Ludwig Caspary

Quantitative Reflection Spectrophotometry: Spatial and Temporal Variation of Hb Oxygenation in Human Skin

Applying a fast scanning reflection spectrophotometer and multicomponent spectra analysis, oxygen saturation (SHb) and relative concentration (CHb) of hemoglobin in the skin were determined at eight skin sites in 11 healthy persons. SHb was significantly higher at the tip of the index finger and big toe (90 +/- 3.9 and 92 +/- 4.2%, respectively) compared with the forehead, volar forearm, back of hand, abdomen, calf and forefoot where mean values varied between 52 and 67% (p < 0.001). CHb also was higher at acral sites (big toe: 2.04 +/- 0.14 arbitrary units (AU); index finger: 2.13 +/- 0.19 AU) than at the other locations (p < 0.0001) where it was between 0.56 +/- 0.12 AU (abdomen) and 0.95 +/- 0.28 AU (forefoot). In the course of time, rhythmical oscillations of both parameters at a frequency of 3-5/min were seen in 68% of the measurements, predominantly at the six proximal sites. Heating the measuring site to 44 degrees C caused a biphasic increase of CHb and SHb which was significant at the proximal sites (p < 0.0001). SHb values came into the range of arterial blood. Temporal and spatial variation of both parameters decreased. Reflection spectrophotometry gives the possibility to directly assess dermal hemoglobin saturation, its physiological variability and reactions to provocation stimuli. Concentration and saturation of hemoglobin in dermal vessels appear definitely different at acral compared with proximal sites.

Skin Surface Oxygen Pressure Fields During Administration of Prostaglandin E1 in Patients with Arterial Occlusive Disease

SummaryProstaglandin E1 is offered as a new therapeutic agent in the treatment of severe peripheral arterial occlusive disease. Especially when treating patients with ulcers or gangrene, the oxygen tension of the skin should improve during PGE1 administration. The new technique of assessing skin surface oxygen pressure histograms allows study of the skin microcirculation in vivo. Oxygen histograms were determined on the forefeet of 19 patients with different degrees of disease and different occlusion levels before and during a single intraarterial infusion of PGE1 at a dosage of 1.5 ng/kg body weight/min. Only 9 patients showed improvement during the infusion period. Skin oxygen pressure was increased to a large extent only in patients assumed to suffer from diabetic microangiopathy. The effect of a long-term therapy with PGE1 on skin microcirculation remains to be settled.

Comparison of Laser-Doppler-Flux and tcPO2 in Healthy Probands and Patients with Arterial Ischemia

Transcutaneous PO2 (tcPO2) and Laser-Doppler-Flux (LDF) were compared on the dorsum of the foot in 20 healthy probands and 35 patients with peripheral arterial occlusive disease at clinical stage II b or IV. The probes were kept at a temperature of 37 degrees C. Using different procedures, we brought about dynamic changes and compared the reaction of the two signals. Venous occlusion resulted in a decrease of both signals to a similar extent in both groups. During leg dependency both signals decreased in the probands suggesting a normal vasoconstrictor response. In most of the patients an increase was observed, but some showed a decrease even at clinical stage IV. LDF had a stronger tendency towards a decrease. On leg elevation, LDF slightly increased in probands and decreased in patients. Here, the tendency towards a decrease was higher for tcPO2. After arterial occlusion reactive hyperemia was more pronounced in probands. Differences between tcPO2 and LDF seem to be mainly due to the different capillary systems contributing to the signal.

Intravenous infusion of iloprost in arterial occlusive disease : dose-dependent effects on skin microcirculation

SummaryTranscutaneous oxygen pressure (tcPo2), laser Doppler flux and capillary microscopy have been used to examine the forefoot skin in 5 healthy men and 8 patients with severe peripheral arterial occlusive disease in order to evaluate the dose dependent effects of iloprost on skin microcirculation. Iloprost was infused IV starting at 0.0625 ng·kg−1·min−1 and doubling the dose every 15 min up to 2 ng·kg−1·min−1.While tcPo2 at an electrode core temperature of 44°C decreased in both patients and controls, there was a significant dose dependent increase in tcPo2 (37°C) in the controls from 0.25 ng·kg−1·min−1. In the patients the reaction was variable: it was decreased in two and increased in 6, with a maximum either at 0.25–0.5 ng·kg−1·min−1 (n=3) or at the highest dose (1.0 or 2.0 ng·kg−1·min−1; n=3). Mean laser Doppler flux in both groups was increased, although the reaction was not consistent in the patients. Density of forefoot skin capillaries was reduced in 3 patients, and in the others the flow velocity was very low. During infusion of iloprost, both an increase in capillary density and blood cell velocity were observed. The effects were of variable intensity and occurred at varying doses, some appeared early and diminished as the dose was increased, and others were found only at 2 ng·kg−1·min−1.Adverse effects were numerous, extending from harmless skin flushing to mental changes and a quickly reversible attack of angina pectoris. It may be possible to divide patients into those with early effects on the microcirculation, at doses of 0.25–0.5 ng·kg−1·min−1, and those in whom the microcirculatory response is preceded and counteracted by the adverse effects.

Orthostatic Vasoconstrictor Response in Patients with Occlusive Arterial Disease Assessed by Laser Doppler Flux and Transcutaneous Oximetry

Posturally induced microvascular constriction normally causes a decrease of transcutaneous oxygen pressure (tCPO2) and laser Doppler flux (LDF) measured on the forefoot at 37°C. The authors used both methods to assess the vasoconstrictor response (VCR) in 31 patients with various degrees of peripheral arterial occlusive disease (PAOD) and analyzed factors that could have influenced the response. Disturbed VCR was indicated by a signal increase following leg dependency, which occurred significantly more often in tCPO2 than in LDF measurements (69% vs 32%, P < 0.001). Correspondingly the median sitting/supine ratio was 2.4 for tcPO 2 and 0.7 for LDF (P < 0.0001). Age and clinical stage had no influence on the VCR. With ankle artery pressures below 50 mmHg an increase of LDF was more probable. TcPO2 predominantly increased with ankle artery pressures up to 100 mmHg, though the sitting/supine ratio of tcPO2 was correlated with ankle artery pressure. In nondiabetics the response of tcPO2 but not of LDF was influenced by the values at rest. Differences between the two methods may be explained in part by their different sample volumes. The authors assume that tcPO2 is predominantly monitoring a local myogenic response while LDF is reflecting venoarteriolar response.

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.

Skin Oxygen Pressure Histograms in Patients with Peripheral Arterial Occlusive Disease During Intraarterial and Intravenous Prostaglandin E1 Infusions of Different Dosages and Their Prognostic Value

Skin surface oxygen pressure fields (tcPO2 [37°C]) reproducibly characterize skin microcirculation in patients with peripheral arterial occlusive disease. These appear suited for investigation of short- and long-term effects of vasoactive drug treatment. The authors studied whether skin surface oxygen pressure histograms change depending on dosage and route of administration of prostaglandin E1 (PGE1), whether they are of predictive value for patients clinical outcome, and whether they normalize after therapy with PGE1 . The authors investigated 15 patients with various degrees of disease and measured forefoot oxygen histograms consisting of at least 80 single tcPO2 (37°C) values before and during intraarterial infusion (1.5, 3, or 6 ng/kg/minute) and intravenous infusion (4.5, or 9 ng/kg/minute). The measurements were repeated two and six hours after the end of intraarterial application of 1.5 ng/kg/minute. Furthermore, the orthostatic vasoconstrictor response was tested. Skin oxygen pressure histograms were controlled after a period of twenty-two (mean) days of intraarterial PGE1 therapy. Resting histograms were left shifted with median tcPO2 (37 ° C) between 1 and 7 mm Hg. During intraarterial application, histograms were shifted to lower tcPO 2 (37 ° C) values in most patients. Only in 3 diabetic subjects with proximal or acral obliterations was a marked increase observed. The alterations were detectable at least two hours after the end of the infusion. During intravenous infusion, histograms did not change in most cases. After long-term therapy, histograms were substantially unchanged. A pathologic vasoconstrictor response, which was present in 10 patients, could not be restored. Despite a marked deterioration of the histograms the clinical outcome was favorable in 7 patients. Patients with a high resting tcPO2 (37 ° C) (median 4 mm Hg and more) and those with a vasoconstriction on orthostasis are likely to respond to PGE1 therapy.

Effects of lloprost on Skin Microcirculation

Prof. Andreas Creutzig, MD, Department of Angiology, Medizinische Hochschule, D-30625 Hannover (Germany) Prostanoids like alprostadil and iloprost are often used in patients with peripheral arterial occlusive disease who are no candidates for surgery or angioplasty. Melillo et al. A[l] stated that evidence about the effect of intravenous prostanoids on cutaneous P(7⁄8 in critical limb ischemia is scarce and somewhat inconsistent. Unfortunately, their report on tcP < 3⁄4 and tcPC(3⁄4 during treatment of critical limb ischemia with iloprost does not elucidate this problem. They found that tcPC1⁄2 in the supine position erratically changed during the treatment period with an increase in only three out of eight limbs. The main disadvantage of this study is that the authors did not use the same dose of iloprost for all patients. Their drug infusion rate varied between 1.0 and 2.0 ng/kg body weight/min. They adopted the manufacturer’s instruction to titrate individually to the maximal tolerated dose. There are not only interindividual differences of microcirculatory responses to iloprost but also a marked dose dependency. It is some years ago that we reported on effects of different doses of iloprost on skin micro-circulation of healthy volunteers and patients with peripheral occlusive disease of different degrees [2]. We found quite variable reactions in the patient group, too. tcP < 3⁄4 (37 °C) decreased in two, but increased in 6 patients, with a maximum either at 0.25-0.5 ng/kg/min (n = 3) or at the highest dose (1.0 or 2.0 ng/kg/min, n = 3). Mean laser Doppler flux was increased, although the reaction was not consistent. We observed an increase of both capillary density and blood cell velocity. In some patients effects of the infusion were pronounced and were visible at low doses, but in others effects did not appear or were found only at the highest dose, when adverse reactions were already present. Effects of iloprost on skin microcirculation in patients with peripheral arterial occlusive disease are variable to a large extent. Unfortunately, so far predictive parameters are not known. However, from our study as well as from the clinical point of view we feel that the titration of iloprost dosage according to the side effects is not the best way. The question of whether positive effects on the cutaneous microcirculation are predictors of the clinical efficacy is still unsolved. If microcirculatory responders were also clinical responders the adequate dose might be lower (0.25-0.5 ng/kg/min) than those actually employed. This would be desired because side effects are dose-dependent and occur in more than 70% of patients treated with the titrated dose [3]. Actually a recently presented study did not reveal any differences in clinical outcome between low dose and high dose iloprost therapy and the authors concluded that the optimal dose would be < 1.0 ng/kg/min [4].