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Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes.

A multichannel laser Doppler system has been used to measure microregional fluctuations in perfusion in the HT29 human tumour xenograft and in patients with advanced malignant disease. A comparison is made with previously obtained data for the SaF, a transplantable murine tumour. The 300 microns diameter probes recorded fluctuations in erythrocyte flux in tumour microregions with an estimated volume of 10(-2) mm3. Of the 66 human tumour microregions sampled, 26% showed a change in erythrocyte flux by a factor of 2 or more over the 60 min measurement period, compared with 37% of HT29 and 48% of SaF microregions. In each of the studies more than 50% of changes were completed within 20 min, although slower changes were more common in the human tumours than in the experimental systems. Within the 1 h monitoring period at least 30% of the changes were reversed (human tumours 30%, HT29 45%, SaF 31%). These findings demonstrate that microregional changes in erythrocyte flux, consistent with transient, perfusion-driven changes in oxygenation, are a feature of human malignancies as well as experimental transplanted tumours.

Aged↗

[Significance of the echo-Doppler method in the study of hemodynamic changes of the ophthalmic artery after ligation of the superficial temporal artery].

The authors report the utility of the Echo-doppler and Doppler CW exams before and after the surgical therapy of the chorioretinal and optic nerve's hypoperfusion conditions. They have studied 112 patients affected by these pathologies and evaluated the blood flow's modifications. This exam is even usefull for the patient's selection before surgery without any serious complications.

Adult↗

Are the effects of local joint movement on blood flow limited to the vertebral and internal carotid arteries? Doppler studies of the ulnar artery.

OBJECTIVE: To determine what effect wrist extension has on ulnar artery blood flow. DESIGN AND SETTING: This is a descriptive study performed at a private chiropractic clinic. SUBJECT SELECTION: Sixty-three ulnar arteries were examined from thirty-two volunteers, 15 men and 17 women, whose ages ranged from 21-75 yr. Only wrists that were asymptomatic and freely mobile were candidates for ulnar artery examination. INTERVENTION: The arteries were insonated approximately 2 cm proximal to the pisiform bone using a continuous-wave Doppler flow meter in the neutral position and during passive wrist extension to the limit with the fingers straightened. MAIN OUTCOME MEASURES: The persistence or loss of Doppler signals. RESULTS: Doppler signals from 83% (0.99 confidence interval: 68% < p < 93%) of arteries stopped. In 4% of vessels, the signals were markedly reduced; in 13%, they remained apparently unchanged. CONCLUSION: Blood flow in ulnar arteries can be severely restricted during wrist extension. By using Doppler ultrasound, the ulnar artery may provide a good model of local joint movement effects on arterial blood flow.

Adult↗

Ultrasound and duplex-Doppler in the diagnosis and follow-up of portal hypertension.

Ultrasound examination should be carried out as the first investigation in all patients with suspected hepatobiliary disease. It has a high accuracy in detecting signs of portal hypertension such as ascites, splenomegaly and collateral veins. The most common cause of portal hypertension in the Western world is cirrhosis. Although there is an overlap of ultrasound findings in normal liver, fatty liver, chronic liver disease with and without fibrosis, and cirrhosis, a correct diagnosis of cirrhosis by judgment of ultrasound findings is reported to be achieved in up to 80%. Diagnostic parameters used are size and outline of the liver, its reflectivity and attenuation of the echo-pattern. If used in combination with the Doppler duplex system, the information gained vastly increases. Areas where this technique is able to provide useful and reliable data have been defined in a consensus conference held in Bologna. Doppler flowmetry of hepatic vessels allows detection of presence, direction and characteristics of blood flow. The reliability of the quantitative measurements of blood flow in abdominal vessels is still questioned. When using the same equipment by skilled operators, however, duplex-Doppler data of the portal vein are of value in the assessment of the risk of variceal bleeding, in the evaluation of the progression of liver disease and in the evaluation of medical therapy for portal hypertension. Furthermore, the technique is of practical value in pre-and postoperative examinations for shunt surgery as well as in the pre-procedural work-up of transjugular intrahepatic portosystemic stent shunt (TIPS), during the TIPS procedure and in the post-TIPS followup.

Humans↗

Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma.

PURPOSE: The objective of this study is to evaluate capillary blood flow of the juxtapapillary retina and neuroretinal rim area in primary open angle glaucoma (POAG) by a new noninvasive method performing a high-definition topography of perfused vessels of the retina and the optic nerve head with simultaneous evaluation of blood flow. METHODS: Juxtapapillary retinal and neuroretinal rim area blood flow were measured by scanning laser Doppler flowmetry (SLDF). This new technique is a combination of a laser Doppler flowmeter with a scanning laser system by which the retinal perfusion is simultaneously quantified in 16,000 sites of a retinal area of 2.7 x 0.7 mm. In study I, retinal and optic nerve head blood flow were evaluated by SLDF in 43 patients with POAG and 43 healthy individuals. The mean age of the POAG group was 56 +/- 12 years and of the control group 42 +/- 15 years. In study II, age-matched normals (n = 21) were compared with glaucoma eyes with topical therapy (n = 30) and with glaucoma eyes without topical therapy (n = 16). RESULTS: In study I, the eyes with POAG had an average cup/disc ratio (C/D) of 0.75 +/- 0.20, with an average mean defect of the visual field of 5.3 +/- 5.4 dB. The actual intraocular pressure was 17.8 +/- 4.18 mm Hg in the POAG group and 15.45 +/- 1.82 mm Hg in the control group. For statistical analysis, two age-matched groups of 28 normal eyes of 28 persons with 27 glaucomatous eyes of 27 patients were compared. In normals the blood flow of the neuroretinal rim area was significantly higher than that of the juxtapapillary retinal area (+7.73%, p < 0.01). In POAG both juxtapapillary retinal blood flow and neuroretinal rim area blood flow were significantly decreased compared to an age-matched control group: neuroretinal rim area flow -71% and juxtapapillary retina flow -49%. The decrease of neuroretinal rim area blood flow did significantly correlate with C/D. We found no correlation between reduction of juxtapapillary retinal blood flow and C/D or mean defect. Both glaucoma eyes with and glaucoma eyes without topical therapy showed significant decreased juxtapapillary blood flow compared to normals. We found no significant difference in the juxtapapillary blood flow between glaucoma eyes with and without topical therapy. CONCLUSIONS: In POAG, optic nerve head blood flow and juxtapapillary blood flow were significantly decreased.

Adult↗

Principle, validity, and reliability of scanning laser Doppler flowmetry.

PURPOSE: The objective of this study is to present the reliability and validity of scanning laser Doppler flowmetry (SLDF) performing a high-definition topography of perfused vessels of the retina and the optic nerve head with simultaneous evaluation of blood flow. METHODS: The examination of blood flow by SLDF is based on the optical Doppler effect. The data acquisition and evaluation system is a modified laser scanning device; the wavelength of the laser source is 670 mm, with a power of 100 microW (Heidelberg Engineering, HRF). The reliability of SLDF was estimated by performing five separate measurements in 10 eyes on 5 days. The validity of the method was tested by two experiments. First, in an experimental set-up, the capability of SLDF to measure the velocity of a moving plane in absolute units was estimated. Second, comparative measurements were performed of retinal blood flow in normal eyes and in 33 glaucomatous eyes with SLDF and a commercially available single-point laser Doppler flowmeter (Oculix). RESULTS: We found SLDF to produce a high reliability. The reliability coefficients r1 of flow, volume, and velocity were 0.82, 0.81, and 0.83, respectively. Comparative measurements of the retinal blood flow by SLDF and a single-point laser Doppler flowmeter of corresponding retinal points showed a linear and significant relationship between flow (r = 0.83, p < 0.0001), volume (r = 0.51, p < 0.0001), and velocity (r = 0.59, p < 0.0001). In the experimental set-up, SLDF was able to quantitatively measure velocity in absolute units. CONCLUSIONS: SLDF enables the visualization of perfused vessels of the juxtapapillary retina and the optic nerve head in high resolution by two-dimensional mapping of the optical Doppler shift and a reproducible evaluation of capillary blood flow.

Evaluation Studies as Topic↗

Optic nerve head circulation after topical calcium channel blocker.

PURPOSE: Our purpose was to investigate the effects of the calcium channel blocker verapamil on intraocular pressure and blood circulation in the human optic nerve head. METHODS: The effects of three different concentrations of topical verapamil (0.063%, 0.125%, and 0.25%) on intraocular pressure and optic nerve head capillary blood speed were measured in 12 healthy normal subjects. In a randomized, double-masked design, each subject received one drop of either verapamil or placebo in one eye and the opposite treatment in the fellow eye. Anterior optic nerve circulation was assessed at baseline and 90 min after instillation of the drops using the laser Doppler technique. RESULTS: The intraocular pressure was significantly reduced compared with baseline in both verapamil- and placebo-treated eyes at each concentration. The reductions of intraocular pressure were greater in verapamil-treated eyes (12-17%) than in placebo-treated eyes (9-12%). No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The capillary blood speed in the optic nerve head was increased in both verapamil- and placebo-treated eyes at each concentration, although the only statistically significant increases were with the 0.25% concentration. The mean +/- SEM increase compared with baseline at the 0.25% concentration was 10.4 +/- 3.6% in verapamil-treated eyes (p = 0.017), and 11.6 +/- 4.4% in placebo-treated eyes (p = 0.026). CONCLUSIONS: These results indicate that topical administration of verapamil lowers the intraocular pressure and increases the capillary blood speed in the optic nerve head in normal subjects. Changes measured in verapamil-treated eyes were also observed in placebo-treated eyes, indicating a crossover effect.

Administration, Topical↗

Estimating mechanical blood trauma in a centrifugal blood pump: laser Doppler anemometer measurements of the mean velocity field.

A laser Doppler anemometer (LDA) was used to obtain the mean velocity and the Reynolds stress fields in the inner channels of a well-known centrifugal vaneless pump (Bio-pump). Effects of the excessive flow resistance against which an occlusive pump operates in some surgical situations, such as cardiopulmonary bypass, are illustrated. The velocity vector field obtained from LDA measurements reveals that the constraint-forced vortex provides pumping action in a restricted area in the core of the pump. In such situations, recirculating zones dominate the flow and consequently increase the damage to blood cells and raise the risk of thrombus formation in the device. Reynolds normal and shear stress fields were obtained in the entry flow for the channel formed by two rotating cones to illustrate the effects of flow disturbances on the potential for blood cell damage.

Blood Flow Velocity↗

Coronary microcirculation during left heart bypass with a centrifugal pump.

To estimate coronary microcirculation during left heart bypass (LHB), we performed an experimental comparison study of LHB and intraaortic balloon pumping (IABP). LHB was performed with a BioMedicus BP-80 pump supporting half of the flow of cardiac output whereas the IABP was pumped in a 1:1 mode for cardiogenic shock in a swine model. Coronary circulations were analyzed by electromagnetic flowmeter, pulsed Doppler velocimeter, and laser Doppler flowmeter. Left ventricular end-diastolic pressure (LVEDP) was reduced significantly by LHB. Although there was no significant difference in epicardial flow between the LHB and IABP groups, endo cardial flow was increased significantly by LHB. In the LHB group, the systolic reverse wave of the coronary velocity called a myocardial invalid circulation was reduced remarkably. There was a significant inverse correlation between endocardial flow and LVEDP. These results suggested that LHB was more effective for myocardial microcirculation than was IABP.

Animals↗

Relationship of thallium-201 clearance on exercise stress myocardial scintigraphy to coronary flow reserve in patients with coronary artery disease.

OBJECTIVE: We evaluated thallium-201 (201Th) clearance measurement during exercise myocardial scintigraphy in patients with coronary artery disease, for the assessment of coronary circulatory function and diagnosis. DESIGN: The clearance rate of 201Th was compared with the coronary flow reserve measured by Doppler coronary flow velocimetry. METHODS: We selected 20 patients who had chronic stable angina with single-vessel coronary artery disease of the left anterior descending artery (LAD) and underwent percutaneous transluminal coronary angioplasty (PTCA). Ten control patients had atypical chest pain but no detectable heart disease. Regional net clearance of 201Th was measured from the early and delayed bull's-eye images of 201Th exercise stress single photon emission tomography (SPECT). Using a Doppler catheter, we also measured coronary flow reserve of the LAD, which was obtained by the intracoronary administration of papaverine. RESULTS: The net 201Th clearance in the anterior wall myocardium in the patients with coronary artery disease before PTCA was significantly less than that in the controls. At follow-up angiography after successful PTCA, it increased. The coronary flow reserve before PTCA was also lower than that in the controls. It was increased immediately after PTCA, and was more markedly increased at the follow-up angiography. Before PTCA, regional net clearance in the anterior myocardium was correlated with the coronary flow reserve of the LAD. The ratio for the net clearance of the anterior myocardium at follow-up angiography to that before PTCA was also correlated with the ratio for coronary flow reserve. CONCLUSIONS: In patients with coronary artery disease, the regional 201Th clearance in the ischaemic area measured by exercise 201Th SPECT is correlated with the coronary flow reserve of the affected artery. Moreover, the increase in the clearance rate after PTCA is also correlated with that in the coronary flow reserve. Thus the measurement of regional 201Th clearance might be a useful non-invasive method of estimating of the coronary flow reserve.

Analysis of Variance↗

Role of adenosine in blood flow in the rat intestine.

We examined the relation between adenosine production and increased blood flow. For this purpose, we used a sensor holding system with a laser Doppler blood flowmeter. The elevation of blood flow was observed by administration of adenosine. Therefore, when AMP was administered to the rats, the elevation of blood flow rate was observed. These results suggest that AMP is rapidly transported to the adenosine active site by ecto-5'-nucleotidase.

5'-Nucleotidase↗

Comparison of magnetic resonance imaging and Laser Doppler Anemometry velocity measurements downstream of replacement heart valves: implications for in vivo assessment of prosthetic valve function.

BACKGROUND AND AIM OF THE STUDY: The non-invasive, in-vivo assessment of prosthetic valve function is compromised by the lack of accurate measurements of the transvalvular flow fields or hemodynamics by current techniques. Short echo time magnetic resonance imaging (MRI) may provide a method for the non-invasive, in vivo assessment of prosthetic valve function by accurately measuring changes in the transvalvular flow fields associated with normal and dysfunctional prosthetic valves. The objectives of these in vitro experiments were to investigate the potential for using MRI as a tool to measure the complex flow fields distal to replacement heart valves, and to assess the accuracy of MRI velocity measurements by comparison with Laser Doppler Anemometry (LDA), a gold standard. METHODS: The velocity fields downstream of tilting disc, bileaflet, ball and cage, and pericardial tissue valves were measured using both three-component LDA and MRI phase velocity encoding under a steady flow rate of 22.8 l/min, simulating peak systolic flow. The valves were tested under normal and stenotic conditions to assess the MRI capabilities under a wide range of local flow conditions, velocities and turbulence levels. A new short echo time MRI technique (FAcE), which allowed velocity measurements in stenotic jets with high turbulence, was tested. RESULTS: Good overall agreement was obtained between the MRI velocity measurements and the LDA data. The MRI velocity measurements adequately reproduced the spatial structure of the flow fields. In most cases peak velocities were accurately measured to within 15%. CONCLUSIONS: The results indicate that the FAcE MRI method has the potential to be used as a diagnostic tool to assess prosthetic valve function.

Aortic Valve↗

The use of enzyme activated milk for in vitro simulation of prosthetic valve thrombosis.

BACKGROUND AND AIM OF THE STUDY: Thrombosis remains a serious risk for patients with artificial heart valves and may be attributed in part to adverse blood flow patterns. Although the final assessment of a valve must follow years of clinical experience, in vitro flow analyses give valuable information prior to implantation. Laser Doppler velocimetry and computational fluid dynamics enable quantitative flow analyses to be made in vitro. Whilst these techniques highlight features such as areas of stasis, turbulence and high shear which may predispose to thrombus formation, the complex and time varying nature of the flow through valves makes it difficult to predict accurately potential sites of thrombus deposition and accumulation. METHODS: A technique is described which uses enzyme activated milk as a coagulable blood analogue to indicate flow related clotting. Milk flowing past a test valve or object was activated to clot downstream of the test piece after a certain time period. Milk clot was deposited clot at sites determined by the local flow disturbances. Milk clotting patterns produced on and around standard objects were compared with the transient flow patterns predicted around identical configurations to test the validity of computational flow analyses for predicting flow disturbances leading to clotting. Milk clots on valves were compared with examples of thrombus found on explanted valves of the same design. RESULTS: The sites of deposition were consistent with the predicted flow patterns around the two configurations of flow obstruction studied. Milk clotting patterns on valves corresponded with the early stages of thrombus on explanted valves of the same design. CONCLUSIONS: Whilst a coagulable milk mixture may be used to evaluate the risk of flow induced clot adherence, care must be taken when extrapolating to the clinical situation as other factors such as material properties, blood chemistry and concomitant disease must also be considered.

Animals↗

Prostaglandin E1 ameliorates decreased tracheal blood flow after esophagectomy and aggressive upper mediastinal lymphadenectomy for esophageal carcinoma.

BACKGROUND: Aggressive upper mediastinal lymphadenectomy contributes to a better survival rate after esophageal resection to treat esophageal carcinoma, but it also increases postoperative respiratory complications. Devascularization of the airways because of mediastinal dissection is considered to be a cause of respiratory dysfunction. The present study attempts to clarify whether or not tracheal blood flow (TBF) deteriorates after esophagectomy and, if so, whether or not intravenous prostaglandin E1 (PGE1) attenuates the deterioration. STUDY DESIGN: Patients undergoing esophagectomy and aggressive upper mediastinal lymphadenectomy for the treatment of esophageal carcinoma (EC group, n = 12) or abdominal surgery (control group, n = 6) were enrolled in this study. Measurement of TBF was performed using a laser Doppler flowmeter. Changes in TBF induced by surgery and postoperative intravenous PGE1 were studied in both groups. RESULTS: The TBF deteriorated significantly in the EC group (21.78 +/- 9.60 to 11.24 +/- 4.45 mL/minute/10(-1) kg, p = 0.002) but did not change in the control group (26.13 +/- 6.84 to 26.61 +/- 4.69 mL/minute/10(-1) kg, p = 0.7371). Postoperative intravenous PGE1 partially, but significantly, reversed the deterioration in TBF in the EC group (11.53 +/- 4.58 to 14.87 +/- 6.30 mL/minute/10(-1) kg, p = 0.0207) but did not effect the control group (29.41 +/- 7.89 to 29.41 +/- 8.79 mL/minute/10(-1) kg, p = 0.9989). CONCLUSIONS: Esophagectomy and aggressive upper mediastinal lymphadenectomy cause a deterioration in TBF that is partially attenuated by PGE1.

Alprostadil↗

[Skin circulation--measurements with laser-doppler].

The change in the skin blood flow (SkBF) due to vasoconstriction or vasodilation of the cutaneous vessels is a thermoregulative response during cold or heat stress, respectively. SkBF is estimated in different ways, for instance by measuring body and skin temperature, by venous occlusion plethysmography or by radioactive xenon 133 clearance. The application of laser light based on Doppler shift is a relatively new method for SkBF measurement. At present, several companies operating throughout the world produce laser-Doppler flowmeters. The laser-Doppler method is designed particularly for cutaneous tissues and it facilitates monitoring of the blood flow, however, the measurement results are relative. Depending on the wavelength, the laser light penetrates into the tissue at different depths (from 0.6 to 1.5 mm). The laser light with the wavelength of 632.8 nm enables the measurement of thermoregulative and nutritional blood flow in the skin. The range of the measurement and application of the device provide an opportunity for developing a universal standard. The European Community has published a guide for laboratory quality assurance aimed at improving the standard of measurement records.

Body Temperature Regulation↗

Urinary bladder blood flow changes during the micturition cycle in a conscious pig model.

PURPOSE: To develop a method using laser Doppler flowmetry in conscious pigs, which allows the accurate simultaneous measurement of cystometric and cardiovascular parameters together with changes in vesical blood flow. The animal model was then used to investigate the changes in blood flow in the urinary bladder which occur during the micturition cycle. MATERIALS AND METHODS: Seven large white female pigs were subjected to chronically implanted vascular access and urodynamic catheters as well as an intramural vesical laser Doppler probe. The animals underwent repeated conscious urodynamics with simultaneous measurement of cardiovascular, urodynamic and vesical blood flow parameters. RESULTS: The model shows both compliant and low-compliance behavior and allows greater investigation of the effects of intravesical pressure on blood flow. Blood flow is not altered, during compliant filling and voiding transiently decreases flow to 38% of resting levels, with a rapid return to normal. Low-compliance filling results in a progressive fall in blood flow to a minimum of 45% of normal. At all times an inverse relationship between intravesical pressure and blood flow is maintained. CONCLUSIONS: The pig model proved to be well suited to the experimental conditions and provided reproducible results. The principal determinant of blood flow within the wall of the bladder is the pressure within its lumen. During normal filling the blood supply of the bladder is able to adapt to the large increase in surface area which occurs, maintaining blood flow until the pressure increases.

Animals↗

[Microcirculatory changes in mitral prolapse as an expression of a systemic change in the connective tissue].

Many authors hypothesize that mitral valve prolapse (MVP) can be, in most cases, only a clinical sign of a primitive and systemic disorder of the connective tissue, like in Marfan Syndrome (MS). In our previous works we supported the presence of morphological and functional alterations of the microcirculation in patients affected by MS. In order to characterize a possible common denominator between these pathologies we have studied the cutaneous microcirculation in a group of patients affected by MVP, divided into 2 groups: anatomic MVP (MVP) and MVP syndrome (MVPS). The morphologic parameters have been investigated by nailfold capillaroscopy while digital laser-Doppler was used to study skin flowmetry. The results have been compared with a control group. Capillaroscopic remarkers showed an architecturally disorganized microvasculature with aspects related to a reduced compactness of the microvasculature unit with a significatively higher score compared with controls (7.3 +/- 2.9 vs 3.6 +/- 1 p less than 0.0005). Laser-Doppler flowmetry showed a significatively reduced rest flow; ischemic test showed: spike time 48.9 +/- 36.9 vs 15.3 +/- 7.7 s (p less than 0.0005), hyperemic acme 6.6 +/- 2.7 vs 12.5 +/- 8.4 UP (p less than 0.002); % increase 32.1 +/- 20.2 vs 51.5 +/- 15.4 (p less than 0.002). Thermic test showed a significatively higher thermic acme 8.7 +/- 4.2 vs 12.6 +/- 9.11 UP (p less than 0.05). These results appeared to be correlated with stage pathology as it was observed a severe microvasculature disorders in MVPS. Therefore we suppose that a phenotypic continuum may exist between MS and MVP.

Adult↗