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Unlabelled: The relative magnitude of endothelial versus non-endothelial vasodilatation in the skin of limbs of patients with peripheral arterial occlusive disease (PAOD) is not known. We therefore investigated the effects of iontophoretically administered sodium nitroprusside (SNP) and acetylcholine (Ach) on the skin microvascular blood flow measured by laser-Doppler fluxmetry., Methods: Blood flow changes in the skin was measured on the dorsal side of the foot in three different groups: (i). 11 patients (mean age 73 years) with PAOD, with a mean ankle-brachial index of 0.46, (ii). eight age-matched elderly healthy volunteers (mean age 73 years) and (iii). young healthy group (n=15; mean age 34 years). For drug administration with iontophoretic technique we used a Periont Micropharmacology System., Results: In patients with PAOD, Ach produced a vasodilatation, which was directly correlated to the strength of iontophoretic stimulation. The difference between the patients and the elderly healthy group was significant after the highest stimulation (160 s, P<0.05). The same pattern was found during stimulation with SNP. In comparison with the young healthy group there was a statistically significant difference (P<0.001) with a slower and less pronounced response in patients with PAOD., Conclusion: In patients with PAOD it is possible to achieve local vasodilatation from a baseline level by delivering Ach or SNP through the skin. The two vasodilators, acting by different mechanisms, produced the same vasodilatation response, suggesting that the impaired vasodilatation capacity in patients with peripheral arterial disease may not emanate primarily from local endothelial dysfunction in the skin microcirculation.

A decrease in capillary flow due to hyperleucocytosis may cause impairment of organ perfusion in patients with leukaemia. In order to evaluate the effects of different cell types of leukaemic cell origin on skin capillary circulation we have studied patients with (a) chronic lymphocytic leukaemia (CLL) (n = 6) and (b) acute non-lymphocytic leukaemia (ANLL) (n = 6) or chronic granulocytic leukaemia (CGL) (n = 5). Capillary blood cell velocity (CBV) in fingernail-fold capillaries was measured by videophotometric capillaroscopy. After a 1-min arterial occlusion at the finger base, the post-occlusive reactive hyperaemia was evaluated by measuring the peak (p) CBV and the time to pCBV. In patients with ANLL/GGL, both resting CBV and pCBV were lower than in healthy control subjects. In the CLL patients these values were not significantly different compared to controls. In a few patients the time to pCBV was markedly prolonged. Symptoms attributable to hyperviscosity were more common in patients with ANLL/CGL and low CBV values. It is suggested that the cell size of leucocytes may be an important factor in the development of hyperviscosity syndromes and organ malperfusion in leukaemic patients.

Using videophotometric capillaroscopy and laser Doppler fluxmetry, we have investigated skin microvascular reactivity in the fingers of 14 diabetic patients with severe, late complications 20 months after combined kidney and pancreas transplantation. The results were compared with those obtained in 20 diabetic patients awaiting pancreas transplantation and in 19 healthy subjects. The capillary blood cell velocity at rest (P less than 0.01) and during postocclusive reactive hyperemia (P less than 0.05) was significantly lower in both patient groups than in the healthy controls. However, the time to peak capillary blood cell velocity during hyperemia was normal in the post-transplantation group (NS) but significantly prolonged in the pretransplantation group (P less than 0.01). The ability to decrease flow during venous stasis-the so called venoarte-riolar reflex--was strongly impaired in the pretransplantation group (P less than 0.001) but less so in the post-transplantation group (P less than 0.05) as compared to healthy controls. It may be concluded that diabetic patients, after combined kidney and pancreas transplantation, show a tendency towards better microvascular reactivity than those awaiting transplantation.

Disturbances of vasomotor activity and veno-arteriolar reflex mechanism probably promote cutaneous edema formation. Videophotometric capillaroscopy was used to measure nailfold skin capillary blood cell velocity (CBV) and its response to increased transmural pressure induced by venous occlusion in healthy subjects, normal pregnancies and patients with preeclampsia. Vasomotion, assessed by rhythmic variation of CBV, was also recorded. Both frequency (3-10 cycles/minute) and amplitude (0.01-0.23 mm/s) of CBV fluctuations were similar in all groups investigated. In healthy controls basal CBV was positively correlated with the amplitude of individual velocity fluctuations (r = 0.89). CBV response to venous occlusion was significantly reduced (p less than 0.05) in preeclampsia compared to normal pregnancies and non-pregnant controls. This finding indicates impaired veno-arteriolar reflex which may contribute to the edema formation seen in preeclampsia. It is suggested that vasomotor activity may serve as a physiological modulator of vascular resistance and hence CBV.

By videophotometric capillaroscopy, blood flow dynamics in the nutritional skin capillaries of man can be quantified. In this double-blind crossover study the acute effect of nifedipine on finger nailfold capillary blood cell velocity (CBV) was investigated in 10 healthy subjects. At the moment of administration of 10 mg nifedipine or placebo sublingually, a transitory but significant increase in heart rate and reduction of digital pulse amplitude (DAPA) were seen. Subsequent measurements of DAPA and heart rate were not significantly different from the baseline ones. CBV however increased after 10 min to a maximum of 49% above baseline values (P less than 0.05) after nifedipine but was unaffected by placebo. The reactive hyperaemia response in the capillaries were unaffected by both placebo and nifedipine. The decrease in DAPA and increase in heart rate upon administration of the drug or placebo are compatible with an increase in sympathetic activity. The subsequent increase in CBV indicates that nifedipine diminishes precapillary vascular tone. However, the drug seems to affect arterio-venous shunt flow to a lesser extent since DAPA did not increase significantly. Videophotometric capillaroscopy is a suitable method for studying the effects of pharmacological compounds on nutritional circulation in human skin.

Nailfold skin capillary blood cell velocity (CBV) was studied at rest and during post-occlusive reactive hyperaemia after a 1 min arterial occlusion (PRH1) in: (i) both hands of patients with arterial obliterative disease (AOD) of one arm, (ii) patients with polycythaemia, before and after a moderate haemodilution and (iii) healthy controls. CBV was analysed by videophotometric cross-correlation utilizing the different optical densities produced by the passage of erythrocytes, leucocytes and plasma gaps through the monitored capillary. Resting CBV in the patients with unilateral AOD was similar in equivalent fingers of both hands. However, the time to peak (p)CBV during PRH was significantly prolonged in the low-pressure arm as compared to the contralateral arm. pCBV was also delayed in the patients with polycythaemia as compared to the healthy controls. This delay was not affected by the replacement of 500-750 ml of blood with the same amount of a 6% Dextran 70 solution. The mean capillary blood cell velocity during rest (rCBV) did not differ between controls and patients before or after the haemodilution. The prolonged time to pCBV in the polycythaemic patients may be attributed to increased blood viscosity that is presumably not significantly influenced by a moderate haemodilution using Dextran 70. The marked delay to pCBV observed distal to the arterial obstruction in patients with AOD probably is an effect of the lower arterial pressure, presumably involving an alteration of vascular smooth muscle function.

Measurement of transcutaneous oxygen tension (pTcO2) has become a rather widely used technique. The relation of pTcO2 to skin microcirculatory parameters is, however, unclear. Capillary blood cell velocity (CBV) was compared with transcutaneous oxygen tension (pTcO2) of the finger in seven volunteers on change of hydrostatic pressure and contralateral cooling. On increase in hydrostatic pressure and also with contralateral cooling CBV decreased, while pTcO2 remained unchanged. This finding can be explained by a heat-induced local vasodilation under the pTcO2 probe in spite of a general increase in vasomotor tone. During decreasing perfusion pressure CBV was unchanged, while pTcO2 fell. This shows that with reduction in driving pressure skin pO2 is lowered. Teh absence of a decrease in CBV under these circumstances may be explained by a closure of the arteriovenous shunts, with diversion of blood into the superficial nutritional capillaries. It is suggested that CBV is related to changes in skin vasomotor tone. The pTcO2 findings indicate that the skin vasculature under the isothermally heated (44 degrees C) sensor is dilated and does not respond to vasoconstrictor stimuli.

Finger-skin microcirculation and its reactions to sympathetic stimuli were investigated in 12 patients with sympathetic dystrophies, secondary to trauma or other diseases. Nailfold-skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy. Laser Doppler fluxmetry was used to provide an index of skin circulation in vessels in addition to the superficial capillaries. Both CBV and laser Doppler flux (LDF) values were significantly lower in the patients, compared with the healthy controls (P less than 0.05), despite the fact that skin temperature was the same in both groups. During cooling of the contralateral hand, CBV and LDF decreased markedly (22-60%) in the control group but not in the patients (0-13%). The decrease in skin perfusion normally seen upon lowering of the hand was also impaired in the patient group (7%) compared with controls (42%) (P less than 0.05). These impaired vasomotor reflex responses are consistent with sympathetic dysfunction and may well explain some of the typical features of the syndrome, e.g. limb oedema.

In a recent study we found skin capillary blood cell velocity (CBV) at rest, laser Doppler flux (LDF), and its response to lowering of the hand to be reduced in the dystrophic hand of patients suffering from sympathetic dystrophies. This study confirms these previous findings. Four of the 12 patients investigated felt intermittent pain in the "healthy" hand. Basal CBV, LDF, and reaction during dependency were not impaired in the asymptomatic hand compared with controls. However, during cooling of the contralateral hand CBV and LDF decreased significantly (median 44 and 37.5%) in the control group but neither in the affected nor in the asymptomatic hand among patients. Sympathetic blockade significantly increased both CBV and LDF in the dystrophic hand (median 58 and 20%), but no obvious beneficial symptomatic effect was noted. The lack of response to contralateral cooling in both hands indicates a disturbance of a central nervous mechanism in patients with unilateral sympathetic dystrophies.

The effects of insulin infusion (1.5 u/h and 15 u/h) on finger nailfold capillary diameter, microcirculatory resting flow and microvascular reactivity were studied in eleven Type 1 diabetics. Blood glucose was maintained at pre-infusion values by intravenous glucose infusion as necessary. Venous limb capillary diameter was significantly wider on 15 u/h compared with pre-infusion values (14.3 +/- 4.5 micron pre, 16.9 +/- 5.1 micron 15 u/h, p less than 0.01. Resting blood flow measured by laser doppler flowmetry increased on the low dose infusion compared with pre-infusion values (2.6 +/- 1.7 V pre, 3.3 +/- 1.9 V 1.5 mu/h, p less than 0.05) but fell on high dose infusion (2.5 +/- 1.9 V, p less than 0.02). Dynamic measurement of capillary blood flow velocity in single capillaries suggested that insulin infusion increased the circulatory debt repayment following 60 s arterial occlusion. The high dose infusion caused a significant impairment of the reflex rise in precapillary resistance that normally accompanies venous congestion. It is concluded that insulin has effects on skin microvascular haemodynamics that are independent of the hormone's hypoglycaemic action.

The integrity of the regulation of skin microvascular blood flow has been studied in Type 1 diabetic patients with and without clinical evidence of microvascular complications after a long duration of diabetes. 13 uncomplicated patients with a mean duration of diabetes of 38 +/- 6 (SD) yr were compared with 10 patients with proliferative retinopathy and a group of healthy control subjects. Using laser Doppler flowmetry 2 distinct microvascular responses were examined in the skin of the finger: (a) reactive hyperaemia following the release of one minute's digital arterial occlusion, a response that is independent of neural mechanisms, and (b) the fall in skin blood flow on venous occlusion that occurs due to the veno-arteriolar reflex, a response that depends upon intact local sympathetic nervous function. The duration of reactive hyperaemia was longer in the complicated patients than either the group without complications (69 +/- 38: 23 +/- 17 s, p less than 0.01) or the healthy controls (27 +/- 20 s, p less than 0.05). In contrast the percentage fall in laser Doppler blood flow on venous occlusion was significantly less (p less than 0.01) in both diabetic groups than that achieved in healthy controls, (50 +/- 14% controls; 26 +/- 12% uncomplicated group; 28 +/- 12% patients with retinopathy). There was no difference in current or recent diabetic control in the 2 diabetic groups. These results suggest that some degree of sympathetic neuropathy is almost inevitable after a long duration of Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously reported a lack of correlation between the reactions of finger skin capillary blood cell velocity (CBV) and transcutaneous oxygen tension (pTcO2) to different hydrostatic pressures. In the present study the influence of different venous and arterial pressures on nailfold CBV and pTcO2 of the dorsum of the middle phalanx was investigated. In six subjects venous occlusion (50 mm Hg) was performed with the hand at heart level and 40 cm above heart level. At heart level venous occlusion caused a marked reduction in CBV from 0.59 to 0.02 mm/s (p less than 0.01) while pTcO2 was not significantly affected. When the hand was raised 40 cm above heart level CBV remained unchanged but pTcO2 fell from 58.8 to 41.8 mm Hg (p less than 0.001). Venous occlusion in this position caused a decrease in CBV and a further decrease in pTcO2. In another 5 subjects arterial occlusions of varying duration (0.5, 1, 2, 6, 15 min) were performed at the finger base. As judged by the CBV, reactive hyperemia (RH) was always present when duration of occlusion was one minute or more. Post-occlusive pTcO2 was significantly increased compared to baseline pTcO2 (p less than 0.05) only after the 15 min occlusion. Thus, there is a marked difference in the responses of CBV and pTcO2 to variations in venous and arterial pressures. The lack of response of pTcO2 to manoeuvers that result in autoregulatory adjustment of CBV probably reflects the local heating of the probe which causes maximal vasodilation in the underlying skin.

Synchronous assessments of microcirculatory flow in human skin have been made by the techniques of laser Doppler flowmetry and dynamic capillaroscopy in adjacent areas of the same nailfold. Microvascular flow was studied at rest, following release of arterial occlusion and during application of venous occlusion in seven normal subjects. Despite broad comparability in the pattern of responses recorded by the two techniques certain significant differences were observed. Vasomotor activity of a similar frequency (4 to 9 cycles per min) was recorded by both techniques, but the activity was asynchronous. The amplitude of the cyclical change in the mean resting flow value recorded by dynamic capillaroscopy was considerably greater than that recorded by laser Doppler (X +/- SD, 25.3 +/- 7.0% mean rest flow; 11.4 +/- 4.9% mean rest flow, p less than 0.01). The time to peak flow following release of a 60 s arterial occlusion was significantly longer as assessed by dynamic capillaroscopy (5.7 +/- 1.6 s: 3.3 +/- 1.0 s. p less than 0.02). In response to a venous congestion pressure of 50 mm Hg, capillary flow rate fell to 24 +/- 6% of the resting flow value as assessed by dynamic capillaroscopy over the first 30 s of occlusion. Laser Doppler flowmetry also recorded a fall in microcirculatory flow to 59 +/- 21% of resting flow value during this period, but this reduction was significantly less than that recorded by dynamic capillaroscopy (p less than 0.05). These discrepancies are interpreted as evidence that laser Doppler flowmetry records blood flow in vessels in addition to the superficial, nutritional capillaries.

We have studied skin microvascular autoregulatory responses in healthy control subjects (n = 11) and three subgroups of uncomplicated Type 1 diabetics. Group 1 (n = 10) had a duration of diabetes of less than one year. Group 2 (n = 10) had a mean duration of diabetes of 11 years. Group 3 (n = 9), of similar duration to group 2, were selected on the basis of having HbAl values persistently below 9%. To assess autoregulatory capacity we determined time to peak capillary flow velocity (CBV) in single nailfold capillaries following release of 60 s arterial occlusion by videophotometric capillaroscopy, and the percentage fall in finger skin rest flow measured by laser Doppler flowmetry when 50 mm Hg venous occlusion was applied. Time to peak CBV was prolonged in groups 1 and 2 compared to controls, (controls 7.7 +/- 1.4 s, mean +/- ISD, group 1 10.7 +/- 2.9 s, p less than 0.01; group 2 11.6 +/- 3.0 s, p less than 0.002) but not in group 3 (9.3 +/- 3.0 s, NS). The percentage fall in resting microcirculatory flow in response to venous occlusion was reduced in groups 1 and 2 compared to controls (controls 57 +/- 16%, group 1 40 +/- 19%, p less than 0.05; group 2 22 +/- 16%, p less than 0.002). In group 3 the response was significantly different from the control value (group 33.7 +/- 20%, controls 57 +/- 16%, p less than 0.05). Thus skin microvascular autoregulatory responses are disturbed within the first year of diabetic life and after 10 years disease duration the impairment is more marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurements of human skin capillary blood cell velocity (CBV) were performed by videophotometric capillaroscopy using a crosscorrelation technique. Mean resting (r) CBV in a group of 64 healthy subjects (age 20-82; 33 men) was 0.60 +/- 0.51 (SD) mm/s at a skin temperature of 30.9 +/- 3.2 degrees C. Skin temperature, but not rCBV, was significantly higher in the men. rCBV showed a weak positive correlation with skin temperature with a marked increase of high rCBV values when skin temperature was more than 31 degrees C. During the postocclusive reactive hyperemia (PRH) after a one-minute arterial occlusion, CBV reached a maximal velocity of 1.17 +/- 0.66 mm/s at 7.8 +/- 2.4 s after cuff release. This PRH response was reproducible with regard to peak velocity (pCBV) and the time to pCBV. The percentage increase of CBV during PRH was inversely correlated to skin temperature (r = -0.69). The results of the present study are proposed as a basis for further studies of human skin capillary circulation in health and disease.

Laser Doppler fluxmetry (LDf) is a noninvasive technique measuring blood cell flux, e.g. in human skin. By a new integrated probe the measuring volume has been increased sevenfold. Using this probe we have investigated dynamic reactions in the skin microcirculation of the big toe in nine patients with various degrees of obliterative arteriosclerosis and in ten healthy control subjects. When position was changed from the supine to the sitting a significant decrease in skin perfusion was seen in healthy subjects but not in the patients. The time to peak flow during reactive hyperemia after a three minute arterial occlusion was significantly (p less than 0.01) longer in the patients (117 +/- 81 s) than in the controls (24 +/- 6 s). We conclude that LDf, using this multiprobe, is of value for diagnosing patients with obliterative arteriosclerosis, as well as for studying dynamic reactions in the human skin microcirculation in health and disease.

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.

Blood viscosity and peripheral vascular resistance have been reported to be increased in preeclampsia, indicating the possibility of an impaired capillary circulation. Nailfold skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in 14 healthy pregnant women and 12 preeclamptic patients. No significant difference was found between basal CBV in the preeclamptic group (median 0.58 mm/s) and the healthy controls (0.52 mm/s). Following infusion of dextran 70 in preeclamptic patients CBV at rest increased to 154% of pre-infusion values (p less than 0.05). The time to peak CBV during post-occlusive reactive hyperemia was almost equal in the two groups and did not change in the preeclamptic group after dextran 70 administration. The enhanced dermal microcirculation following infusion of dextran 70 may be explained by hemodynamic and hemorheological effects, which presumably would be of greater importance if also present in the placental nutritive circulation.