Transitions in skin blood flow fractal scaling: the importance of fluctuation amplitude in microcirculation.

Detrended fluctuation analysis (DFA) of laser Doppler flowmetry (LDF) time series from volar skin reveals three scaling regions: cardiac, cardio-respiratory and local. Scaling exponents, slopes (αC, αCR and αL) of the straight lines, in these regions indicate correlation properties of LDF signal. Transitions from uncorrelated to positive in cardiac (αC) and positive to negative correlations in the cardio-respiratory (αCR) exponent have been observed for vasodilatation signals in response to local heating. However, positive correlation in local region (αL) did not change with vasodilatation. We studied whether the transitions in scaling exponents are correlated with the increase in peak to peak fluctuation amplitude (AF) of LDF signal. LDF signals were normalized to unity using average values of their pulsatile parts: baseline and saturation signals. If AF of normalized LDF signal is ≥0.5, we observed transitions in αC and in αCR but not in αL, in healthy subjects. It is suggested that the transition from positive to negative correlation in αCR with increasing amplitude may be explained by intact arteriolar myogenic activity in healthy young (Y) and middle aged (MA) subjects. In contrast, we did not observe transition in αCR suggesting impaired myogenic activity in patients with essential hypertension (EHT).

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension.

OBJECTIVE: To investigate limb specific differences in cutaneous vascular function in patients (n=33) with essential hypertension (EHT). METHODS: In this observational cross-sectional study, baseline skin blood flow and the response to local heating were measured with a laser Doppler flowmeter (LDF) from the volar region of the forearm and the gaiter area of the foot at supine rest. The fractal analysis, detrended fluctuation analysis (DFA), was used to calculate the correlation properties of skin blood flow, LDF signal. The paired t-test and repeated measures ANOVA were used to determine the response to local heating and compare the scaling exponents of different anatomical locations respectively. RESULTS: We found three linear scaling regions that describe the fractal behavior of LDF signal with their slopes, scaling exponents. For cardiac (α(C)) and cardio-respiratory (α(CR)) scaling exponents, thermal hyperemia (T) induced greater change in the leg (α(C)=1.49 ± 0.26; α(CT)=1.62 ± 0.20 p<0.01 and α(CR)=0.84 ± 0.29 α(CRT)=0.42 ± 0.28 p<0.001) than in forearm (α(C)=1.28 ± 0.13; α(CT)=1.33 ± 0.13 p>0.05 and α(CR)=0.73 ± 0.15; α(CRT)=0.65 ± 0.018 p<0.05). Local scaling exponents (α(L) ≈ α(LT) ~ 1) were not significantly different (p>0.05) and, local lines did not shift in parallel with local heating in both extremities. CONCLUSION: The results of the present study suggest that skin microvascular function is impaired in both extremities in EHT patients. However, myogenic response is not uniform in both extremities and pronounced response to local thermal hyperemia has been observed in the gaiter area compared with the volar region. Further studies are needed to determine if these limb specific microvascular differences is the result of posture-induced structural and functional adaptation.

Fractal scaling of laser Doppler flowmetry time series in patients with essential hypertension.

The full diagnostic potential of the fractal complexity measure, α, of detrended fluctuation analysis (DFA) has not been realized yet. To reveal the impaired mechanisms in the blood flow regulation in patients with essential hypertension (EHT), we studied the laser Doppler flowmetry (LDF) time series by applying DFA. Forearm microvascular blood flow was measured by LDF during supine rest. After a 15 min baseline recording, microvascular response to thermal hyperemia was measured over 30 min. We found three distinct scaling regions; corresponding to the integration of local mechanisms, cardiac effect on local blood flow, and the coupling of extrinsic factors (cardiac and respiratory) to local blood flow by myogenic mechanism. In the control group, local scaling exponent, α(L)=0.96 ± 0.08, did not change but cardiac scaling exponent, α(C)=1.53 ± 0.05, for baseline signal was increased to α(CT)=1.73 ± 0.10 and cardio-respiratory scaling exponent, α(CR)=0.73 ± 0.19, was decreased to α(CRT)=0.24 ± 0.06 during vasodilatation in response to local heating. However, we found significantly different scaling exponents, α(LT)<1, α(CT) ≥ α(C)<1.5 and α(CR) ≈ α(CRT)>0.5 in patients with EHT. Our findings suggest that the local regulatory and the cushioning peripheral vascular functions are impaired in patients with EHT, and vascular/microvascular pathology can be evaluated by applying DFA to LDF signal.

Detrended fluctuation analysis of laser Doppler flowmetry time series.

Detrended fluctuation analysis (DFA) of laser Doppler flow (LDF) time series appears to yield improved prognostic power in microvascular dysfunction, through calculation of the scaling exponent, alpha. In the present study the long lasting strenuous activity-induced change in microvascular function was evaluated by DFA in basketball players compared with sedentary control. Forearm skin blood flow was measured at rest and during local heating. Three scaling exponents, the slopes of the three regression lines, were identified corresponding to cardiac, cardio-respiratory and local factors. Local scaling exponent was always approximately one, alpha=1.01+/-0.15, in the control group and did not change with local heating. However, we found a broken line with two scaling exponents (alpha(1)=1.06+/-0.01 and alpha(2)=0.75+/-0.01) in basketball players. The broken line became a single line having one scaling exponent (alpha(T)=0.94+/-0.01) with local heating. The scaling exponents, alpha(2) and alpha(T), smaller than 1 indicate reduced long-range correlation in blood flow due to a loss of integration in local mechanisms and suggest endothelial dysfunction as the most likely candidate. Evaluation of microvascular function from a baseline LDF signal at rest is the superiority of DFA to other methods, spectral or not, that use the amplitude changes of evoked relative signal.

Evaluation of forearm microvascular blood flow regulation by laser Doppler flowmetry, iontophoresis, and curve analysis: contribution of axon reflex.

The relative contribution of vasodilating factors to the control of blood flow in the forearm cutaneous microcirculation is not well defined. Therefore, a mathematical transformation is introduced to decompose the superimposed signal and to investigate the involved mechanisms separately. Transdermal iontophoresis was used for the delivery of acetylcholine (ACh) or sodium nitroprusside (SNP) into the forearm, and cutaneous perfusion was measured using a laser Doppler flowmeter (LDF). The curve fitting procedure used in this study indicates that the LDF signal in response to ACh iontophoresis can be described by the superposition of two independent hyperbolic response curves. Obviously, each component of LDF signal indicates the existence of a separate mechanism, with corresponding rate constant k, latency T, and the saturation level Fmax. Blockade of C-fiber function (axon reflex) with topical anesthesia removes one of the two components of this response and allows the precise quantification of its contribution. SNP-evoked response also has two components, but their parameters were different from those of ACh. Therefore, ACh and SNP cause vasodilation in the skin microcirculation through different pathways. These findings have implications for clinical studies that use the iontophoresis technique for assessing vascular function and comparing responses to ACh and SNP to evaluate endothelial dysfunction.