Studying Erythromelalgia Using Doppler Flowmetry Perfusion Signals and Wavelet Analysis-An Exploratory Study.

Erythromelalgia (EM) is a rare disease, which is still poorly characterized. In the present paper, we compared the hand perfusion of one female EM patient, under challenges, with a healthy control group. Using a laser Doppler flowmeter (LDF) with an integrated thermal probe, measurements were taken in both hands at rest (Phase I) and after two separate challenges-post-occlusive hyperemia (PORH) in one arm (A) and reduction of skin temperature (cooling) with ice in one hand (B) (Phase II). The final measurement periods corresponded to recovery (Phases III and IV). The control group involved ten healthy women (27.3 ± 7.9 years old). A second set of measurements was taken in the EM patient one month after beginning a new therapeutic approach with beta-blockers (6.25 mg carvedilol twice daily). Z-scores of the patient's LDF and temperature fluctuations compared to the control group were assessed using the Wavelet transform (WT) analysis. Here, fluctuations with |Z| > 1.96 were considered significantly different from healthy values, whereas positive or negative Z values indicated higher or lower deviations from the control mean values. Cooling elicited more measurable changes in LDF and temperature fluctuations, especially in higher frequency components (cardiac, respiratory, and myogenic), whereas PORH notably evoked changes in lower frequency components (myogenic, autonomic, and endothelial). No significant Z-score deviations were observed in the second measurement, which might signify a stabilization of the patient's distal perfusion following the new therapeutic approach. This analysis involving one EM patient, while clearly exploratory, has shown significant deviations in WT-derived physiological components' values in comparison with the healthy group, confirming the interest in using cold temperature as a challenger. The apparent agreement achieved with the clinical evaluation opens the possibility of expanding this approach to other patients and pathologies in vascular medicine.

The acute adaptation of skin microcirculatory perfusion in vivo does not involve a local response but rather a centrally mediated adaptive reflex.

Introduction: Cardiovascular homeostasis involves the interaction of multiple players to ensure a permanent adaptation to each organ's needs. Our previous research suggested that changes in skin microcirculation-even if slight and distal-always evoke an immediate global rather than "local" response affecting hemodynamic homeostasis. These observations question our understanding of known reflexes used to explore vascular physiology, such as reactive hyperemia and the venoarteriolar reflex (VAR). Thus, our study was designed to further explore these responses in older healthy adults of both sexes and to potentially provide objective evidence of a centrally mediated mechanism governing each of these adaptive processes. Methods: Participants (n = 22, 52.5 ± 6.2 years old) of both sexes were previously selected. Perfusion was recorded in both feet by laser Doppler flowmetry (LDF) and photoplethysmography (PPG). Two different maneuvers with opposite impacts on perfusion were applied as challengers to single limb reactive hyperemia evoked by massage and a single leg pending to generate a VAR. Measurements were taken at baseline (Phase I), during challenge (Phase II), and recovery (Phase III). A 95% confidence level was adopted. As proof of concept, six additional young healthy women were selected to provide video imaging by using optoacoustic tomography (OAT) of suprasystolic post-occlusive reactive hyperemia (PORH) in the upper limb. Results: Modified perfusion was detected by LDF and PPG in both limbs with both hyperemia and VAR, with clear systemic hemodynamic changes in all participants. Comparison with data obtained under the same conditions in a younger cohort, previously published by our group, revealed that results were not statistically different between the groups. Discussion: The OAT documentary and analysis showed that the suprasystolic pressure in the arm changed vasomotion in the forearm, displacing blood from the superficial to the deeper plexus vessels. Deflation allowed the blood to return and to be distributed in both plexuses. These responses were present in all individuals independent of their age. They appeared to be determined by the need to re-establish hemodynamics acutely modified by the challenger, which means that they were centrally mediated. Therefore, a new mechanistic interpretation of these exploratory maneuvers is required to better characterize in vivo cardiovascular physiology in humans.

Lower limb massage in humans increases local perfusion and impacts systemic hemodynamics.

Massage is commonly used as a complementary therapy for many different conditions. Demonstration of its physiological impact and understanding of its therapeutic mechanisms is still insufficient and often inconclusive. This study aims to characterize the physiological effects of effleurage, one of the most popular techniques, on human in vivo microcirculation and its impact on cardiovascular function. Two differently oriented variations of the technique, referred to influence physiological outcomes, were applied to 32 young (mean 19.8 ± 1.6 yr old) healthy volunteers of both sexes in a single, randomly chosen limb after informed written consent. Each protocol included a 10-min baseline (Phase I), a 5-min massage (Phase II), and a 10-min recovery (Phase III) register. A 30-min washout period separated both protocols. Perfusion was assessed by laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG), with their sensors applied distally in both feet. Blood pressure and pulse were also obtained. LDF signals were further analyzed in their components by the (Morlet) wavelet transform to probe the mechanisms involved. Results showed that effleurage consistently evoked a significant (P < 0.001) perfusion increase in the massaged limb, also visible in the contralateral limb (not significant) independently from the orientation (variant) used. No matter the perfusion differences known between sexes, the adaptive response was equivalent in both sexes. The component analysis of the LDF curves also suggests that these procedures, although brief and superficial, do modify multiple components of cardiovascular integration, with cardiac, respiratory, and myogenic components appearing to play a major role in reestablishing distal microcirculatory homeostasis.NEW & NOTEWORTHY The impact of effleurage, a well-known massage procedure used in human rehabilitation, in the lower limb hemodynamics, is demonstrated. When applied in a sole limb, massage increases skin microcirculatory flowmotion not only locally but also beyond, affecting systemic hemodynamics. This observation is an interesting example of the efficacy of cardiovascular integration mechanisms involving distal microcirculatory homeostasis. The proposed methodology allows a mechanistic view over skin flowmotion regulation, being applicable to further explore massage and its impact on microcirculatory physiology.

Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion.

Laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.