Vital Capillary Microscopy Research Articles

Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial.

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.

Micro- and macrocirculatory effects of apheresis in patients with familial hyperlipidemia.

High lipid levels have been shown to coexist with a disturbed vascular endothelial function. Thus, acute lipid lowering could be expected to improve vascular reactivity. Patients with familial hyperlipidemia (FH) have substantial and rapid decreases in lipid levels after low-density lipoprotein apheresis. Thus, an opportunity exists to study acute effects of lipid lowering on vascular reactivity. Flow mediated vasodilation (FMD) is commonly used to assess endothelial function in conduit vessels, whereas vital capillary microscopy during the post-reactive hyperemia (PRH) phase is used to assess response at the microvascular level. It is not known whether endothelial dysfunction is a general phenomenon in all kinds of vessels or if there are differences between micro- and macrovessels. In the present study, we were not able to demonstrate an improved vascular response after acute lipid lowering in FH patients. This was true both in the microcirculation (PRH) and in the conduit vessels (FMD). However, the two methods gave concordant results, demonstrating disturbed vascular reactivity in the patients as compared with healthy subjects. We have found no previous report with parallel assessments at the microcirculatory and macrocirculatory levels.

N-acetylcysteine improves microcirculatory flow during smoking: new effects of an old drug with possible benefits for smokers.

Cigarette smoking provokes marked acute changes in the microcirculatory vasculature, including a reduced blood flow velocity. In accordance with the hypothesis that the reduced blood flow is due to an imbalance between pro-oxidants and oxidants, we recently showed that most of the reduction could be reversed by a high dose of vitamin C. In the present work we tested the hypothesis that N-acetylcysteine, a mucolyticum and an antioxidant, may have an effect on the smoking-induced changes observed by vital capillary microscopy of the nailfold. In all, 37 healthy volunteers of both genders and with varied smoking habits were treated with N-acetylcysteine 200 mg t.i.d. for 2 weeks. In vivo investigation of the microcirculation by capillaroscopy was performed before and after treatment. Treatment with N-acetylcysteine significantly reduced the smoking-induced relative decrease in capillary blood flow velocity in a group of volunteers with varied smoking habits (p = 0.0016). The preventive effect was clearly significant in smokers (p = 0.003). Treatment with N-acetylcysteine has a positive impact on microcirculatory flow during smoking, particularly in habitual smokers.

Vital capillary microscopic findings in the nailfold of patients with diabetes mellitus.

Preliminary investigation done in 100 healthy adults and 20 healthy children had shown that the interpretation of significance of changes in capillary morphology need to be corrected, since capillary changes previously considered to be pathological are also to be found in large numbers in healthy subjects. Against this background, the question has now been investigated whether the capillary microscopic findings in diabetics deviates from those found in normals, and whether the duration of the diabetes, its treatment, its sequelae, or concomitant diseases have any influence on the capillary microscopic appearance. In 100 patients aged between 44 and 88 years with type 2 diabetes vital capillary microscopy was carried out on all ten fingers in the usual manner. The evaluation of the video recordings was done only when all the examinations had been completed--by two examiners blinded to the clinical data. It was shown that 66% of the patients demonstrated pathological capillary microscopic findings. These findings included pathologically increased apical and non-apical dilatations (32%), haemorrhagic extravasations (20%) and branchings (45%). No differences were found between the therapy groups (insulin--oral medication) nor was any relationship between the appearance of capillary changes and the duration of diabetes observed. Diabetics with concomitant diabetic sequelae (polyneuropathy), demonstrated no differences in capillary morphology as compared with diabetics with no such sequelae. Diabetics are found to have an increased incidence of pathological capillary morphology taking the form of increased apical dilatations, branchings and haemorrhagic extravasations. Neither the treatment, nor the duration of the illness, nor diabetic sequelae appeared to have any influence on the capillary microscopic changes.

A Single High Dose of Vitamin C Counteracts the Acute Negative Effect on Microcirculation Induced by Smoking a Cigarette

Cigarette smoking is associated with marked acute changes in microcirculation including reduced blood flow. We tested the hypothesis that the reduced blood flow velocity is due to the imbalance between prooxidants and antioxidants that occurs as a consequence of smoking and that it can be reduced by an antioxidant. The effect of smoking a single cigarette on nail-fold microcirculation was analyzed in 24 healthy subjects with varying smoking habits. Vital capillary microscopy was used and the blood cell flow velocity in the capillaries was evaluated before and 1–30 min after smoking. Smoking induced a marked decrease in microcirculatory blood flow in 23 of the 24 subjects (40–50% decrease 1–5 min after smoking). This change was reduced by more than 50% in the same subjects after intake of 2 g of vitamin C 2 h before smoking (P < 0.000l by ANOVA test) with smokers responding similarly to nonsmokers in these experiments. Intake of 1 g of vitamin C had no significant effect on the smoking-induced changes in most of the subjects tested (n = 11). Pretreatment with aspirin had little or no effect on the response to smoking (n = 9). Our results show that treatment with a single high dose of vitamin C can reduce and in some individuals even completely abolish the negative acute effect on microcirculation induced by smoking a single cigarette. This effect of vitamin C is not likely to be mediated by the cyclooxygenase system.

Vital Capillary Microscopy of Skin Areas at the Forefoot of Diabetic Patients using Intraarterial Injection of Na-Fluorescein

A modified technique of vital capillary microscopy with intraarterial application of Na-fluorescein has been introduced in the study of nutritional skin microcirculation to assess skin microcirculation of different diabetic patients, comprising one group without neurocutaneous complications (group 2; n = 9), one suffering only from neuropathy (group 3; n = 9) and one with trophic skin lesions in the contralateral foot (group 4; n = 8), all without macroangiopathy, compared to healthy controls (group 1; n = 9). Femoroarterial injection of small boli (10 mg) of Na-fluorescein allowed repeated investigation of the dye appearance times (AT) and capillary-filling times of forefoot skin capillaries within small periods of time before, during and after reactive hyperemia. At rest, AT was significantly shorter in patients of group 4 (16.8 +/- 4.4 s; p < 0.05) compared with groups 1-3 (34.3 +/- 12.8; 31.7 +/- 11.7 and 35.9 +/- 15.3 s). Fifteen seconds after the end of arterial occlusion, dye propagation to the skin was markedly accelerated in groups 1-3 (19.8 +/- 14.0; 14.4 +/- 7.6 and 18.7 +/- 10.6 s, respectively; p < 0.001), but prolonged in group 4 (18.4 +/- 7.4 s). After 10 min, the values at rest were reestablished. No differences between the four groups were found concerning capillary density and morphology. It is concluded that the development of skin lesions in diabetic patients without significant macroangiopathy may be favored by hyperperfusion and impaired vasoregulation. Intraarterial dye injection presents a valuable tool to assess dynamic alterations of the microcirculation at the level of skin capillaries.

Effect of externally applied skin surface forces on tissue vasculature.

The effect of surface forces on the morphologic pattern of skin capillaries was examined on the anterior surface of the forearm of healthy volunteers. A rig was designed to permit the application of uniaxial forces between two pads attached to the skin surface. A grid was printed onto the skin surface, and mechanical data are presented in terms of force intensity versus strain. During force application the skin capillaries were monitored using vital capillary microscopy. Mean values of force intensity and strain of 1.33N/mm and 10%, respectively, were sufficient to produce virtual obliteration of the blood flow to the capillaries. A simplified finite element model of the tissue was also employed to illustrate the effect of surface forces at different depths within the tissue. This study emphasizes the potentially damaging effects of surface forces on the integrity of the skin vasculature. If these forces are maintained or repeated, cell necrosis and eventual tissue damage would result.

Blood fluidity and endothelial influences on microcirculation

In this survey several methods for studying skin microcirculation are presented. The technical characteristics and the clinical applicability of vital capillary microscopy, laser doppler flowmetry, skin fluorescein angiography and transcutaneous pO2 measurement are described.

The relationship between macro- and microcirculation clinical aspects.

A large number of methods are today available for the clinical evaluation of the arterial blood supply to an extremity or part of an extremity. However, these methods are not sensitive enough for determining the nutritional status of a tissue in the extremity affected by vascular disorders. This is especially true for the skin where most of the blood is used for thermoregulation and only a small fraction goes through the nutritional capillaries. Blood may enter the subpapillary vascular network through AV-shunts and bypass the nutritional skin capillaries. Therefore microcirculatory methods has to be used in order to be able to evaluate the nutritional status of a certain skin area. One of the clinically most useful methods for this purpose is vital capillary microscopy. By classifying structural changes of the nutritional capillaries in an area susceptible to ischemia, the risk of necrosis can be evaluated. Marked discrepancies between the total circulation of the are and the nutritional status of the tissue can be seen especially in patients with peripheral vascular disorders and/or diabetes. The total circulation may be markedly reduced but necrosis does not occur until the nutritional circulation of the ischemic skin area is completely abolished for a certain period of time. On the other hand it is sometimes seen in clinical practise that ischemic skin necrosis may develop in a region with rather good macrocirculation. These findings are of utmost importance when the effect of a certain treatment should be evaluated. The effect has to be studied directly in the target organ, and that is the nutritional vascular bed of the ischemic area.

A simplified evaluation of vital capillary microscopy for predicting skin viability in patients with severe arterial insufficiency.

In the present study the predictive value of a simplified VCM (Vital Capillary Microscopy) classification in assessing the development of skin necrosis was investigated in 69 patients with severe peripheral arterial obliterative disease (AOD) of the leg. The arterial circulation of the foot was evaluated by systolic blood pressure (SBPt). The structure and blood filling of the skin capillaries of all toes and forefeet were evaluated by an ordinary stereo-microscope at a magnification of 10 to 40 times. A three stage classification was used for evaluating the nutritive skin capillaries: Stage A, B and C. The individual patient was classified according to the worst stage found in the foot. The predictive value for the SBPt measurements with regard to the development of skin necrosis was for the best group (21-30 mmHg) 6%, for the middle group (11-20 mmHg) 58% and for the worst group (0-10 mmHg) 56%. The predictive values for the VCM Stages A, B and C were 5, 16 and 93% respectively. The sensitivity with the borderline between Stage A and B + C was 97% and the specificity 53%. With the borderline between stage A + B and C the sensitivity and specificity became 87% and 95% respectively. It may be concluded that the VCM classification with three stages used in the present study seems to be very useful for predicting the risk of skin necrosis in patients with severe AOD.

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.

The Effect of Pulsed Electromagnetic Energy (Diapulse®) on the Survival of Experimental Skin Flaps: A Study on Rats

Experimental skin flaps in rats were treated with an active/non-active Diapulse unit in a double-blind trial to clarify whether or not pulsed electromagnetic energy had any effect on the surviving length of flaps. The observed differences in surviving flap areas between the Diapulse treated group and the untreated group as compared to the predicted survival by fluoresceine and/or vital capillary television microscopy were not statistically significant (p less than 0.10) in a set up, that on a significance level of 5%, would have detected an enhancement of flap survival of greater than or equal to 10% in 98% of trials.

Blood flow cessation at external pressure in rat skinflaps isotope washout compared to vital capillary microscopy

This paper is devoted to elucidate the question: Can cessation of blood flow in a tissue caused by external compression be determined by isotope washout? A depot of a 133Xenon-histamine-solution was injected intradermally into skinflaps in rats and the washout was recorded. The microcirculation in the labeled skin area was studied simultaneously by vital microscopy. External compression was applied and the blood flow cessation external pressure (FCEP) was determined as the minimum external pressure sufficient to arrest the washout of 133Xenon or to stop the movements of red blood cells in the microcirculation visualized. In 12 experiments, the FCEP was on average 46.3 mm Hg as determined by isotope washout and 45.1 mm Hg as determined by vital microscopy. The SD of the difference was 2.7 mm Hg and the range of pressures studied was 18 to 68 mm Hg. The data show that cessation of washout of 133Xenon was an adequate measure of cessation of blood flow in the microcirculation.

Vital Capillary Microscopy

(1973). Vital Capillary Microscopy. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 31, No. sup133, pp. 1-50.