Digital blood flow measurement by venous occlusion plethysmography in Raynaud's phenomenon. Value of the rewarming test

The fingertip blood flow measured by mercury strain gauge plethysmography with venous occlusion, at 22 degrees C room temperature, had significantly lower mean values in 190 patients with Raynaud's phenomenon (55 men aged 49 yrs +/- 16, 135 women aged 48 yrs +/- 16) than in 40 age and sex matched controls: 18 ml/100 ml/minute +/- 14.6 versus 35 ml/100 ml/minute +/- 15 at level p less than 0.01. The mean fingertip blood flow was significantly lower (p less than 0.01) in 31 cases of scleroderma and 32 cases of pulpar necrosis (respectively 13 ml +/- 13 and 11 ml +/- 8) than in 55 cases of primary Raynaud's disease (no detectable etiology and normal capillaroscopy 5 years after onset) or in 34 cases of mild Raynaud's phenomenon (respectively 21.6 +/- 16 and 24.4 +/- 18). A warming test (both hands in water at 45 degrees C during 3 minutes) was performed in 50 cases with low basal fingertip blood flow. It induced a "normalized" flow in 22 cases (mostly primary or mild Raynaud), a partly improved flow in 20 cases (mostly secondary Raynaud) and no improvement in 8 cases (scleroderma). The warming test appears to be clinically useful to assess the vasospasm and the vasodilating capabilities.     

Correlations among capillaroscopic abnormalities, digital flow and immunologic findings in patients with isolated Raynaud's phenomenon. Can laser Doppler flowmetry help identify a secondary Raynaud phenomenon?

Thirty subjects with a diagnosis of isolated Raynaud's phenomenon, according to anamnestic and objective criteria, were cross-evaluated by various methods: laser Doppler flowmetry (LDF) during a standardized cold and rewarming test, nailfold capillaroscopy, immunological and other laboratory parameters, to assess the diagnostic and prognostic significance of each method. Correlations were also assessed among disease duration, capillaroscopic pattern score, quantitative digital flow values and laboratory parameters. Nearly 30% of patients showed immunologic abnormalities (ANA positivity at variable titres, ENA, hypocomplementemia, immunocomplexes); 16% of patients had a pathologic capillaroscopic pattern, not well correlated with immunologic findings; a characteristic cold stop reaction of digital flow (partial or total) was detected in 86% of the subjects; in ANA+ pts., ANA titers were positively correlated with the intensity and length of stop reaction (Trec). A significant correlation between digital flow parameters and the capillaroscopic score was also found in each considered group. Our results outline the relevance of LDF, during a standardized thermic test, to evaluate apparently primary RP, because even if a definite scleroderma-like capillaroscopic pattern is absent, this flowmetric method may detect potentially secondary RP patients.     

Measurement of colonic blood flow with laser Doppler flowmetry

Colonic blood flow was measured with laser Doppler flowmetry during operation in 62 patients and during coloscopy in 15 patients. In 18 subjects mucosal and serosal laser Doppler signals were compared during 'resting' conditions, vascular occlusion, and reactive hyperemia. The mucosal (n = 36) and serosal (n = 36) flowmeter signals were of the same order of magnitude throughout the whole range of flowmeter signals (r = 0.96; p less than 0.001). In eight subjects total venous outflow from a colonic segment was measured simultaneously with flowmeter recordings from the serosal side. A correlation coefficient of 0.95 (n = 46; p less than 0.001) was obtained between total intestinal blood flow and serosal flowmeter signal during 'resting' and reduced blood flows. In this flow range a calibration curve was constructed for interpretation of the flowmeter signals in absolute flow units. The wall thickness of the bowel determined the quantitative relationship between flowmeter signal and total intestinal blood flow. It is concluded that laser Doppler flowmetry represents a potentially very interesting non-invasive, continuous method for the quantitative study of human intestinal blood flow.     

Assessment of gastric blood flow with laser Doppler flowmetry

The use of laser Doppler flowmetry (LDF) to measure gastric blood flow was evaluated in the cat and man. The reproducibility of laser Doppler flowmetry recordings was studied in the feline stomach. In five cats flowmeter signals and venous outflow of the stomach were simultaneously recorded. The flowmeter recordings were made during operation and gastroscopy in 140 patients by means of two different (PF1-4-kHz and PF2-12-kHz) laser Doppler systems. The flowmeter recordings were highly reproducible during the cat experiments, with a coefficient of variation varying between 4% and 13%. Angulation of the probe within 60-120 degrees against the tissue under study did not affect the flowmeter signal. Pressure of the probe against the studied tissue attenuated the flowmeter signal 42 +/- 13% (n = 10). A significant correlation coefficient (r = 0.76; p = 0.01; n = 30) was obtained between flowmeter signal and venous outflow of the stomach. In man the PF2-12-kHz system yielded a higher flowmeter signal (14.5 +/- 6.9 V; 32 patients) than the PF1-4-kHz system (7.9 +/- 2.5 V; 108 patients). Flow dimensions were calculated by using results previously obtained in the intestines. The estimated blood flow values amounted to 31 +/- 10 and 57 +/- 27 ml min-1 100 g-1 for the PF1-4-kHz and PF2-12-kHz systems, respectively. In conclusion, laser Doppler flowmeter is a promising technique for studying gastric perfusion during operation and endoscopy. Motion artifacts are the major drawback of the present laser Doppler systems.     

Digital blood flow and nailfold capillary microscopy in Raynaud's phenomenon

Digital blood flow was assessed by photoplethysmography, ultrasonic arterial flow tracing and measurement of systolic blood pressure, and compared to nailfold capillary microscopy in 20 normal controls, 16 patients with primary Raynaud's phenomenon, 40 with undifferentiated connective tissue disease and 30 with systemic sclerosis. All 4 measurements showed significant differences between controls, Raynaud's phenomenon and systemic sclerosis but only capillaroscopy (mean number of enlarged capillary loops and avascular score) was able to differentiate between primary Raynauds and undifferentiated connective tissue disease. Capillaroscopy (mean numbers of enlarged capillary loops) was the most sensitive (100%) and specific (81%) test with a positive predictive value of 90% for systemic sclerosis.     

Gastric blood flow in patients with gastric ulcer measured by endoscopic laser Doppler flowmetry

Gastric blood flow has been studied endoscopically by laser Doppler flowmetry in 15 patients with chronic gastric ulcer. In all patients the ulcer was located at the lesser curvature of the corpus. The blood flow measured in this area was decreased compared with healthy controls, whereas the flow values in other parts of the stomach were similar to those of controls. In the ulcer bed very low blood flow values were measured. The blood flow of the ulcer margin was similar to that of other parts of the lesser curvature. After 4-6 weeks' treatment with the H2-receptor antagonist cimetidine, the ulcer was healed in about 70% of the patients. The blood flow measured at the lesser curvature and in the ulcer area was still low and of the same magnitude as the corresponding values of the first measurement. After 4 months the ulcer was healed in all but one patient. The blood flow of the lesser curvature had increased significantly, whereas decreased blood flow was measured at the distal part of the greater curvature. In the area where the ulcer was located, very low flow values were still measured. This finding may explain why ulcer recurrence usually occurs at the site of the primary ulcer.     

Assessment of blood flow in the small intestine with laser Doppler flowmetry

Blood flow in the small intestine was assessed in 48 patients by laser Doppler flowmetry. Mucosal and serosal flowmeter signals were compared during 'resting' conditions, vascular occlusion, and reactive hyperemia. Serosal flowmeter recordings were compared with the total blood flow of a bowel segment as measured by venous collection. The magnitudes of the mucosal (n = 49) and serosal (n = 49) flowmeter signals were comparable throughout the whole range of flowmeter signals (r = 0.97; p less than 0.001). A correlation coefficient of 0.95 (n = 51; p less than 0.001) was obtained between serosal flowmeter signals and total blood flow during 'resting' and reduced blood flows. During vasodilatation after a vascular occlusion, blood flow was underestimated by the flowmeter. A calibration curve could be constructed for approximate interpretation of the flowmeter signals in absolute flow units. The present study underlines the potential of laser Doppler flowmetry in the assessment of blood flow in the human small intestine.     

Gastric mucosal blood flow in portal hypertension patients--a laser Doppler flowmetry study.

Gastric mucosal blood flow was evaluated endoscopically by means of laser Doppler flowmetry in an attempt to explore microcirculatory changes in different areas of gastric mucosa in portal hypertension patients as compared with controls. Twenty male--Child B--cirrhotics and seven healthy subjects were assessed, the recordings being performed at ten defined points of the stomach. Statistical evaluation revealed that blood flow in the body of the stomach was decreased in cirrhotics. Bearing in mind that congestive gastropathy, found mainly in the gastric corpus, is due to changes in gastric vascularity leading to congestion and stasis, we consider that the decrease in gastric mucosal blood flow may be attributable to these vascular alterations.     

Comparison of blood flow measurements by hydrogen gas clearance and laser Doppler flowmetry in the rat duodenum

This report examines the relationship between hydrogen gas clearance and laser Doppler flowmetry measurements in the duodenum of fasted, anesthetized rats under conditions of 1) reduced perfusion due to graded levels of hemorrhagic hypotension or 2) hyperemia due to perfusion with step doses of acid. There was a significant correlation between hydrogen gas clearance and laser Doppler flowmetry measurements (r = 0.73, p less than 0.01; n = 32 data points in 16 rats). The change in laser Doppler flowmetry values from the period immediately before to the period during the 3 min of acid perfusion was significantly correlated with the dose of acid used (r = 0.51, p less than 0.01; n = 27 rats). The changes in hydrogen gas clearance and laser Doppler flowmetry values from the 30-min period before to the 30-min period after acid perfusion were not correlated with the dose of acid used (r = 0.30 and 0.33, respectively). We conclude that in the rat duodenum 1) the significant linear correlation between hydrogen gas clearance and laser Doppler flowmetry when blood flow is reduced suggests that the countercurrent exchange mechanism is unlikely to modulate significantly hydrogen gas clearance measurements, and 2) the dose-related acid-induced duodenal hyperemia is transient rather than persistent when the rat duodenum is exposed to hydrochloric acid (0.03 to 0.1 N) for 3 min.     

Repeated measurement variation and precision of laser Doppler flowmetry measurements.

The repeated measurement variation of laser Doppler flowmetry (LDF) recordings is essential for the precision level of the method in the assessment of tissue perfusion. The objective of this paper was to discuss the practical consequences of this problem by presenting a statistical method which can be used to estimate the number of replicates needed to reach a certain precision standard. By a repeated measures analysis of variance with a single-factor design, the mean variation of repeated measurements and its standard deviation were estimated. This estimate was used for simulation of a 95% confidence interval with length defined as a percentage of the mean of repeated measurements. The analyses were made in LDF samples performed in skin, gastric mucosa, and pig kidney in order to exemplify the use of the method. Paired values gave an unacceptable precision estimate in all tissues, but by increasing the number of replicates, the estimated precision was greatly enhanced. A preliminary recommendation for the practical use of LDF in the assessment of tissue perfusion is to perform at least four to six repeated measurements. Further studies are needed in order to establish methodological standards. The presented statistical considerations could also be relevant for other procedures used in microvascular research.     

Evaluation of skin blood flow and venoarteriolar response in patients with diabetes and peripheral vascular disease by laser Doppler flowmetry

Skin blood flow in the distal foot was evaluated in patients with peripheral vascular disease and diabetes and compared with skin blood flow in normal volunteers by use of laser Doppler flowmetry. Resting blood flow (RBF) and standing blood flow (SBF) were recorded in a room at a constant temperature (20-22 degrees C). The RBF was found to be different in the five groups (normal, diabetics, patients with intermittent claudication, those with rest pain and those with impending gangrene. In diabetics RBF was significantly higher than in normal subjects. Even on standing, SBF in diabetics was higher and not different from RBF, indicating an ineffective venoarteriolar response (VAR). The VAR was also reduced in patients with claudication and was abolished in patients with rest pain and impending gangrene. In patients with rest pain SBF was increased. Laser Doppler flowmetry is a useful technique for evaluating skin perfusion in patients with peripheral arterial disease and for discriminating among different classes of patients.     

Evaluation of laser Doppler flowmetry in the assessment of intestinal blood flow in cat

Laser Doppler flowmetry with a differential detector system has been used in the assessment of blood flow in the feline small intestine. Simultaneous mucosal and serosal laser Doppler flowmeter recordings were compared with total blood flow of a bowel segment measured by an optical drop-recorder unit in 6 cats. Blood flow through the muscularis layer was estimated using the 85Kr washout technique. A correlation coefficient of r = 0.96 (mucosal recordings = 90, serosal recordings = 80, p less than 0.001) was obtained between laser Doppler flowmeter output signals and total blood flow at different levels of vascular tone, regardless of whether the flowmeter recordings were made from the mucosal or the serosal side of the bowel wall. At intense vasodilation, the flowmeters showed a tendency to underestimate blood flow. The flowmeter signals were at variance with the muscularis blood flow but were clearly correlated to the calculated mucosal-submucosal blood flow. The uneven blood flow distribution in the intestinal wall did not affect the ability of the flowmeters to reflect total blood flow from either side of the bowel wall. A calibration curve could be constructed for approximate interpretation of the laser Doppler signals in absolute flow units. However, further experiments in humans and further development of the technique must be performed to elucidate clinical applications of the method.     

Skin blood flow in patients with systemic sclerosis and Raynaud's phenomenon: effects of oral L-arginine supplementation.

OBJECTIVE: To measure skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in the digits of patients with systemic sclerosis (SSc) and control subjects. Additionally, to test the effects of oral L-arginine supplementation versus placebo in patients. METHODS: Skin blood flow was measured at the dorsum of the finger using laser Doppler flowmetry during iontophoresis of endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators. L-arginine and placebo supplementation were given in a double blind, crossover fashion (8 g daily for 28 days). RESULTS: In comparison to control subjects, dose dependent vascular responses to acetylcholine were diminished in patients with SSc (1.7 +/- 0.3, 3.6 +/- 0.7, 5.9 +/- 1.5 vs 1.4 +/- 0.1, 2.4 +/- 0.6, 2.4 /- 0.5; p < 0.01, ANOVA). Vascular responses to sodium nitroprusside were not significantly different between control subjects and SSc patients. L-arginine supplementation, however, had no significant effect on vascular responses to acetylcholine and sodium nitroprusside. CONCLUSION: There is an abnormality of endothelial dependent vasodilatation in the digital vasculature of patients with SSc. The lack of effect of supplementation with L-arginine suggests the abnormality may be independent of the L-arginine/nitric oxide pathway and may involve prostanoids.     

Effect of pentagastrin and cimetidine on gastric blood flow measured by laser Doppler flowmetry

Endoscopic laser Doppler flowmetry has been used to study the effect of the secretagogue pentagastrin and the H2-receptor antagonist cimetidine on gastric blood flow in 24 healthy subjects. The subcutaneous injection of pentagastrin, 0.6 micrograms/kg body weight, caused a significant increase in gastric acid secretion. This increase did not provoke any significant change in gastric blood flow, measured in seven defined areas of the oesophagus and stomach. Furthermore, no significant correlation was found between the level of basal and maximal acid secretion and blood flow. The infusion of 200 mg cimetidine caused a significant reduction of gastric blood flow in five of the seven investigated areas (P less than 0.05 and P less than 0.01). Cimetidine had no effect on blood pressure or skin blood flow, measured by laser Doppler flowmetry. The study was performed without previous stimulation of acid secretion, and blood flow reduction was measured in both the corpus and the antrum of the stomach. The effect of cimetidine is therefore hardly a result of the acid-reducing effect of the drug. In this study no significant relationship could be shown between the gastric wall blood flow and acid secretion.     

Digital flow exploration by color Doppler ultrasound in patients with Raynaud's disease or systemic sclerosis

BACKGROUND: Raynaud's phenomenon (RP) is a frequent vascular paroxysmal syndrome of the extremities. Generally benign, the condition is called Raynaud's disease (RD), which may reveal a connective tIssue disease, particularly systemic sclerosis (SS). We evaluated digital blood flow in patients with RD and SS using color Doppler ultrasound. PATIENTS AND METHODS: Ultrasound examination was performed with a newly developed multi-D linear array transducer (VFX 13-5 Siemens), which allows better resolution. We first measured the diameters of the digital arteries (appendix 1) then epidermal, dermal, and hypodermal thickness for each patient (appendix 3) and performed a qualitative and quantitative analysis of pulpar microcirculation (appendix 4 & 5). All measures were made at 25 degrees C, 45 degrees C, 11 degrees C and after recovery. Thirty-three patients were included: 14 with primary RD and 19 with SS as assessed by American College of Rheumatology criteria. RESULTS: The diameters of the digital arteries showed significant discrepancies allowed to distinguish primary RP from SS. At 11 degrees C, diameters were 0.6 +/- 0.2 mm for primary RP versus 0.2 +/- 0.3 mm for SS on lateral digital arteries (LDA) [p=0.005]; 0.7 +/- 0.2 mm for primary RP versus 0.4 +/- 0.3 mm for SS on medial digital arteries (MDA) [p=0.004]. After recovery, these diameters were respectively 1 +/- 0.2 mm versus 0.5 +/- 0.4 mm for LDA [p=0.000] and 1 +/- 0.2 mm versus 0.6 +/- 0.3 mm for MDA [p=0.000] (tables 1, 2, 3, 4). Similarly, pulpar vascularization was significantly higher in primary RP than in SS (tables 6, 7, 8). No difference was found in skin thickness nor in the epidermal aspect between the two groups (table 5). CONCLUSION: Color Doppler ultrasound shows morphological and dynamic differences between RD and SS.     

Evaluation of endoscopic laser Doppler flowmetry for measurement of human gastric blood flow. Methodologic aspects

Endoscopic measurement of gastric blood perfusion by laser Doppler flowmetry (LDF) has been evaluated in 28 patients and 15 healthy volunteers. During the recordings it was necessary to keep the probe in light contact with the mucosa to obtain stable curves and to avoid artificial Doppler signals caused by relative movements between the gastric wall and the probe. Gastric distention by air insufflation did not influence the recorded flow level significantly when air insufflation was moderate. The intravenous injection of 0.6 mg atropine did not cause any significant alteration in recorded blood flow, and this drug may be used as premedication before endoscopic blood flow measurements. Recordings with both 4- and 12-kHz bandwidth of the LDF instrument showed a relative constant relationship for different flow levels, the flow values measured with 12 kHz being about twice the corresponding values measured with 4 kHz. With 12-kHz bandwidth more of the disturbance signal is recorded, which makes analysis of endoscopic recorded flow curves difficult and inaccurate. It is therefore recommended to use 4-kHz bandwidth during endoscopic measurements in conscious humans. Blood flow measurements from both sides of the gastric wall were consistently of the same order of magnitude (r = 0.91), and the endoscopically recorded output signal increased in three of five patients when a reflecting mirror was placed at the serosal side. The results indicate that endoscopic LDF usually represents blood perfusion in all layers of the gastric wall.     

Comparison of thermography and laser Doppler imaging in the assessment of Raynaud's phenomenon

The main objective of the study was to compare the techniques of thermographic and laser Doppler imaging in the assessment of digital blood flow. Thermography measures surface temperature; laser Doppler measures microciculatory flow. Seventeen healthy control subjects and 40 patients with Raynaud's phenomenon (7 primary, 33 secondary to systemic sclerosis) underwent a 20-min acclimatization period at 23 degrees C. Thermographic and then laser Doppler images were taken of the dorsal aspect of both hands, and the procedure was repeated at a room temperature of 30 degrees C. Three regions/values of interest from each hand were chosen for analysis: the dorsum of the hand, the tip of the middle finger, and the "gradient" between these. Thermographic and laser Doppler results correlated poorly. For example, correlations between techniques for the gradient value were as follows: left hand 23 degrees C, r = 0.61; right hand 23 degrees C, r = 0.64; left hand 30 degrees C, r = 0.47; right hand 30 degrees C, r = 0.48. One explanation for these findings is that laser Doppler imaging is more sensitive to blood flow changes and therefore more likely to show inhomogeneities than the highly damped temperature response. Therefore one technique cannot substitute for another.     

Portal vein blood flow measurements using pulsed Doppler and electromagnetic flowmetry in dogs: a comparative study

Comparative measurements of portal vein blood flow were performed at laparatomy in anesthetized dogs using either a pulsed Doppler echo system or electromagnetic flowmeters. Three hundred four simultaneous determinations were obtained under baseline conditions and during vasopressin and glucagon infusions. In each dog, serial triplicate measurements were taken within 10 min of each other. In all the cases, flow changes induced by vasoactive drugs followed the same direction regardless of the method used. Portal vein blood flow as measured by electromagnetic flowmetry ranged from 85 to 1570 ml/min. Portal vein blood flow values obtained with Doppler and electromagnetic flowmeters were not significantly different (609 +/- 335 vs. 600 +/- 370 ml/min; p = NS) and were highly correlated (r = 0.918, p less than 0.001). The difference between values obtained by the two techniques was -3 +/- 159 ml/min or -1.0% +/- 21.2% (mean +/- SD). This difference was not influenced by the portal vein diameter but increased slightly as a function of the angle of insonation. When considering the mean of triplicate measurements, we also found a highly significant correlation between data obtained by the two techniques (r = 0.934, p less than 0.001; n = 63). The mean difference was 11 ml/min, but limits of agreement between these methods were -267 and +239 ml/min. This relative discrepancy was explained by a coefficient of variation higher in Doppler measurements than in electromagnetic measurements (10.9% vs. 5.9%). These data demonstrate that under our experimental conditions, Doppler flowmetry is probably not an ideal method to measure absolute portal vein blood flow values, and that more sophisticated equipment is needed to improve its reproducibility and accuracy. In humans, however, this method might be a useful tool to assess the direction of portal flow changes in the same individual.