Dynamic Capillaroscopy Research Articles

Deterioration of cutaneous microcirculatory status of Kawasaki disease

Kawasaki disease (KD) is associated with generalized vasculitis with a predilection for coronary artery leading to ectasia and aneurysm in some cases. The aim of this study was to noninvasively assess the cutaneous microcirculation and correlate it with the coronary artery diameter in these patients. Laser Doppler flowmetry and dynamic capillaroscopy were performed at the nailbeds to assess total cutaneous blood flow and microcirculation in children with KD, both in the afebrile phase (after the resolution of fever) and convalescent phases, in comparison to controls. The 100 subjects analyzed in this study included 64 patients with KD (33 in afebrile phase and 31 in convalescent phase) and 36 normal controls. In KD, the capillary morphology was abnormal when compared to controls, with a larger diameter of the arterial and venous limbs, a higher intercapillary distance and a decrease in the loop numbers. Significantly decreased capillary blood cell velocity was noted in afebrile phase but not in convalescent phase. In the afebrile phase, a decreased capillary blood cell velocity significantly correlated with an increased coronary artery diameter. In conclusion, KD patients, both in the afebrile and convalescent phases, exhibited morphologic alterations in the microcirculation when compared to the controls. The results indicate the potential role of dynamic capillaroscopy for the noninvasive survey of microcirculation abnormalities in patients with KD.

Spinal Cord Stimulation: Predictive Parameters of Outcome in Patients Suffering From Critical Lower Limb Ischemia. A Preliminary Study

The aim of our study is to identify the assessment of metabolic and dynamic capillaroscopy parameters that may be predictive of the outcome of spinal cord stimulation in patients affected with non-revascularisable chronic critical limb ischemia. Forty patients, 16 female and 24 male, average age 69 ± 8, underwent microcirculatory screening with transcutaneous oximetry and dynamic capillaroscopy. Microcirculatory assessment was performed before temporary implantation of the spinal cord stimulation stimulator and after one month. The following metabolic parameters were considered: TcPO2-TcPCO2 and with dependent limb, difference between dependent limb and supine values (Δ TcPO2, Δ TcPCO2), change in TcPO2-TcPCO2 after stimulation. Dynamic capillaroscopy parameters were recorded. Follow-up visits were scheduled at three, six, and twelve months after implantation. The procedure was performed placing an Octrode (St. Jude Medical, St. Paul, MN, USA) on the dorsal columns of the spinal cord. Two groups were identified on the basis of transcutaneous oximetry measurements: group A (22 patients) and group B (18 patients), responding differently to the postural test. After one month of home testing period, there was an improvement in metabolic parameters, differing from one group to the other. The morphofunctional data provided by capillaroscopy highlighted the percentage of open capillaries poststimulation as being a significant parameter, although not mentioned in previous studies. Spinal neuromodulation is an effective therapy option in the management of patients affected by non-reconstructable chronic critical limb ischemia.

Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals.

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell velocity (CBV) was measured using dynamic capillaroscopy. During OGT an increase in LDF could be observed at 37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44 degrees C (86%, n.s.). The microvascular response to acetylcholine increased by 164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT investigation. No significant changes in the microvascular measurements could be observed during the water experiment. No significant changes could be observed in the CBV measurements in any phase of the investigation. Plasma C-peptide and insulin levels exhibited an association with the LDF measurements at 37 degrees C (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01). After the ingestion of glucose a sophisticated modulation of microvascular blood flow was found in healthy volunteers. Further studies are necessary to investigate the role of a disturbed postprandial blood sugar control, insulin and C-peptide secretion in the development of microvascular dysfunction, especially in IDDM.

Cyclosporine toxicity in renal transplant recipients detected by nailfold capillaroscopy with Na-fluorescein

Cyclosporine represented a major advance in the medical management of patients with organ transplantation, but its use is limited by the frequent occurrence of hypertension and renal toxicity diagnosed by invasive renal biopsy. Renal histology shows a specific arteriolopathy. It was hypothesized that cyclosporine may also induce subclinical microvascular changes in the skin that might be detected noninvasively by a combination of dynamic capillaroscopy [capillary blood cell velocity (CBV)] with and without intravenous Na-fluorescein (NaF) injection and laser Doppler fluxmetry (LDF). The nailfold skin microcirculation was evaluated in 112 consecutive renal transplant recipients (54 +/- 11 years old; 70 males and 42 females) receiving cyclosporine. The investigation was made the same day as a routine renal biopsy performed in all patients more than two years after transplantation. Renal biopsies were blindly classified as positive (N = 33) when significant specific signs of cyclosporine toxicity were clearly observed (AH2-AH3) and were otherwise negative (AH0-AH1, N = 79) according to the Banff classification. Time to fluorescence peak after NaF injection (tpNaF) was significantly longer in patients with positive biopsies than in patients with negative biopsies (13.9 +/- 8.1 vs. 17.5 +/- 9.4 sec, P = 0.009). All patients but three with negative biopsies (93%) had a tpNaF less than 10 seconds (sensitivity 91%, negative predictive value 93%). On the other hand, CBV, LDF, plasma levels of cyclosporine, and endothelin were similar in the two groups. Nailfold fluorescence capillaroscopy is an accurate and simple mean to rule out cyclosporine toxicity in renal transplant recipients. A normal test could avoid invasive renal biopsy in about 40% of the patients. Renal biopsy would, however, still be indicated when the test is abnormal.

Increased cutaneous blood flow but impaired post-ischemic response of nutritional flow in obese children

It is well known that cardiovascular risk factors and dyslipidemia along with obesity can be identified early in life. Serum lipids and lipoproteins influence skin vessel reactivity in adults. The purpose of this study was to investigate the cutaneous microcirculation and its correlation to dyslipidemia in obese children. Thirty-four obese children and an equal number of age- and sex-matched healthy children were enrolled in this study. Laser Doppler flowmetry and dynamic capillaroscopy were performed to measure total cutaneous blood flow and nutritional blood flow, respectively. A significantly higher cutaneous baseline flow and peak flow after a 1-min arterial occlusion was noticed in obese group as compared to normal control. Results of dynamic capillaroscopy revealed values of resting capillary blood cell velocity that did not differ from controls but a significantly lower peak CBV after a 1-min arterial occlusion in obesity. Plasma lipids examination showed a high triglycerides and low high density lipoprotein cholesterol levels in obesity. Pearson analysis detected no significant correlations between pCBV, baseline flow and peak flow and dyslipidemia in obesity. These results may be explained by the fact that the duration of dyslipidemia in our study population was not long enough to cause vascular damage or the dyslipidemia was not pronounced enough to have an impact on skin vessel activity tests. It is also possible, that the combination of methods used in the present study was not sensitive enough to detect an existing correlations between flow values and high triglycerides/low HDL-cholesterol values in the obese group. Our results suggest that all the responses of the cutaneous microcirculation were mainly due to physiological compensatory rather than pathological reactions in young obese children. The results of cutaneous microcirculatory assessment in obese children provide follow-up parameters for assessing the risk of cardiovascular diseases later in life.

Effects of α-trinositol on peripheral circulation in diabetic patients with critical limb ischaemia. A pilot study using laser doppler fluxmetry, transcutaneous oxygen tension measurements and dynamic capillaroscopy

To evaluate whether alpha-trinositol may have an effect on the microcirculation in patients with diabetes mellitus and critical ischaemia. Ten patients with previously known diabetes mellitus and with critical limb ischaemia were given alpha-trinositol during a 24 h infusion, resulting in a total dose of 2400 mg. Microcirculation was evaluated by means of laser doppler fluxmetry (LDF), transcutaneous oxygen tension (tcPO2) and dynamic capillaroscopy (CBV). Plasma concentration of alpha-trinositol reached a steady state level after 1 h following the start of the administration. There were no detectable changes in blood pressure or heart rate. Laser Doppler flux increased from 41% to 57.5% and tcPO2 changed from 116 to 91 s in "half time recovery" after occlusion. Capillary blood flow showed an increase in resting velocity from 0.1 to 0.5 mm/s at 24 h. The infusion of alpha-trinositol did not cause any changes in the haemodynamics in general, but resulted in changes in LDF(rest value), tcO2(half-time recovery) and CBV(rest flow) during or following the infusion suggesting improved microcirculation.

Use of Dynamic Capillaroscopy for Studying Cutaneous Microcirculation in Patients with Diabetes Mellitus

[is0p9]To investigate the relationship between cutaneous microcirculation and retinopathy in diabetes mellitus, we studied by dynamic capillaroscopy 35 diabetes mellitus patients, including 10 patients without retinopathy, 10 patients with background retinopathy, and 15 patients with proliferative retinopathy. We found that (1) cutaneous and retinal microcirculation in diabetes mellitus in long-term diabetes mellitus, regressional rather than proliferational changes occurred in skin vasculature as compared to that in retina; (2) functional impairments of cutaneous microcirculation, that is, decreased resting capillary blood cell velocity, peak blood cell velocity, and prolonged time to peak capillary blood cell velocity by dynamic capillaroscopy, could be detected in diabetes mellitus patients without retinopathy; (3) the degree of tortouosity of capillaries, impairment in peak capillary blood cell velocity, and time to peak capillary blood cell velocity of cutaneous microcirculation were significantly correlated with the gravity of retinopathy in diabetes mellitus patients; (4) abnormal leakage of fluorescence in cutaneous microcirculation appeared in diabetes mellitus patients with or without abnormal fluorescein angiography in retina. In conclusion, dynamic capillaroscopy used in concert with ophthalmoscopy and fluorescein angiography can facilitate a comprehensive examination of vasculopathy in diabetes mellitus.

Study of Dynamic Microcirculatory Problems in 'Blackfoot Disease' - Emphasizing Its Differences from Arteriosclerosis.

The cutaneous microcirculation can be divided into thermoregulatory shunt vessels and nutritive skin capillaries. Flux in nonnutritional shunt vessels dominates the signal recorded by the laser Doppler flowmeter. Computerized videophotometric capillaroscopy is a sensitive method for assessing cutaneous nutritive microcirculation. Using patients with blackfoot disease and arteriosclerosis as disease models, we evaluated the sensitivity and clinical usefulness of these relatively new techniques for peripheral vascular disorders. In blackfoot disease, blood flux measured by the laser Doppler flowmeter in the affected toe was lower than that in the nonaffected toe. In symptom-free fingers, blood flow was not significantly different between blackfoot disease and arteriosclerosis. However, blood flow in both diseases was lower than that of the control group. Patients who had the same status of thermoregulatory flow and eyeground arteriosclerotic classification underwent a 1-min arterial occlusion of the digits. The postocclusive reactive hyperemia response (PRH) of nailfold capillary loops was evaluated. All parameters for PRH for the cutaneous nutrient microcirculation including resting capillary blood cell velocity (rCBV), peak capillary blood cell velocity (pCBV) and time to pCBV were more significantly disturbed in the blackfoot disease group than in the arteriosclerotic group. On the basis of the results of this study, dynamic capillaroscopy provides a new approach for the early detection of circulatory disturbances resulting from different mechanisms. Copyright 1995 S. Karger AG, Basel

TIME‐DEPENDENT PHOTODYNAMIC DAMAGE TO BLOOD VESSELS: CORRELATION WITH SERUM PHOTOSENSITIZER LEVELS

We have used the technique of dynamic capillaroscopy to study the time-course of photodynamic vascular occlusion in mice injected intraperitoneally with either of two photosensitizers; hematoporphyrin esters (HPE) or meso-tetrahydroxyphenyl chlorin (mTHPC). The peak of vascular occlusion induced by HPE coincided in time with peak serum levels of this photosensitizer (about 3 h after injection). However, there was also a second peak of occlusive activity at about 12 h after injection, at which time serum HPE was falling monotonically. In the case of mTHPC, no peak of occlusive activity was seen at 3 h after injection, even though the serum levels of this photosensitizer, like those of HPE, were highest around this time. Instead, a steady rise in photosensitizing activity was observed, peaking at 11 h. This decoupling between serum drug levels and vascular photosensitization--partial for HPE and complete for mTHPC-suggests that direct photosensitization of endothelial cells is unlikely wholly to explain the vascular collapse. Instead, there must be either another compartment that accumulates photosensitizer more slowly and in which photodynamic activity has an indirect effect on the blood capillaries or a slow metabolic transformation of mTHPC into a more active sensitizer.

Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease.

Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD). Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation. Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD.

An evaluation of skin capillary blood flow determinations in neonates using a computerized videophotometric method

Dynamic capillaroscopy has been shown to give valid measurements of skin capillary blood flow in adults. The aim of this investigation is to evaluate the accuracy of the method when applied to studies in newborn infants. A computerized videophotometric technique was used to measure the skin capillary blood cell velocity (CBV) and the capillary erythrocyte column diameter at 64 standardized locations in 16 nailfold capillaries in five subjects. To estimate the method's reliability, we calculated the coefficient of variation (CV = 1 SD/mean × 100%) for repeated measurements at each location. The CV for CBV determinations was found to be 3.4% (0.9–13%) and the corresponding value for capillary diameter measurements was 6.7% (0.5–12%) (median and range). Although the CBV and diameter values were found to vary along the course of the capillary, the volume flow of blood cells was assumed to be the same in simultaneously studied but different sections of the capillary. The paired CBV and diameter observations were therefore used to calculate blood cell flow values at an average of four different intracapillary locations. To estimate the method's validity, the CV for these repeated flow calculations was determined and found to be 7.5% (3.2–26%). We conclude that the age-specific characteristics in neonates, mainly a high hematocrit and short, irregular skin capillary loops, do not limit the feasibility and accuracy of videophotometric microscopy for dynamic microcirculatory studies in neonates.

Microcirculatory methods for the clinical assessment of hypertension, hypotension, and ischemia.

New techniques are now available for studying skin microcirculation non-invasively in humans. The clinically most useful ones are laser Doppler flowmetry, vital capillaroscopy, dynamic capillaroscopy and fluorescence microscopy. Some of these techniques have now been used in clinical practise for studying the reactivity of the skin microcirculation in patients with hypertension, hypotension and ischemia. It was found that the reactivity to stress in patients with hypertension can be quite different in the skin microvascular bed as compared to the total circulation of the region. In patients with local hypotension due to an arterial obstruction the postocclusive reactive hyperemia response is significantly changed compared to normals. The vasomotion activity is also decreased in the low pressure area. A marked decrease in the local blood pressure may lead to tissue ischemia. In these patients the risk of skin necrosis can be evaluated by microscopic classification of the structural changes of the capillaries in the area of ischemia. When the skin capillaries are void of erythrocytes the risk of necrosis is imminent.

Dynamics of Skin Microcirculation in Humans

The human cutaneous microcirculation has so far been studied by rather crude methods, such as plethysmography and 133Xn clearance. New sophisticated and noninvasive techniques are now available, with which the microcirculation of the skin can be continuously studied and measured for hours. With two such methods, i.e., Laser-Doppler flowmetry and dynamic capillaroscopy, fast dynamic fluctuations of the microcirculation can be followed. Under resting conditions, the total skin flow of a small area (1-2 mm2) varies consistently with time. These variations are caused by the arterial pulse, but also by active vasomotion with a frequency of about 4-8 cycles/min. These fluctuations can also be seen in single skin capillaries, but with a somewhat faster frequency: 6-10 cycles/min. The reaction of the cutaneous microcirculation to provocation tests, such as postocclusive reactive hyperemia response and venous occlusion (50 mm Hg), can also be studied. The time to peak during postocclusive reactive hyperemia is very consistent. In response to venous congestion, capillary flow rate falls drastically, whereas Laser-Doppler flow is much less dramatically reduced. These discrepancies suggest that the Laser-Doppler flowmeter records blood flow in skin vessels in addition to the superficial, nutritional capillaries. The dynamic pattern of the skin microcirculation is altered in patients with hypertension, diabetes, and obstructive arterial disease.

Vital capillary microscopy for assessment of skin viability and microangiopathy in patients with diabetes mellitus.

Vital capillaroscopy is useful in clinical practice to study the nutritional skin capillaries and for evaluating the risk for skin necrosis in patients with peripheral ischemia. This method is especially valuable in the investigation of patients with diabetes mellitus (DM) in whom the arterial inflow to the foot can be almost normal despite the development of skin necrosis due to impaired nutritional circulation. When the capillary morphology in the feet of asymptomatic diabetic patients was investigated, significantly more areas with widely dilated capillaries were present both in insulin and tablet treated patients compared to controls. By using dynamic capillaroscopy the flow velocity in skin capillaries can be determined under physiological conditions. Fourteen diabetic patients were compared with matched non-diabetic controls. The capillary blood flow during resting conditions was equal in the two groups but a delay in the postocclusive reactive hyperemia response was seen in the diabetic patients. The reason for this may be a vasomotor dysfunction in the precapillary arterioles or an increased blood viscosity. Further studies using dynamic vital capillaroscopy may improve our knowledge of the complex mechanisms responsible for diabetic microangiopathy.