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Transcutaneous oximetry (TcpO2) performed at 37 and 44 degrees on the dorsum of the foot and capillary microscopy of the nailfold of the big toe were applied to 85 patients with various (including asymptomatic) stages of lower limb ischemia to appreciate the relationship between (disturbances in) capillary perfusion and skin oxygen tension. In mildly diseased patients, capillary perfusion as measured by direct observation, was preserved. In critically ischemic patients in the supine position, red blood cell-perfused capillary density was reduced. Nutritive perfusion was severely reduced and showed an absent reactive hyperemia after a 1-min arterial occlusion. Also, postural vasoconstrictive activity was reduced. TcpO2 measured at 37 degrees was very low already in mildly diseased patients, illustrating the poor oxygen diffusion toward the skin. At 44 degrees, TcpO2 was severely reduced in critically ischemic patients. Reactive hyperemic response and postural vasoconstriction were suppressed, due to local heating of the skin. Measurement of the TcpO2 has limitations in the assessment of nutritive perfusion, as opposed to capillary microscopy, since it is an indirect measure of skin perfusion, not necessarily derived from capillaries only. The obligatory local skin heating impairs physiological studies as to hyperemic reserve capacity or postural constriction mechanisms. Thus, transcutaneous oximetry is a poor method of characterizing pathophysiological mechanisms occurring in skin nutritive microcirculation. However, capillary microscopy and transcutaneous oximetry can give additive information as to the severity of peripheral ischemia. Peak red blood cell velocity during reactive hyperemia using capillary microscopy and the resting TcpO2 at 44 degrees, both measured in the supine position, appeared to be valuable microcirculatory parameters in detecting critical limb ischemia.

TMo date, capillary microscopy, transcutaneous oximetry (tcpO2) and laser Doppler fluxmetry are frequently used in the investigation of skin microcirculation in patients with lower limb ischaemia. The concomitant microcirculatory disturbances may be useful in addition to macrocirculatory parameters to discriminate the different degrees of ischaemic severity. The best ways of application of these methods and the choice of the best parameters to assess ischaemia have been insufficiently investigated. Therefore, skin microcirculation was investigated with the use of these techniques in 130 patients with different stages of lower limb ischaemia, divided according to their ankle-to-brachial pressure index (ABI). Patients were investigated in the sitting and the supine position. Measurements were performed at rest and during reactive hyperaemia following arterial occlusion, and before and after local skin heating. The reactive hyperaemic response using laser Doppler fluxmetry differed in every patient group investigated. Capillary red blood cell velocity was markedly impaired in critically ischaemic patients (ABI < 25%). Transcutaneous oxygen pressure measurements at rest rendered the highest positive predictive value (PV; 87%) to classify patients as having clinically severe ischaemia (Fontaine 3 or 4). Ankle and toe pressure measurements provided a PV value of 78%. Microcirculatory parameters and techniques appear to be useful as an addition to standard macrocirculatory techniques to assess the severity of lower limb ischaemia. This is particularly of importance in patients in whom macrocirculatory parameters are unattainable.

Continuous wave Doppler velocimetry was performed in brachial, femoral and cerebral arteries in four preterm, four small-for-gestational-age (SGA) and eight appropriate-for-gestational age (AGA) polycythaemic newborns before and at 3 and 24 h after partial plasma exchange transfusion and in 18 matched controls at 3 and 24 h after birth. In peripheral arteries, end-diastolic flow velocity was zero in all eight AGA controls, but only in two of the other infants. Consequently, mean flow velocity and red cell transport in AGA controls were significantly lower than in the other five groups, which did not differ. Partial plasma exchange transfusion did not influence flow velocities and red cell transport in peripheral arteries, but normalized the flow velocities in cerebral arteries in all three subgroups of polycythaemic infants, which were lower than in control infants. Cerebral red cell transport in controls increased significantly between 3 and 24 h, and in polycythaemic infants between 0 and 3 h after partial plasma exchange transfusion. In conclusion, reduction in haematocrit had different effects on blood flow velocity and red cell transport of peripheral and cerebral vessels, suggesting that the increased cerebral blood flow velocity after partial plasma exchange transfusion is not simply due to a reduction in viscosity or oxygen content of the blood. The lower peripheral blood flow velocities in normocythaemic AGA infants as compared to all other groups, suggest that the level of maturity is an important determinant for the capacity to regulate blood flow.

Posturally induced microvascular constriction in the skin of the leg is disturbed in severe ischaemia. It is unknown whether this disturbance is of local or central origin and whether the stage of ischaemia at which this disturbance occurs differs when the nutritive and thermoregulatory flow levels are compared. We investigated the effect of posture on the skin microcirculation in 21 patients with unilateral severe ischaemia. The results were compared with those from the contralateral, asymptomatic leg and with results from 11 age-matched controls. Patients were investigated in supine and sitting positions, using capillary microscopy to measure nutritive flow, and laser Doppler fluxmetry (LDF) to measure thermoregulatory flow, of the big toes. In the supine position, capillary flow and LDF were lower in the diseased than in the asymptomatic and control legs. After changing from the supine to the sitting position, capillary perfusion decreased in all three groups, but was most pronounced in the controls. Laser Doppler flux decreased in the controls, but increased in the diseased legs, suggesting disturbed vasoconstriction mechanisms in the deeper skin microvessels. These findings indicate that in severe limb ischaemia, posturally induced microvascular reactivity is sustained at the nutritive level but not at the thermoregulatory level. This disturbed reactivity is considered a local phenomenon, as it is not observed in the contralateral leg.

Background: Patients suffering from severe lower limb ischemia may experience pain relief on leg dependency despite the fact that dependency normally results in arteriolar vasoconstriction. To clarify this possible paradox, skin microcirculation of the limb was investigated in 75 patients with different stages of lower limb ischemia and in 12 asymptomatic subjects., Methods and Results: Using nailfold capillary video microscopy, red blood cell-perfused capillary density and diameter and red blood cell velocity were assessed in supine and sitting positions. Capillary density increased by changing from the supine to the sitting position, especially in patients with limb-threatening ischemia (showing a 4.5-fold increase versus a 1.5-fold increase in asymptomatic subjects). In subjects without or with mild ischemia, capillary perfusion was two to four times lower in the sitting than in the supine position. In patients with limb-threatening ischemia, perfusion was strongly reduced, being slightly higher in the sitting position. Patients with relief of pain while sitting did not always have a higher capillary perfusion but did have a higher capillary density in the sitting position., Conclusions: The arteriolar postural vasoconstrictive mechanism at the nutritive level is still intact in subjects without or with mild ischemia but not in patients with severe ischemia. Capillary recruitment rather than disturbed arteriolar vasoconstriction could explain why patients with severe leg ischemia prefer leg dependency.

1. Skin microcirculation was investigated in 12 asymptomatic subjects and 76 patients, grouped according to their ankle-to-brachial systolic blood pressure index, in order to evaluate to what extent posturally induced microvascular constriction is dependent on the stage of leg ischaemia at different local skin temperatures. 2. Skin microcirculation was assessed in the supine and sitting position by using laser Doppler fluxmetry at unheated skin temperature and at 36 degrees C, and transcutaneous oximetry at 37 degrees C and 44 degrees C. 3. Skin perfusion and oxygenation diminished with decreasing ankle-to-brachial systolic blood pressure index. In healthy control subjects, perfusion and oxygenation were reduced when changing from the supine to the sitting position, but were enhanced in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure less than 30%), indicating disturbed posturally induced vasoconstriction. 4. Increasing the local skin temperature resulted in a higher perfusion and masked the posturally induced vasoconstriction in healthy subjects. In patients with severe leg ischaemia, however, perfusion was unaltered by the temperature increase, apparently because the microvessels were already maximally dilated. The induction of reactive hyperaemia produced no additional increase in perfusion or oxygenation. 5. It is concluded that posturally induced microvascular constriction in the skin is disturbed in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure index less than 30%). Disturbed microvascular constriction upon dependency was also seen in healthy subjects after local skin heating. This suggests that posturally induced vasoconstriction is mainly regulated by local mechanisms.

To determine whether postoperative oedema could be predicted preoperatively by microcirculatory parameters, we studied nutritive capillary blood flow in 21 patients before and after limb salvage procedures. All patients had severe lower limb ischaemia and underwent femoro-popliteal or femoro-crural bypass surgery. The systolic ankle-branchial arm index and systolic toe pressure were used as macrocirculatory parameters. Intravital capillary microscopy was used to measure red blood cell (RBC) and peak RBC velocity and time to peak RBC velocity after release of a 1 min arterial occlusion in the nailfold of the toe. Transcutaneous pO2 was measured on the dorsum of the foot at rest, during oxygen inhalation and following a release of a 5 min occlusion. After surgery the mean systolic ankle-brachial index and systolic toe pressure and all transcutaneous pO2 parameters improved significantly (P less than 0.001). Mean peak RBC velocity increased from 0.156 mm/s to 0.310 mm/s (P less than 0.05), indicating that the reactive hyperaemic response in the capillary bed had improved. Eleven patients developed postoperative oedema. There were no differences in postoperative macro and microcirculatory parameters between the patients with oedema (n = 11) and those without oedema (n = 10). However, preoperatively RBC velocity and peak RBC velocity were significantly lower (P less than 0.05) and time to peak RBC velocity was significantly longer (P less than 0.01) in patients who developed oedema. These findings show that in patients with severe limb ischaemia vascular surgery improves both macro- and microcirculatory blood flow, but that these patients develop oedema after vascular surgery when microcirculatory blood flow is compromised preoperatively.

Epidural spinal cord electrical stimulation (ESES) was performed on 10 patients with severe limb ischemia due to atherosclerotic disease. Microcirculatory parameters were assessed before and after ESES. Bright field microscopy was used to assess capillary diameters and red blood cell (RBC) velocity in the dorsum of the foot. Fluorescein microscopy was used with intravenously injected sodium fluorescein to study capillary density and sodium fluorescein appearance time in the dorsum of the toe. The systolic ankle/arm pressure ratio and toe pressure measurements were used as macrocirculatory parameters. After ESES, clinical improvement was confirmed by intravital microscopy. Capillary density increased (p less than 0.001), RBC velocity in capillaries already perfused before ESES increased from 0.054 mm/sec to 0.762 mm/sec (p less than 0.001), and sodium fluorescein appearance time decreased from 72 to 45 seconds (p less than 0.001). Capillary diameter did not change significantly so that the increase in RBC velocity may be interpreted as enhanced volume flow. Systolic ankle/arm pressure ratios and digital arterial pressure did not change significantly. The current results show that in patients with severe occlusive arterial disease of the lower limbs, ESES recruits capillaries not perfused in the control situation and enhances skin blood flow, improvements that may explain the beneficial clinical effects of ESES.