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The calibration of gas volume measuring devices at continuous and pulsatile flows.

A gas circuit that was capable of passing continuous or pulsatile flows via a 350 L Collins chain-compensated gasometer was built and evaluated. Various turbine volume transducers and dry gas meters were tested with gas compositions and flows that mimicked: a) inspired pulsatile flow over the physiological range and, b) mixed expirate being withdrawn from a Douglas bag. We found the Collins gasometer to be very accurate throughout its elevation, but its mixing fan is not required and atmospheric air should be left to saturate and the added water vapour calculated. Dry gas meters can be accurate to within 1% when calibrated (60 to 150 L/min), but require at least 25 L to be passed through them. The Morgan Ventilometer is an extremely reproducible device (coefficient of variation 0-0.2%, n = 60), but an increase in calibration syringe rate will elevate the calibration factor and reduce the percentage accuracy (one unit increase in calibration factor reduces accuracy by 0.6 - 1.0%). The optimal calibration syringe rate appears to be 30 - 45 b/min. Entrainment through the attached respiratory tubing can also alter the validity of the Ventilometer's calibration procedure.

Equipment Design

Comparison of steady and pulsatile flow near the ventral and dorsal walls of casts of human aortic bifurcations.

Steady and pulsatile flows were passed through casts of human aortic bifurcations and, by means of a laser Doppler anemometer, fluid velocities were measured at selected sites near the ventral and dorsal walls. At these sites, in the vicinity of the bifurcation, the influence of secondary flow is significant and therefore an appreciation of the phasic variation of secondary flow patterns is important. Results are presented comparing the flow direction in both steady and pulsatile flow at sites in three casts. The common features of the flow at these sites were the persistence of the flow direction during the accelerating and decelerating phases of the pulsatile cycle, and the consistently smaller angle (measured from the inlet centerline) of the pulsatile flow direction as compared to the angle of the flow direction in steady flow.

Aorta

A continuous and pulsatile flow circulation system for evaluation of cardiovascular devices.

The design of a nonpulsatile and pulsatile system using a centrifugal pump is presented. To induce a pulsatile flow with a centrifugal pump, an independent pneumatically driven unit provided flow patterns over a wide range of frequencies and amplitudes. The pulsatile flow was generated by the axial displacement of a cylinder that periodically compressed the flexible conduit that is connected to the pump. The system can accommodate flow rates up to 6,000 ml/min and transmural pressures up to 500 mm Hg and is capable of maintaining the pressure at a constant value. This circuit produced reproducible pressure waves having a frequency up to 4 Hz. The periodicity of the transmural pressure between 80 and 180 mm Hg was similar to the pressure wave propagation observed in peripheral circulation. Capable of adequately reproducing continuous and pulsatile flow, the apparatus is therefore versatile to allow in vitro evaluation of cardiovascular devices.

Centrifugation

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions.

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.

Adenocarcinoma

Steady and pulsatile flow distribution in a multiple branching network with physiological applications.

Flow rate of distribution in steady and pulsatile flow is investigated in a multiple branching network including six successive generations in the same plane. In this model, the geometry dependence of flow rate distribution has already been pointed out in steady flow (previous study) by observing the occurrence of non-uniform flow rate distribution at terminal orifices despite the symmetrical dichotomy, identical distance and cross-sectional profile of the 64 parallel pathways. In the present study, we point out two additional properties of the steady flow rate distribution. (i) The flow rate distribution is not markedly sensitive to a change in viscosity and therefore Reynolds number does not appear to be a determinant factor to modify the flow distribution. (ii) The effect of a branch obstruction on flow rate distribution is limited in space and its extension remains the same for the different Reynolds numbers tested. These properties also characterize the interdependence between the model geometry and the flow distribution in steady state. The results obtained in pulsatile flow show that the flow distribution remains similar to steady state as long as the parameter lambda = Qp/Qs (Qp = amplitude of flow oscillation, Qs = steady component of the total flow) is less than 1. When lambda is greater than 1, the flow distribution may become uniform, which means that contrary to the steady flow case, the velocity profiles become rapidly symmetrical downstream from the bifurcations. Physical explanations for this are proposed after considering the theoretical problem of pulsatile developed flow in a straight tube. In this case, the parameter lambda again plays a crucial role in the velocity distribution.

Arteries

Effects of pulsatile flow on cultured vascular endothelial cell morphology.

Endothelial cells (EC) appear to adapt their morphology and function to the in vivo hemodynamic environment in which they reside. In vitro experiments indicate that similar alterations occur for cultured EC exposed to a laminar steady-state flow-induced shear stress. However, in vivo EC are exposed to a pulsatile flow environment; thus, in this investigation, the influence of pulsatile flow on cell shape and orientation and on actin microfilament localization in confluent bovine aortic endothelial cell (BAEC) monolayers was studied using a 1-Hz nonreversing sinusoidal shear stress of 40 +/- 20 dynes/cm2 (type I), 1-Hz reversing sinusoidal shear stresses of 20 +/- 40 and 10 +/- 15 dynes/cm2 (type II), and 1-Hz oscillatory shear stresses of 0 +/- 20 and 0 +/- 40 dynes/cm2 (type III). The results show that in a type I nonreversing flow, cell shape changed less rapidly, but cells took on a more elongated shape than their steady flow controls long-term. For low-amplitude type II reversing flow, BAECs changed less rapidly in shape and were always less elongated than their steady controls; however, for high amplitude reversal, BAECs did not stay attached for more than 24 hours. For type III oscillatory flows, BAEC cell shape remained polygonal as in static culture and did not exhibit actin stress fibers, such as occurred in all other flows. These results demonstrate that EC can discriminate between different types of pulsatile flow environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Design of a physiologic pulsatile flow cardiopulmonary bypass system for neonates and infants.

Cardiopulmonary bypass surgical techniques that allow a surgeon to operate on the infant's heart use an extracorporeal circuit consisting of a pump, oxygenator, arterial and venous reservoirs, cannulae, an arterial filter, and tubing. The extracorporeal technique currently used in infants and neonates is sometimes associated with neurologic damage. We are developing a modified cardiopulmonary bypass system for neonates that has been tested in vitro and in one animal in vivo. Unlike other extracorporeal circuits which use steady flow, this system utilizes pulsatile flow, a low prime volume (500 ml) and a closed circuit. During in vitro experiments, the pseudo patient's mean arterial pressure was kept constant at 40 mmHg and the extracorporeal circuit pressure did not exceed a mean pressure of 200 mmHg. In our single in vivo experiment, the primary objective was to determine whether physiologic pulsatility with a 10 F (3.3 mm) aortic cannula could be achieved. The results suggest that this is possible.

Animals

[Clinical effect of high-flow pulsatile cardiopulmonary bypass in coronary artery bypass grafting].

The effect of high-flow pulsatile cardiopulmonary bypass was evaluated in 36 patients undergoing coronary artery bypass grafting in our unit. The patients were divided into two groups, based on cardiopulmonary bypass (CPB) flow; high (3.0 +/- 0.2 l/min/m2), or moderate (2.4 +/- 0.2 l/min/m2). Multidose cold crystalloid cardioplegia was administered for myocardial protection. Pulsatile flow during CPB was used and systemic perfusion pressure was maintained between 50 and 80 mmHg. Preoperatively, there were no differences between groups in left ventricular ejection fraction or extent of coronary artery disease. The times required for CPB and weaning from CPB were significantly shorter in high-flow group than moderate-flow group. The urinary output during CPB was significantly higher in high-flow group than moderate-flow group. Postoperatively, there were no significant differences in the incidence of myocardial infarction, stroke, or 30-day mortality between groups. In conclusion, high-flow pulsatile CPB shortens the length of CPB and does not differ significantly from moderate-flow with respect to mortality and morbidity.

Aged

Cyclic variation of Doppler power from whole blood under pulsatile flow.

The echogenicity and Doppler power from whole blood under pulsatile flow have been found to vary during the flow cycle in previous studies both in vitro and in vivo. The present study was undertaken to better understand this phenomenon. Doppler power from whole blood under pulsatile flow was measured with a pulsed Doppler flowmeter as a function of the flow cycle, radial position and compliance of the vessel in a mock flow loop. It was found that the cyclic variation is more pronounced if the stroke rate is less than 56 beats/min and that the peak of the Doppler power from whole blood flowing near the center stream coincided with the peak of the flow velocity. However, it began to lead the velocity peak as the measurement site was moved away from the center stream. The lead increased as the radial distance was increased. The results also show that the compliance of the vessel can affect, to a certain extent, the magnitude of the cyclic variation. Results from intravascular Doppler measurements rule out the possibility that the cyclic variation is primarily due to the variation in attenuation caused by vessel wall during a flow cycle.

Animals

Effects of velocity profile of to-and-fro pulsatile flow on magnetic resonance signal intensity.

The effects of to-and-fro pulsatile flow, i.e., an oscillatory fluid motion with no net flow, on signal intensity in gated spin-echo magnetic resonance imaging are considered both theoretically and experimentally. On the basis of hydrodynamic principles, to-and-fro pulsatile flow at large Womersley numbers consists of uniform inner flow and boundary-layer-type flow adjacent to a tube wall. Therefore, the velocity profile is "trapezoidal" rather than parabolic at all times during the pulsation period. Contrary to the absence of phase dispersion and loss of signal within the inner flow where no velocity gradient exists, large velocity differences cause phase dispersion and, hence, loss of signal within the boundary layer, whose thickness is inversely proportional to the Womersley number. An understanding of these features of to-and-fro pulsatile flow provides the theoretical basis of cerebrospinal fluid flow phenomena in magnetic resonance imaging, since this type of flow exists in cerebrospinal fluid pathways.

Cerebrospinal Fluid

A comparison of steady and pulsatile flow in symmetrically branched tubes.

The purpose of this study was to compare the characteristics of flow in the region of symmetrical bifurcations having branch-to-trunk area ratios of 0.4, 0.8 and 1.2 during steady and pulsatile flow. Flow was visualized with neutrally bouyant particles. Secondary flow was not observed in the branches during either steady or pulsatile flow when the branch-to-trunk area ratio was 0.4. Secondary velocity patterns were not observed in the branches with branch-to-trunk area ratios of 0.8 and 1.2 during pulsatile flow, although they were observed during steady flow. It may be inaccurate, therefore, to characterize pulsatile flow at an instantaneous Reynolds number on the basis of steady flow at the same Reynolds number.

Aorta

Effect of pulsatile flow during cardiopulmonary bypass on thyroid hormone metabolism.

Changes in thyroid hormone levels during and after cardiopulmonary bypass (CPB) are well documented. However, little is known about the effects of pulsatile flow during CPB on thyroid hormone metabolism. To examine the effect of flow pattern, a prospective study was carried out using 30 patients undergoing coronary artery bypass grafting. Fifteen patients had pulsatile flow during CPB and 15, nonpulsatile flow. Serum samples were obtained preoperatively, during bypass, and at 2 and 24 hours postoperatively. Thyroid-stimulating hormone, thyroxine (T4), triiodothyronine (T3), free T4, and free T3 levels were measured by radioimmunoassay. All measured hormone levels except free T4 and thyroid-stimulating hormone decreased after the initiation of CPB. There were no differences in preoperative values between the two groups. However, levels of T3 and free T3 during and after CPB showed a significant difference between the two groups, with a smaller decrease in patients in whom pulsatile flow was used during bypass (p < 0.05). Thyroxine, and thyroid-stimulating hormone free T4 values showed no difference between the two groups at any sampling time. These data provide support for the use of pulsatile flow during CPB to establish a more physiologic state and maintain better thyroid hormone metabolism.

Cardiopulmonary Bypass

Cardiac-gated MR angiography of pulsatile flow: k-space strategies.

Signal strength in time-of-flight magnetic resonance (MR) angiography of pulsatile flow is modulated by the time-varying intraluminal magnetization strength. The specific appearance of MR angiographic images therefore depends on the relationship of different phase-encoding steps to the pulsatile flow waveform. Cardiac-phase gating can be applied with phase-encoding reordering to acquire different regions of k-space during the desired phases of the cardiac cycle. The authors have developed a simulation program for evaluating the merits of different encoding strategies for pulsatile flow. The model was validated with phantom studies. High signal intensity relative to that in conventional MR angiographic studies can be attained with strategies that impose relatively small penalties in total acquisition time.

Artifacts

A cardiac phantom and pulsatile flow pump for magnetic resonance imaging studies.

Fast scan magnetic resonance imaging (MRI) acquisitions are a rapid noninvasive means of evaluating the cardiovascular system. Because the appearance of flowing blood is highly variable, the interpretation of these images is sometimes difficult. A nonferromagnetic phantom that could generate lifelike pulsatile flow and also simulate the motions of the beating heart would facilitate image interpretation. This paper describes an MRI-compatible cardiovascular phantom that mimics the motions of the heart and also creates physiologic pulsatile flow. The phantom consists of a ventricle and an air pump that drives it. The pump is connected to the ventricle with seven meters of air hose so that the pump (which has ferromagnetic parts) can be placed outside the magnet room. The ventricle is placed in an airtight Plexiglas cylinder and the pump alternately pressurizes and depressurizes the cylinder, driving fluid in and out of the ventricle. The motions of the ventricular wall simulate the motions of the heart, and the pulsatile flow generated is of physiologic velocities and volumes. This phantom also can be used with other methods of evaluating cardiovascular function, such as MUGAS, angiography, and Doppler, allowing correlation between MRI and other modalities. Finally, the phantom can be used to study almost any aspect of cardiovascular function from pulsatile flow velocity to ventricular studies (ejection fractions, cardiac output, wall motion) and even studies of stenotic or regurgitant valves.

Heart

Quantification of pulsatile flow during cardiopulmonary bypass to permit direct comparison of the effectiveness of various types of "pulsatile" and "nonpulsatile" flow.

The relative merits of adding a "pulsatile" component to flow during cardiopulmonary bypass (CPB) has long generated controversy, the resolution of which has been hampered by lack of quantification of the "pulsatility" delivered by different devices. The present experimental series had two goals: to quantify the "pulsatility" of blood flow during CPB in terms of pulse rate and pulsatility index (PI) and to examine which aspects of a "pulsed flow" provide clinical benefits. A flow waveform can be expressed in terms of its baseline rate and its PI, the sum of the square of its harmonics components divided by the square of the mean flow. We used PI to quantify the pulsatility of blood flow in the descending thoracic aorta and used changes in the serum lactate level as an indication of end organ flow. In one experimental series seven adult mongrel dogs were placed on roller pump CPB at a constant flow of 100 ml/kg/min. After a 20-minute stabilization period a roller pump wave and three different pulse shapes (generated by a computer-controlled hydraulic pump) were evaluated for 15 minutes each. The pulse wave shapes were graded, with C being the sharpest and A the least sharp. In a second series six other dogs were placed on CPB and were subjected to roller pump perfusion and three pulse waves of identical shape but at different rates. The results indicated that a combination of a minimum PI of 1.88 and a minimum rate of 80 bpm were necessary to significantly reduce lactate production as compared with roller pump perfusion. Thus the same mean flow can have very different physiologic effects depending on how it is delivered. This quantification method permits direct comparison of different "pulsatile waveforms" and provides a means for identification of optimal pulsatile flow.

Animals

Bi-directional cavopulmonary shunt: is accessory pulsatile flow, good or bad?

OBJECTIVE: Evaluation of the effect and long-term outcome of accessory pulsatile blood flow versus classical bi-directional cavopulmonary connection (BCPC). METHODS: Retrospective review of the medical and surgical records. RESULTS: Two-hundred and five patients (119 boys, 86 girls) underwent BCPC from 1990 to 1996. Accessory pulsatile flow was present in 68%, flow being maintained through the pulmonary trunc in 46%, systemic-to-pulmonary artery shunt in 13% and mixed in 7%, or patent ductus arteriosus in 2%. Patients with accessory pulsatile flow had lower hospital mortality (3% versus 5%), while mean pulmonary artery pressure (14.1 versus 12.6 mmHg P = 0.050) and increase of oxygen saturation (12.4 versus 8.7, P = 0.034) were significantly higher. The period of artificial ventilation (1.9 day) and ICU stay (6 days) did not differ for both groups. Late mortality was higher following accessory pulsatile flow (6% versus 1%). At late follow-up patients with accessory pulsatile flow had significantly higher oxygen saturation (mean 85 +/- 4%, versus 79 +/- 4%; P < or = 0.005). If subsequent completion of Fontan is considered the optimal palliation and subsequent systemic to pulmonary artery shunt, arteriovenous fistula and transplantation is considered a failure, patients with accessory pulsatile flow had significantly more and earlier completion of the Fontan procedure (mean 1.7 +/- 2.4 years, versus 2.7 +/- 4.4 years; P = 0.008). Survival is not influenced by age at bi-directional cavopulmonary shunt surgery, left or right functional ventricular anatomy or previous palliative surgery. One patient with accessory pulsatile flow developed systemic-to-pulmonary collateral's eventually requiring lobectomy. CONCLUSION: Despite two different initial palliative techniques the outcome was not significantly different. Accessory pulsatile blood flow appeared not to be a contra-indication for a completion Fontan procedure. Moreover, the data suggest that after accessory pulsatile flow can safely be performed, at late follow-up oxygen saturation is higher, while, significantly more and earlier completion of Fontan occurred. Age at bi-directional cavopulmonary shunt, basic left or right ventricular anatomy or previous palliative surgery did not influence survival.

Adolescent

Magnetic resonance assessment of the pulmonary arterial trunk anatomy, flow, pulsatility and distensibility.

We used magnetic resonance imaging with cine velocity mapping to study the anatomy of pulmonary bifurcation and to measure volume blood flow, pulsatility of flow and arterial wall distensibility in the central pulmonary arteries of nine healthy volunteers. Multislice, multiplane spin echo images were acquired to display pulmonary bifurcation anatomy. Diameters of the main pulmonary artery (MPA) in systole were 2.56 +/- 0.35 cm and in diastole 2.20 +/- 0.33 cm. Those of the right pulmonary artery (RPA) were 1.57 +/- 0.29 cm and 1.39 +/- 0.23 respectively, and of the left pulmonary artery (LPA) 1.79 +/- 0.26 cm and 1.55 +/- 0.10 cm respectively. A gradient echo sequence with phase shift velocity mapping was then used to measure flow in MPA, RPA and LPA 2 cm on either side of the pulmonary bifurcation. Time averaged flow, calculated from mean velocity and the cross-sectional area of the vessels was 4.99 +/- 1.10 l.min-1 in MPA, 2.23 +/- 0.58 l.min-1 in RPA and 2.31 +/- 0.63 l.min-1 in LPA. The pulsatility index of flow derived from peak forward flow, peak backward flow and time averaged flow were as follows: MPA 4.4 +/- 0.8, RPA 5.1 +/- 0.6 and LPA 4.6 +/- 1.5. Distensibility, calculated from the change in cross-sectional area between diastole and systole and expressed as percentage were as follows: MPA 25.6 +/- 10.7, RPA 21.4 +/- 10.7 and LPA 24.5 +/- 7.8. MRI with velocity mapping accurately characterized anatomy, flow, distensibility and pulsatility of the central pulmonary arteries.

Adult

Preload-responsive, pulsatile-flow, externally valved pump: cardiopulmonary bypass.

Currently two pumps are used for cardiopulmonary bypass, the roller pump and the centrifugal or vortex pump. Both are steady-flow pumps. The procedure of cardiopulmonary bypass possesses a finite morbidity and mortality. The degree to which steady flow is responsible for this morbidity and mortality remains to be clarified, but investigators have established the fact that a physiologic degree of pulsatile flow must be achieved before its beneficial results, such as normal systemic resistance and absence of lactate production, can be demonstrated. Availability of a satisfactory pulsatile pump for cardiopulmonary bypass has been a problem in the past but the pump presented here may satisfy this need. It produces physiologic pulsatility with rate dependent ejection time equal to or less than that of humans (413 microseconds minus 1.7 times heart rate), and it is preload-responsive, varying its pumping rate and output with filling pressure. The pump is externally valved to minimize hemolysis, which has been demonstrated in two laboratory studies to be significantly less than with the roller pump. It produces pulsatile flow through membrane oxygenators. The pump is thought to have potential for several clinical applications in addition to (1) pulsatile-flow cardiopulmonary bypass, including (2) left, right, or combined transthoracic QRS synchronized ventricular assist, (3) femoral vein to femoral artery QRS synchronized left ventricular assist, (4) adult or infant ECMO, (5) pulsatile flow hemodialysis. In the latter, spallation and embolization of hemodialysis tubing particles should not be a problem as has proved to be the case with the present hemodialysis pump.

Cardiopulmonary Bypass