The dynamics of pulsatile blood flow.
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BACKGROUND: The Total Cavopulmonary Connection (TCPC), used for repair of patients with single ventricle physiology, creates a passive system of blood flow into the pulmonary circulation where enhanced energy efficiency may lead to improved long term patient outcomes. Previous numerical and in vitro studies using steady flow have shown that incorporation of SVC (superior vena cava) and IVC (inferior vena cava) offsets lead to decreased energy losses. We hypothesize that the optimal TCPC offset design found in these previous steady flow experiments may not be the optimal design in pulsatile flow situations. MATERIAL/METHODS: 3-D finite volume numerical models were used to simulate flow through the total cavopulmonary connection. We ran steady and pulsatile flow experiments through 4 TCPC designs each with different SVC to IVC offsets (0.1/4, 1/2, 1 diameter offsets). The total energy (power) loss for each TCPC model was calculated. RESULTS: In steady flow experiments, % difference in energy loss between the most optimal and least optimal design was 26%. In contrast, in pulsatile flow experiments the % difference was only 8%. CONCLUSIONS: Our results demonstrate the improvements in energy loss seen using SVC-IVC offsets in steady flow experiments do not necessarily translate to pulsatile flow situations. Overall there was lower differences in efficiency between all TCPC designs in the pulsatile flow experiments. These results emphasize the need for further studies to fully define the relationship between energy losses and TCPC vessel architecture in non-steady flow physiologic situations.
Pulsatile high-flow cardiopulmonary bypass (2.5 l/m2/min with a rectal temperature of 28 degrees C) combined with the Pulsatile Bypass Pump (Kontron Instrument) has been used at Fukuoka Children's Hospital in 259 cases of open-heart surgery in patients less than 1 year of age for a period of 5 years beginning July 1982. The overall results were satisfactory with a surgical mortality of 6.2% (VSD: 96 cases/2 deaths, TGA: 48/1, TAPVD: 34/3, Complete ECD: 15/1, IAA: 10/1, DORV: 10/1, HLHS: 7/4, TOF: 6/0, Truncus Art: 5/0, Others 28/3). The mean duration of cardiopulmonary bypass was 123 +/- 50 minutes during which time the patients had a positive water balance of only 28 +/- 38 ml per kg of body weight. The lowest positive water balance was noted in the patient group with 60-75 mmHg in peak systolic pressure and 30-45 mmHg pulse pressure divided by the pulsatile wave form. This value was significantly lower than other groups of patients with lower or higher peak systolic and pulse pressures. Urinary output during the first 24 hours after operation was 4.1 +/- 1.3 ml/kg/hour. Weight gain on the first postoperative day was 10 +/- 43 g per kg of body weight, and the duration of postoperative respiratory support was 4 +/- 5 days. In conclusion, pulsatile high-flow cardiopulmonary bypass is useful in infant open-heart surgery in light of operative techniques, water balance and postoperative recovery.
An in vitro study was performed to investigate the effects of B(o) inhomogeneity on magnetic resonance images of flow. Controlled inhomogeneity gradients (Gi) were applied and the magnitude of the artifacts produced was quantified for different echo delay times (TE). Both steady and pulsatile flows were examined. In the presence of an inhomogeneity gradient, signal loss is apparent if the flow is pulsatile and/or if the slice thickness is large. The signal loss increases with increasing TE and Gi. With pulsatile flow, ghosting artifacts are also generated. These increase in intensity with increasing TE and Gi. In vivo, field inhomogeneity due to susceptibility variations is large enough to produce these effects. Representative time-of-flight images obtained of a normal volunteer with two different TEs demonstrate the effect in vivo. Flow-related signal loss and artifacts, therefore, increase with increasing TE independent of the moments of the applied gradients.
A novel ungated spiral phase-contrast (USPC) imaging method was developed for rapid measurement of time-averaged blood-flow rates in the presence of pulsatility. The spatial point-spread function was analyzed to provide an intuitive understanding of how spiral trajectories, which sample the k-space origin at every excitation, can mitigate the effects of pulsatility. Pulsatile flow phantom experiments were performed to validate the accuracy and repeatability of the USPC method. The measurement of flow in the renal and femoral arteries of normal volunteers were also performed. The phantom results (error < or = +9%, SD(phantom) < or = 2%, time-averaged pulsatile-flow rates = 3-15 ml/s) and in vivo results (SD(renal) < or = 8%, SD(femoral) < or = 14%) demonstrate the potential of the USPC method for rapidly and repeatedly measuring accurate time-averaged blood flow even in relatively small arteries and in the presence of strong pulsatility.
Several clinical and animal studies have demonstrated that pulsatile perfusion is more beneficial than nonpulsatile perfusion during short or long durations of extracorporeal circulation. Other investigators, however, have been unable to document these benefits. The issue remains controversial. Central to the debate is the issue of a precise definition of pulsatile flow. To help resolve the conflict, pulsatile flow may be quantified in terms of energy equivalent pressure. This formula contains both the arterial pressure and pump flow rate, which are the 2 most critical parameters for open heart surgery. This definition establishes common criteria for assessment of the effectiveness of extracorporeal support.
Empirical correlations for the onset of turbulence in pulsatile flow through a straight tube and a 45 degrees T-bifurcation are presented. We pumped three different test fluids of kinematic viscosity 0.008-0.035 cm2 s-1 through four straight tubes 0.4-3.0 cm in diameter and three 45 degree T-bifurcations 0.45-2.2 cm in diameter. A Scotch yoke mechanism provided an oscillatory sine wave flow component of known stroke volume and frequency. To determine transition to turbulence, we adjusted the mean flow independently until we detected signal instabilities from hot film or electrochemical wall shear stress probes. The critical peak Reynolds number was found to correlate with two independent dimensionless groups: the Womersley parameter and the Strouhal number. We derived power low functions of these groups to provide an accurate and convenient method of predicting transition in both straight and bifurcating tubes. When compared to pulsatile flow through the straight tube, the presence of flow separation within the 45 degrees T-bifurcation induced flow instabilities at lower values of the peak Reynolds number. The correlation for the 45 degrees T-bifurcation is also a suitable model for predicting transition at coronary branch points, which we previously studied in an in vitro pulse duplicator. Flow instabilities at coronary branch points may play an important role in atherogenesis.
1. In six conscious pigs antral, pyloric and duodenal pressures were recorded with a 5.5 cm sleeve sensor and multiple perfused side holes. The manometric assembly was positioned by dual point transmucosal potential difference measurement. Gastric emptying was measured by drainage of the proximal duodenum through a Thomas cannula. Pressures were correlated with emptying of ingested radiolabelled 5% dextrose. Alteration of emptying was produced by infusion into the more distal duodenum of nutrient and non-nutrient solutions of differing osmolalities. 2. Motor activity of the pylorus and antrum was stimulated by ingestion and modulated by intraduodenal infusion. Duodenal infusion of normal saline was associated with antro-pyloric pressure waves and rapid emptying of the ingested liquid. Duodenal infusion of dextrose, fatty acid, amino acids and hyperosmolar saline was associated with stimulation of isolated pyloric pressure waves, suppression of antral pressure waves and slowing of gastric emptying. 3. The dose-response relationship of these effects was investigated using varying rates of intraduodenal dextrose infusions. The emptying rate of the ingested liquid was inversely related to the rates of delivery of dextrose to the duodenum, directly related to the rate of antro-pyloric pressure waves and inversely related to the rate of isolated pyloric pressure waves. 4. Clearly defined episodes of pulsatile flow produced slightly more than half of the total emptying that occurred. This pulsatile flow was intimately associated in time with antro-pyloric pressure waves. Sequences of isolated pyloric pressure waves were associated with near cessation of emptying. When there were periods of absent pyloric antral pressure waves, flow rates intermediate between the rapid emptying of pulsatile flow during antro-pyloric pressure waves and the near cessation of flow during isolated pyloric pressure waves occurred. 5. The findings suggest a major role for the pylorus in the control of emptying of liquids from the stomach, both as a component of an antro-pyloric peristaltic pump and as a resistor to transpyloric flow during nutrient and hyperosmolar stimulation of duodenal receptors.
Tissue engineering of endothelial cells (EC) and chemical engineering with anticoagulant moieties has been undertaken in order to improve prosthetic graft patency and thrombogenicity. This was done by covalently bonding a compliant poly(carbonate-urea)urethane graft (MyoLink) with arginine-glycine-aspartate (RGD) or/and heparin (Hep) to ascertain whether EC retention could be improved. The retention of these moieties and EC was assessed after exposure to pulsatile flow. We covalently bonded RGD, Hep, and RGD/Hep onto the luminal surface of MyoLink using spacer arm technology. Narrow-beam X-ray photoelectron spectroscopy was carried out to check the efficiency of the bonding. EC were radiolabeled and seeded onto native MyoLink and with 1) RGD-, 2) Hep-, and 3) RGD/Hep-bonded grafts and exposed to shear stress in a physiological flow circuit for 6 h, which reproduces femoral artery flow waveforms and pulsatility. Results were recorded on a gamma camera imaging system. Viability of cells was tested with a modified Alamar Blue assay (ABA) and scanning electron microscopy for morphological appearance of seeded cells. Experiments were repeated (n=6). RGD, Hep, and RGD/Hep were bonded together in a uniform distribution on the luminal surface of each graft type, and bioactivity of each moiety covalently bonded was very high. In the flow circuit, there was exponential cell retention for the first 60 min of flow for all the grafts, but after 6 h of exposure to pulsatile flow the RGD/Hep-bonded graft had a significantly better cell retention rate than native MyoLink (75.7%+/-2.3 vs. 60.5+/-10.1, P<0.05). ABA test showed that all the seeded cells postexposure to flow were viable, and significantly higher metabolic activity was recorded on a RGD/Hep-bonded graft than with MyoLink-seeded graft (P<0.01). Using RGD/Hep covalently bonded onto graft surfaces improves cell retention and provides an antithrombogenic surface for initial blood flow in vivo until full EC activity develops postseeding. This would allow the development and further improvement of hybrid grafts.
The parallel-plate flow chamber (PPFC) with rectangular shape, of which the height is far smaller than its own length and width, is one of the main apparatus for in vitro studies of the mechanical behavior of the cells. Considering that the Reynolds numbers of flows in the usually used PPFCs are small, a perturbation solution of laminar pulsatile Casson fluid in the PPFC is presented using Reynolds number as perturbation parameter. Furthermore, the velocities and shear stresses in the PPFC are given. The numerical results demonstrate that under the same pressure gradient the shear stresses are almost identical between Casson fluid and Newtonian fluid, whereas under the same flux the shear stresses are obviously different between Casson fluid and Newtonian fluid. The results in this paper provide a theoretical way to determine the shear stresses in the parallel-plate flow chamber under pulsatile Casson fluid.
Steady shear stress stimulates transient hyperpolarization coupled to calcium-sensitive potassium (KCa) channels and sustained depolarization linked to chloride-selective channels. Physiological flow is pulsatile not static, and whereas in vivo data suggest phasic shear stress may preferentially activate KCa channels, its differential effects on both currents remain largely unknown. To determine this interaction, coronary endothelial cells were cultured in glass capillary flow tubes, loaded with the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol, and exposed to constant or pulsatile shear stress. The latter was generated by a custom servoperfusion system employing physiological pressure and flow waveforms. Steady shear induced a sustained depolarization inhibited by the Cl- channel blocker DIDS. Even after exposure to steady flow, subsequent transition to pulsatile shear stress further stimulated DIDS-sensitive depolarization. DIDS pretreatment "unmasked" a pulsatile flow-induced hyperpolarization of which magnitude was further enhanced by nifedipine, which augments epoxygenase synthesis. Pulse-shear hyperpolarization was fully blocked by KCa channel inhibition (charybdotoxin + apamin), although these agents had no influence on membrane potential altered by steady flow. Thus KCa-dependent hyperpolarization is preferentially stimulated by pulsatile over steady flow, whereas both can stimulate Cl--dependent depolarization. This supports studies showing greater potency of pulsatile flow for triggering KCa-dependent vasorelaxation.
A numerical simulation of hemodynamics in blood vessels with 0-75% dilation is made. A transient UVP finite element method (FEM) and a stable time integration scheme, based on a predictor-corrector strategy, with constant error monitoring are employed in the flow analysis. The pulsatile flow is analyzed without any assumptions in nonlinear terms and is characterized by thoroughly analyzing the flow, pressure, and stress fields. The central axis velocity, central axis and wall pressures, pressure gradient history, and wall shear stress are influenced by the presence of aneurysm. Time-dependent recirculation regions which are sensitive to the degree of dilation of the vessel are seen in the concavity of the dilation. The transverse velocities and their variations with time are found to be too significant to be neglected. The effects of nonlinear convective terms and the nonlinear geometry of the vessel are clearly depicted through the transverse velocity and pressure profiles.
The lung cancer blood supply originates from the bronchial artery. If vessel signals within pulmonary lesions can be confirmed to be those of the pulmonary artery, color Doppler ultrasound (US) should be able to predict and differentiate benign lesions from lung cancers. Two hundred sixty-four patients with abutting thoracic lesions (including 125 lung cancers and 139 benign lesions) underwent color Doppler US examinations. A pulsatile flow, with the vessel signal length on sonographic appearance > or =1 cm demonstrated by color Doppler US, was arbitrarily defined as a pulmonary artery vessel signal. Of the 264 thoracic lesions, 73 (58%) lung cancers and 107 (77%) benign lesions had detectable color Doppler US pulsatile flow vessel signals. Analyzing the pulsatile flow vessel signals, the color Doppler US pulmonary artery vessel signal was present in 74 (53%) benign lesions, but was found in only two (2%) lung cancers of a specific alveolar cell carcinoma with lobar consolidation. Using the pulmonary artery vessel signal, color Doppler US can be valuable in predicting and differentiating benign lesions from lung cancers (p < 0.0001, sensitivity = 0.53, specificity = 0.98 and positive likelihood ratio 26.5). In conclusion, color Doppler US pulmonary artery vessel signal sign is useful in predicting and differentiating benign lesions from lung cancers.
OBJECTIVE: To study the changes of calcitonin gene-related peptide (CGRP) in patients who underwent total cavopulmonary connection (TCPC) and to assess the effects of non-pulsatile blood flow on the secretion function of the lung. METHODS: Twenty-six patients were divided into 2 groups: study group, 13 patients who underwent extracardiac TCPC, and control group, 13 patients who underwent definitive repair for ventricular septal or atrial septal defect. Blood samples for measurement of CGRP were obtained preoperatively, postoperatively or in the follow-up period. Cardiac index (CI) and pulmonary vascular resistance (PVR) were measured by cardiac catheter. RESULTS: The plasma level of CGRP was significantly higher in the study group than in the control group. CGRP was negatively correlated with PVR (r = -0.99, t = 9.82, P < 0.05), and positively correlation with CI (r = 0.98, t = 6.95, P < 0.05). CONCLUSIONS: After total right heart bypass, the non-pulsatile blood flow in pulmonary circulation may stimulate the lung to secrete CGRP, leading to the decrease of PVR and improve early postoperative recovery.
Osteopontin (OPN) is a noncollagenous component of bone matrix. It mediates cell attachment and activates signal transduction pathways. In this work, bone cells, cultured from fragments of long bones derived from wild-type and OPN-/- ("knock-out") mice, were exposed to pulsatile fluid flow (PFF) over a 60-min period. The medium was assayed periodically for nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release. OPN+/+ cells exhibited a peak of NO production 5-10 min after the onset of PFF, decreasing to a stable plateau at 15 min; much less NO was produced by the OPN-/- cells. PFF resulted in reduced PGE(2) release by both cell types, although the reduction was less for the OPN-/- cells in the 15-30 min window. Both cell types exhibited a similar enhancement of cyclooxygenase2 mRNA levels 60 min after initiation of PFF. These results suggest that bone cells require OPN to respond fully to PFF as assessed by increased NO and reduced PGE(2) synthesis.
Adaptation of saphenous vein, with its intrinsic myogenic tone, from the low-pressure, minimally pulsatile flow of the venous system to the pulsatile flow of the arterial circulation is a minor miracle. Changes in gene expression caused by the pulsatile circumferential deformation (cyclic strain) initiate changes in gene expression, which lead to both vein graft adaptation and pathology. Removal of circumferential deformation by external stenting attenuates the early changes in gene expression and the later development of intimal hyperplasia. Pathways for the transduction of cyclic strain into cellular events have been elucidated in cultured vascular cells. The important second messengers include calcium and reactive oxygen species.
A new Doppler pulmonary artery catheter was used to measure instantaneous and continuous cardiac output in both an in vitro model and in 44 patients undergoing cardiac catheterization. Cardiac output was calculated with use of the Doppler catheter-determined instantaneous space-average velocity and the ultrasonically determined instantaneous vessel area. Doppler flow and thermodilution were compared with electromagnetic flow in the in vitro model and with Fick cardiac output in patients. Doppler catheter-determined flow was highly predictive of electro-magnetic flow in the pulsatile flow model (r = 0.99, slope [m] = 1.01 and SEE = 0.05) and appeared comparable to thermodilution measurements (r = 1.00, m = 1.03 and SEE = 0.02). In patients undergoing cardiac catheterization, Doppler catheter-determined cardiac output appeared to modestly underestimate Fick cardiac output (r = 0.82, m = 0.80 and SEE = 0.09; mean error +/- SEM = -0.26 +/- 0.14 liters/min). However, predictive accuracy was comparable to simultaneously obtained thermodilution measurements (r = 0.85, m = 1.07 and SEE = 0.10; mean error +/- SEM = 0.61 +/- 0.16 liters/min). This new Doppler catheter system utilizes multiple ultrasound transducers to provide angle-independent measurements of vessel diameter and instantaneous velocity within the main pulmonary artery, resulting in a more accurate assessment of Doppler-derived cardiac output. In addition, useful information concerning hemodynamic variables such as peak flow, acceleration, deceleration, stroke work and pulmonary impedance may be derived.
The ultrasound (US) scattered signal from blood has been treated as a random signal by many investigators. However, the degree of randomness of a medium is a relative term that can change considerably with the resolution of the sensor. In this study, the backscattered signal from blood has been looked at as a chaotic signal. By this treatment, according to Taken's theorem, a single variable (e.g., amplitude of the blood-backscattered signal) can be used to reconstruct the nonlinear dynamics of the blood-scattered signal. Multilayer perceptron neural network architecture, with error back-propagation, has been formulated and used as a basis for building and testing the chaotic model of the backscattered signal. This chaotic model is used successfully as a short-term predictor of the backscattered signal from blood-mimicking fluid (BMF) flowing in a vascular flow phantom under pulsatile flow. This modelling approach can be useful, for example, in detecting blood-borne emboli.