Abnormal blood flow in the sublingual microcirculation at high altitude

We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas. Microcirculatory flow index (MFI) was calculated from the moving images of microcirculatory red blood cell flow, and comparison was made between the baseline and high altitude measurements. Peripheral oxygen saturation (SpO2) and Lake Louise scores (LLS) were recorded along with MFI. Our data demonstrate that there was a significant reduction in MFI from baseline to 4,900 m in small (less than 25 μm) and medium (26–50 μm) sized blood vessels (P = 0.025 and P = 0.046, respectively). There was no significant correlation between MFI and SpO2 or MFI and LLS. Disruption of blood flow within microcirculatory may explain persistent abnormal oxygen flux to tissues following the normalisation of systemic oxygen delivery that accompanies acclimatisation to high altitude

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

Can transcutaneous oximetry detect nutritive perfusion disturbances in patients with lower limb ischemia?

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 ischemi

Cell Communication in the Basal Cells of the Human Epidermis

Electrotonic spread can be measured in the basal cells of the human epidermis. The communication between neighboring cells is high, whereas no leak to the intercellular spaces could be detected. The specific resistance of the membranes between the cells is about 10 Ωcm(2). This finding suggests that for those particles that are able to pass the cell membrane the intracellular path through the epidermis is at least as suitable as the path through the intercellular spaces

Posturally induced microvascular constriction in patients with different stages of leg ischaemia: effect of local skin heating

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 mechanism

Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia

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 le