studies were consistent with those obtained from normal lambs and lambs with chronically elevated pulmonary blood flow. To model a hypertensive state created by injury to the lung microvasculature, the number and size of small vessels and the compliance constants of all arteries were decreased and the viscoelastic constant was increased, which created the requisite shift to the right and upward. To better match the modulus fluctuation and negative phase angles at higher frequencies in the hypertensive animals, the development of a major reflection site between the main and branch arteries was hypothesized.

We studied the detailed profiles of blood flow in the right and left pulmonary arteries using 20 MHz pulsed Doppler ultrasound equipment in a lamb model. Fourteen lambs aged four to six weeks were selected. In six lambs, monocrotaline pyrrole was injected parenterally to create pulmonary hypertension (PH group). Eight other lambs served as unaltered controls (control group). The blood flow velocities were sampled in 1mm increments along the anterior-posterior axis of the branch arteries. The maximum velocity of the forward flow in the left pulmonary artery was higher than that in the right pulmonary artery in the control group (71.7 +/- 15.9 cm/s vs 60.2 +/- 13.5; p < 0.05). The fastest backward flow was located at the posterior position of the vessel in the right pulmonary artery in the control group (71.7 +/- 15.9 cm/s vs 60.2 +/- 13.5; p < 0.05). The fastest backward flow was located at the posterior position of the vessel in the right pulmonary artery in the control group. No significant bias in location was shown in the left pulmonary artery. Using indices of P90, acceleration time, P90*AcT, the velocity waveforms in the PH group were compared with those in the control group. In the left pulmonary artery, every index in the control group showed a significantly greater value that in the PH group. On the other hand, no significant differences were found between either group in the right pulmonary artery.

For a better understanding of the characteristics of blood flow in the pulmonary artery, we constructed three-dimensional images of velocity profiles of blood flow in the pulmonary artery from pulsed Doppler ultrasound recordings in 14 lambs aged 28-40 days. In 8 lambs, pulmonary hypertension was created by the central venous injection of monocrotaline pyrrole. Six lambs served as unaltered controls. The velocity data were sampled in 2 mm increments along both an anterior-posterior axis and a right-left orthogonal axis in the main pulmonary artery. Using a computer-generated cross-sectional velocity matrix consisting of 0.25 mm square grids, the velocity of blood flow was estimated at each intersection. The cross-sectional velocity matrices were generated at 5 msec intervals during the entire cardiac cycle. In all animals, significant velocity reversal was detected near the posterior wall. In 7 of 14 animals, the peak forward velocity was located near the posterior wall. Three of 8 hypertensive models showed reacceleration during the mid-systolic phase at the center of the velocity waveform, but one reacceleration disappeared at a point only 2 mm away from the center of the vessel toward the posterior wall. Acceleration time correlated well with the mean pulmonary arterial pressure (PAP) (r = -0.85) and the log10 PAP (r = -0.86). Corrected acceleration time (acceleration time divided by the square root of the cardiac cycle length) also correlated with PAP (r = -0.78) and the log10 PAP (r = -0.81).

METHODS The nature of the velocity profiles in the main pulmonary artery was examined in two dimensions using growing lambs. Lambs in two age groups--2 weeks and 4 weeks were selected for study. Using an intraluminal 20 MHz pulsed Doppler probe, pulmonary blood velocity waveforms were recorded at 2 mm intervals along two axes: the anteriorposterior axis (AP) and the right-left axis (RL). Instantaneous velocity profiles were computed throughout the cardiac cycle and the characteristics of the profiles examined. Results obtained along the anterior-posterior axis were consistent with findings previously obtained; marked negative velocity along the posterior wall was observed. However, unlike the findings in previous studies, negative velocities of lesser magnitude were evident near the left wall of the right-left axis.

A six-element lumped parameter model of the pulmonary circulation was used to evaluate two signal-averaging techniques for calculating the pulmonary input impedance spectra of normal lambs. Pulmonary artery pressure and pulmonary artery flow data obtained simultaneously in the main pulmonary artery were subjected to time-domain averaging and frequency-domain averaging techniques. Input impedance was determined by a cross-power spectral method designed to retain the periodicity of the signals. Preliminary studies indicate that the impedance spectra determined from noise-free input flow data to the model closely approximated the model-derived impedance spectra for a wide range of heart rates. The addition of noise signals to the noise-free input data produced impedance spectra that were consistently in agreement with model spectra for the lower-order (1-3) harmonics but not for the higher-order terms. >

The effects of dopamine on pulmonary and systematic vascular beds were investigated in 8 anesthetized goats (mean age 5+or-1 weeks). Pulmonary artery, aortic, left atrial, and central venous pressures and pulmonary and aortic flows were recorded simultaneously during a 10-minute baseline period and while infusion dopamine at 5, 10, 20, 40 160, and 320 mu g/kg/min. Pulmonary vascular resistance increased significantly at the 20 and 40 mu /kg/min infusion rates, while systemic vascular resistance decreased significantly at these rates. Characteristic impedances indicate generally increased trends. The pulmonary global reflection index indicates increased impedance mismatch at the high infusion rates, while the opposite is true for the systemic reflection index. Right heart work and the energy costs of transporting 1 cm/sup 3/ blood exceed systemic work and energy costs at the high rates of increase the resting tone of the pulmonary vascular bed, while the effect on systemic vascular tone remains unclear. The finding that the work and energy requirements of the heart are substantially increased at the higher infusion rates could affect the therapeutic value of dopamine use at these rates. >

Pulmonary input impedance spectra were estimated in one-month-old lambs whose circulation had been altered during the first few days of life to mimic the pulmonary. hemodynamic states observed in infants and children with left-to-right shunts (high flow) and /or pulmonary vascular obstructive disease (high pressure). Spectral results obtained from the animal models were compared with those obtained from a computer simulation based on morphometric and hemorheologic data compiled for the 4 kg cat. Spectral features examined included the frequency of the first modulus minimum (indicative of the pulse wave reflection and/or pulse wave velocity) and characteristic impedance (average resistance to pulsatile flow). High flow (shunt-open/shunt-closed ratio>2.1) resulted in a slight spectral shift to the right with little change in characteristic impedance in both the lamb and the passive computer simulation models. High pressure (mean pulmonary artery pressure >28 mmHg) in the lamb model resulted in a marked shift to the right with a doubling of characteristic impedance. >

The effects of pulsatile hemodynamics on right ventricle-pulmonary circulation interactions were studied in control lambs and in two lamb models of altered pulmonary hemodynamics induced at infancy: elevated pulmonary arterial pressure (PAP) was created by the infusion of monocrotaline pyrrole (MCTP), and elevated pulmonary arterial blood flow was obtained by the creation of an arteriovenous fistula (Shunt). High-fidelity PAP, midvessel Doppler blood velocity (PAV), and cardiac output (CO) were measured in open-chest, anesthetized lambs. PAV waveforms were normalized to match the measured CO. Measured pressure and flow signals were separated in the time domain into forward and backward components. Pulmonary input impedance and indexes quantifying the timing of the reflected wave pulse (beginning of reflected pulse, duration of reflected pulse in systole, and duration of reflected wave in diastole) were calculated for each group. Results indicate that in control animals the reflected wave returned late in systole and extended through much of diastole, thereby increasing diastolic pressure like a counterpulsation balloon. No significant differences in the timing indexes were found between Shunt and control animals. In the MCTP group, the reflected wave returned significantly earlier than normal with the peak reflected pulse occurring before valve closure. The resulting augmentation of systolic pressure and, therefore, large pulse pressure is consistent with pressure waveforms observed in clinical pulmonary hypertension. We conclude that early wave reflection exerts a detrimental effect in pulmonary hypertension by unfavorably loading the still-ejecting right ventricle.

In vitro pulsatile flow visualization studies were conducted to assess the effects of varying radii of curvature of the right ventricular outflow tract (RVOT) and main pulmonary artery (MPA) on the flow fields in the main, right, and left pulmonary arteries of a one month lamb pulmonary artery model. Three glass flow-through models were studied; one with no curvature, one with the correct anatomic curvature, and one with an overaccentuated curvature on the RVOT and MPA. All other geometric parameters were held constant. Pulsatile flow visualization studies were conducted at nine flow conditions; heart rates of 70, 100, and 140 bpm, and cardiac outputs of 1.5, 2.5 and 3.5 l/min with corresponding mean pulmonary pressures of 10, 20, and 30 mmHg. Changes were observed in the pulmonary flow fields as the curvature of the outflow tract, heart rate and mean pulmonary pressure were varied. An increase in vessel curvature led to an increase in the overall radial nature of the flow field as well as flow separation regions which formed faster, originated further downstream, and occupied more of the vessel area. At higher heart rates, the maximum size of the separation regions decreased, while flow separation regions appeared earlier in the cardiac cycle and grew more quickly. Heart rate also affected the initiation of flow reversal; flow reversal occurred later in the cardiac cycle at lower heart rates. Both heart rate and mean pulmonary pressure influenced the stability of the pulmonary flow field and the appearance of coherent structures. In addition, an increase in mean pulmonary pressure increased the magnitude of reverse flow. These flow visualization observations have directed more quantitative studies such as pulsed Doppler ultrasound and laser Doppler anemometry velocity measurements.

In April 1989, young-of-the-year snapper (Pagrus auratus) were captured from the wild and injected with tetracycline. The fish were reared on natural food in a large pool with flowing sea water under ambient marine conditions. Two fish were removed every two months for two years, and the growth of their otoliths, relative to the tetracycline mark, was measured. Growth of the otoliths was greatest in spring and summer and least during winter. Opaque marks appeared in the otoliths of fish during both winters of the study. Our results confirm that the opaque marks in otoliths of young snapper can be used to determine the age of the fish in years.

The velocity profile of the main pulmonary artery was determined in nine adult, open-chested, mechanically ventilated mongrel dogs using an intraluminal, needle-mounted, range-gated, pulsed Doppler technique. Mean phasic point velocities were determined at 2 mm intervals across the lumen of the vessel, 2 cm above the pulmonary valve, by recording the Doppler shift of an activated 20 MHz piezoelectric crystal, range-gated 3.5 mm in the direction of the pulmonary valve. Mean Reynolds numbers from the main pulmonary artery ranged from 275 to 1140. Radially normalised intraluminal distance versus mean phasic point velocity plots were constructed which demonstrated a curved profile in all 9 dogs. First order regression analysis demonstrated a poor fit (r: 0.05-0.68). Second order (r:0.61-0.97) and third order (r:0.72-0.99) regression analyses markedly improved the fit, confirming the non-linear nature of the velocity profile. Step-wise third order regression analysis to determine the importance of the entry sequence demonstrated that the most important term for determining the regression coefficient was the X2 term in six dogs. In addition, the velocity profile was noted to be shifted, with the highest velocities recorded between the centre of the vessel and the anterior wall in eight of nine dogs (location of highest velocity: +0.26 radius +/- 0.25 (mean +/- SD).

The velocity profile in the ascending aorta, which has been variously reported as parabolic, skewed or flat, was measured using an intraluminal probe equipped with a miniature piezoelectric crystal activated by a 20 MHz pulsed Doppler with a 1 mm3 sample volume size. Phasic velocities, determined via spectral analyses, were obtained at 2 mm intervals across the aortic lumen of anaesthetised open-chest dogs by sequentially moving the crystal between posterior and anterior walls, maintaining the ultrasound beam parallel to the flow axis. Range-gating allowed data acquisition 3.5 mm proximal to the crystal, thus eliminating probe induced turbulence. Time and spatial distributions of velocities over the cross-section were computed. Expected errors in vessel mean velocity estimates based on point measurements were calculated. Analysis of phasic waveforms showed increased posterior velocities during systole but third order regression analysis of normalised point mean velocities across the lumen showed the best fit was a statistically flat straight line. Centreline referenced analyses indicated the expected difference between point mean velocity and vessel mean velocity was maximal (19.3 +/- 10.1%) 4 mm toward the posterior wall and minimal (4.7 +/- 9.1%) 5 mm toward the anterior wall. Anterior posterior wall referenced analyses indicated the most reliable position for estimating vessel mean velocity from point mean velocity along this axis was 5 mm from the anterior wall.

A new method has been developed that permits constant postoperative monitoring of mean and phasic cardiac output in patients after correction of congenital heart defects. A miniature ultrasound probe is attached to the adventitia of the ascending aorta at the conclusion of the operative procedure. This is connected to the monitoring equipment by means of polyurethane-covered wires that exit the chest wall through a small stab wound. The probe can easily be removed by gentle traction when the patient’s condition is stable. The technique was developed, validated, and refined in extensive animal studies, and this report describes the first series of 20 consecutive human implants, performed between August 1984 and September 1985, in which the absolute cardiac output determination obtained with the ultrasound probe at the time of its application was correlated with cardiac output as measured with a standard electromagnetic flow probe. Fourteen male and six female patients (mean age 5.5 years) were studied. Operations performed included eight atrial septal defect repairs, four procedures for tetralogy of Fallot, three ventricular septal defect repairs, three stenotic valve corrections, and two Senning operations. One operative death occurred, but no complications were related to probe application or removal. The average cardiac output in the 20 patients as measured with the ultrasound probe was 2.2 ± 1.1 L/min (range 0.67 to 5.27 L/min). This is nearly identical to the results noted with the electromagnetic flow probe, where the mean cardiac output was 2.3 ± 1.2 L/min (range 0.7 to 6 L/min). Regression analysis revealed a high linear correlation (r = 0.9) between the two techniques. A monitor can display the cardiac output trend with 1 minute updates, which greatly enhance management of intravenous drug therapy and volume administration. In conclusion, this new extraluminal removable probe allows virtually continuous monitoring of the postoperative cardiac output after correction of congenital heart defects and should become a standard technique in the postoperative care of these patients.

To test the sensitivity and accuracy of pulsed Doppler ultrasonography to detect and quantitate left to right aortopulmonary shunt flow, an arterial allograft aortopulmonary anastomosis was constructed in nine adult mongrel dogs. Cardiac output and allograft flow were measured as the diameter of the allograft was varied. Piezoelectric crystals attached to the carotid artery and proximal descending aorta were energized with 20 MHz pulsed Doppler signals. Negative Doppler shift and negative Doppler shift/positive Doppler shift were calculated for seven dogs. All dogs exhibited negative Doppler shift in the carotid artery at zero allograft flow; five of the seven dogs exhibited a similar pattern in the descending aorta. Increasing negative Doppler shift was measured in all dogs from both sites as the allograft flow increased. Excellent linear correlation existed between allograft flow and negative Doppler shift and negative Doppler shift/positive Doppler shift for each dog from both sampling sites. However, marked interanimal variation in the slopes of the linear regression lines existed, making the composite linear correlation very poor. Detection of small left to right aortopulmonary shunting and single measurements to quantitate accurately left to right aortopulmonary shunting introduce errors due to intersubject variation. However, these results suggest that serial ultrasound measurements made over a short time can accurately predict changes in left to right aortopulmonary shunting.

Relationships between pulmonary artery blood velocity patterns and elevated pulmonary artery pressure and resistance were studied in an animal model of chronic pulmonary hypertension. Monocrotaline pyrrole was injected into the right atria of 1-3-day-old lambs. The animals were subjected to an acute terminal study 4-6 weeks postinjection. Using an intraluminal 20-MHz pulsed Doppler probe, pulmonary blood velocity was measured at 2-mm intervals across the posterior-anterior axis, from which 2-D instantaneous velocity profiles were reconstructed and the characteristics of the waveforms examined. Preliminary computations indicate that the significant increase in pulmonary blood-flow reversal observed near the posterior wall in normal lambs with acute pulmonary hypertension created by hypoxia is not always present in animals with chronic pulmonary hypertension. However, the triangular shape of the waveform associated with pulmonary hypertension is apparent in all studies, and the maximum value of the ratio of reverse flow to forward flow calculated by sampling site correlated significantly with both pulmonary artery pressure and pulmonary vascular resistance. >

Lidocaine is a drug with local anesthetic and antiarrhythmic properties. An inverse relationship is recognized to exist between arterial lidocaine serum levels and cardiac index or liver function [1, 2]. However, the lungs rapidly sequester a significant portion of a lidocaine dose as the drug passes from the right side of the heart into the pulmonary circulation [3]; therefore, a reduction in effective pulmonary blood flow would be expected to raise serum lidocaine concentrations. Hence, patients with congenital heart disease (especially neonates [4]) who have right-to-left intracardiac shunting would potentially be at risk for developing toxic serum lidocaine levels at a lower dose. To test this hypothesis, an animal model of a right-to-left intracardiac shunt was developed to determine the effect of such shunting on lidocaine pharmacokinetics.

The feasibility of measuring pulmonary blood flow (PAQ) continuously using a removable, extraluminal 20 MHz pulsed Doppler probe, which has been used successfully to measure aortic blood flow, was assessed in seven anesthetized mongrel dogs. Simultaneous recordings were made from the Doppler probe (range-gated 5-6 mm from the anterior wall of the main pulmonary artery) and an electromagnetic flow probe (encircling the aorta) over cardiac outputs (CO) ranging from 0.2 to 5.5 L/min. Assuming a flat velocity profile and a fixed cross-sectional area, PAQ was initially calculated as the product of area and mean velocity. Regression analyses (PAQ = a + b X CO) indicated good intraanimal linear correlations in six animals (r greater than or equal to 0.84) and no correlation in one animal (r = 0.003); however, PAQ was consistently higher than CO and interanimal variability was marked, as suggested by large deviations in mean intercept and slope values (a = 1.67 +/- 1.09 L/min and b = 0.70 +/- 0.33). Results improved (r greater than or equal to 0.79 in all animals, a = 0.47 +/- 0.52 L/min, and b = 0.77 +/- 0.21) when the method to estimate PAQ was altered to assume that the starting cross-sectional area was the area that would make baseline PAQ and CO agree, and that the area during each subsequent CO level changed as a function of pulmonary artery pressure and an estimate of pulmonary artery compliance. Results of this study imply that it will be more difficult to use this Doppler probe to monitor CO from the pulmonary artery than it was from the aorta due to the elliptical, more compliant pulmonary vessel walls and the irregular pulmonary artery velocity profile.

Ultrasonic measurement of blood flow within the main pulmonary artery (MPA) requires a precise knowledge of the mean blood velocity within this vessel and the cross-sectional area (CSA). Small conformational changes in the elliptical shape of the MPA have substantial effects on the calculation of CSA and, subsequently, flow. We examined the extent of these changes by measuring the pulsatile and mean elliptical dimensions of the MPA in nine anaesthetised, open-chested, mechanically ventilated mongrel dogs using two pairs of 10 MHz ultrasonic, piezoelectric crystals. These custom-made devices were sutured to the PA adventitia along the long and short cross-sectional axes 2 cm distal to the pulmonary valve. Axial dimensions were collected during normal, elevated (via noradrenaline and fluid additions) and reduced (via exsanguination) PA pressures. We confirmed the linear pressure/diameter response in 15/18 axial data sets (r greater than 0.80). Further, the linear axial responses of the long and short diameters were parallel (7/9, p less than 0.05) and have different zero-pressure intercepts (7/9, p less than 0.0001). A mathematical consequence of this parallelism is predictable, although non-constant, eccentricity. Finally, error analysis of multi-axial measurement techniques were shown to improve CSA accuracy by as much as 50% when compared with uni-axial determinations.

Pulmonary artery blood flow velocity was measured in 15 dogs by a recently developed direct intraluminal pulsed Doppler technique. Changes in velocity characteristics under conditions of experimentally induced hypoxic pulmonary hypertension were observed. Experimental conditions (fractional inspired oxygen concentration = 0.10) produced significant increases in mean pulmonary artery pressure and pulmonary vascular resistance. Overall and maximal negative velocity increased with pulmonary hypertension. Negative velocity occurred predominantly in the posterior half of the pulmonary artery during both control and experimental conditions. With pulmonary hypertension, diastolic negative velocity increased only in the posterior half of the pulmonary artery and systolic negative velocity decreased only in the anterior half. More basic knowledge of pulmonary artery blood flow characteristics may facilitate an informed approach to noninvasive detection of pulmonary hypertension. Direct measurements by this recently developed intraluminal technique will be useful in studying various conditions with altered pulmonary blood flow.