Influence of cutaneous and muscular circulation on spatially resolved versus standard Beer-Lambert near-infrared spectroscopy

The potential interference of cutaneous circulation on muscle blood volume and oxygenation monitoring by near‐infrared spectroscopy (NIRS) remains an important limitation of this technique. Spatially resolved spectroscopy (SRS) was reported to minimize the contribution of superficial tissue layers in cerebral monitoring but this characteristic has never been documented in muscle tissue monitoring. This study aims to compare SRS with the standard Beer–Lambert (BL) technique in detecting blood volume changes selectively induced in muscle and skin. In 16 healthy subjects, the biceps brachii was investigated during isometric elbow flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed before and after exposure of the upper arm to warm air flow. From probes applied over the muscle belly the following variables were recorded: total hemoglobin index (THI, SRS‐based), total hemoglobin concentration (tHb, BL‐based), tissue oxygenation index (TOI, SRS‐based), and skin blood flow (SBF), using laser Doppler flowmetry. Blood volume indices exhibited similar changes during muscle contraction but only tHb significantly increased during warming (+5.2 ± 0.7 μmol/L·cm, an effect comparable to the increase occurring in postcontraction hyperemia), accompanying a 10‐fold increase in SBF. Contraction‐induced changes in tHb and THI were not substantially affected by warming, although the tHb tracing was shifted upward by (5.2 ± 3.5 μmol/L·cm, P < 0.01). TOI was not affected by cutaneous warming. In conclusion, SRS appears to effectively reject interference by SBF in both muscle blood volume and oxygenation monitoring. Instead, BL‐based parameters should be interpreted with caution, whenever changes in cutaneous perfusion cannot be excluded

A novel pneutronic device for the investigation of compression-induced physiological phenomena: Modeling and experimental testing

An automatic pneumatic system designed to investigate the physiological effects induced by limb compressions, able to apply customizable pressure patterns in the physiologic range (0–200 mmHg), is here presented. A mathematical model, simulating the whole pneutronic system and its interaction with the limb is described. The model is validated by means of experimental tests. An on-going study aiming to investigate the role of different factors in the development of post compression hyperemia is presented

Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions (n = 3-6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo- Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4) the extent of attenuation negatively correlates with tissue oxygenation (r=-0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3) the extent of attenuation of the compression- induced hyperemia is proportional to the level of oxygenation achieved in the tissue. The results support the concept that tissue oxygenation is a key variable in blood flow regulation. © 2017 the American Physiological Society

Design and Simulation of a Novel Pneumotronic System Aimed to the Investigation of Vascular Phenomena Induced by Limb Compression

Intermittent Pneumatic Compression (IPC) devices can be used to analyze the mechanisms underlying several vascular phenomena, such as hyperaemia. Commercial devices have limited dynamics and do not allow the delivery of customizable compressive pressure patterns, making the analysis of such phenomena difficult, which may require the application of long stimulations with low amplitude as well as fast compressions with higher pressure level. To overcome these issues, a novel pneumotronic device aimed to the investigation of the physiological effects induced by limb compressions is conceived and presented in this work. The design requirements of the system, capable of delivering customizable compressive patterns in the range 0 mmHg - 200 mmHg, are outlined. The final prototype architecture is described, and a mathematical model of the entire system, also including the interaction between the device and the limb tissues, is proposed. The performance of the device was evaluated in several conditions by means of simulations, whose results were compared to the data collected from experimental trials in order to validate the model. The outcomes of both experimentation and simulation trials proved the effectiveness of the solution proposed. A possible employment of this device for the investigation of the rapid compression-induced hyperaemia is presented. Other potential applications concern the wide range of intermittent-pneumatic compression treatments

Hyper-Oxygenation Attenuates the Rapid Vasodilatory Response to Muscle Contraction and Compression

A single muscle compression (MC) with accompanying hyperemia and hyper-oxygenation results in attenuation of a subsequent MC hyperemia, as long as the subsequent MC takes place when muscle oxygenation is still elevated. Whether this is due to the hyper-oxygenation, or compression-induced de-activation of mechano-sensitive structures is unclear. We hypothesized that increased oxygenation and not de-activation of mechano-sensitive structures was responsible for this attenuation and that both compression and contraction-induced hyperemia attenuate the hyperemic response to a subsequent muscle contraction, and vice-versa. Protocol-1) In eight subjects two MCs separated by a 25 s interval were delivered to the forearm without or with partial occlusion of the axillary artery, aimed at preventing hyperemia and increased oxygenation in response to the first MC. Tissue oxygenation [oxygenated (hemoglobin + myoglobin)/total (hemoglobin + myoglobin)] from forearm muscles and brachial artery blood flow were continuously monitored by means of spatially-resolved near-infrared spectroscopy (NIRS) and Doppler ultrasound, respectively. With unrestrained blood flow, the hyperemic response to the second MC was attenuated, compared to the first (5.7 ± 3.3 vs. 14.8 ± 3.9 ml, P &lt; 0.05). This attenuation was abolished with partial occlusion of the auxillary artery (14.4 ± 3.9 ml). Protocol-2) In 10 healthy subjects, hemodynamic changes were assessed in response to MC and electrically stimulated contraction (ESC, 0.5 s duration, 20 Hz) of calf muscles, as single stimuli or delivered in sequences of two separated by a 25 s interval. When MC or ESC were delivered 25 s following MC or ESC the response to the second stimulus was always attenuated (range: 60–90%). These findings support a role for excess tissue oxygenation in the attenuation of mechanically-stimulated rapid dilation and rule out inactivation of mechano-sensitive structures. Furthermore, both MC and ESC rapid vasodilatation are attenuated by prior transient hyperemia, regardless of whether the hyperemia is due to MC or ESC. Previously, mechanisms responsible for this dilation have not been considered to be oxygen sensitive. This study identifies muscle oxygenation state as relevant blunting factor, and reveals the need to investigate how these feedforward mechanisms might actually be affected by oxygenation

Delivery of customizable compressive patterns to human limbs to investigate vascular reactivity

Objective: Commercial devices for pneumatic compressive treatment of the limbs generally provide predefined stereotyped compressive profiles. The possibility to deliver compressive stimuli with a customizable pressure profile would be useful to differently probe the vascular reactivity to muscle compression (MC) and improve the understanding of MC-induced hyperemia. Aim of this study was the realization of a novel pneumatic system capable of generating adjustable and stable compressive conditions, preceding and following a ‘standard’MC stimulus. Approach: A custom-made pneumatic system specifically built to this purpose is tested and characterized in 10 subjects. Three different compressive patterns were delivered to the leg: (1) a constant level: 50mmHg for 50 s; (2) MC: 200mmHg for 1 s; (3) a complex profile: 20mmHg for 50 s, 200mmHg for 1 s, 50mmHg for 50 s. Main results: The implemented system allowed to deliver graded compressions to the limb characterized by fast transitions (0 to 200mmHg in 0.5±0.07 s) and stable plateau levels (50.4±0.5mmHg). Significance: A new, low-cost, pneumatic prototype has been presented and tested in the present study allowing to deliver compressive stimuli with pre-and post-compressions of adjustable level.This device has been conceived for research purposes and may find application in therapeutic compressive treatments

Synthesis, biophysical characterization and anti-HIV activity of d(TG3AG) Quadruplexes bearing hydrophobic tails at the 5'-end

Novel conjugated G-quadruplex-forming d(TG3AG) oligonucleotides, linked to hydrophobic groups through phosphodiester bonds at 5'-end, have been synthesized as potential anti-HIV aptamers, via a fully automated, online phosphoramidite-based solid-phase strategy. Conjugated quadruplexes showed pronounced anti-HIV activity with some preference for HIV-1, with inhibitory activity invariably in the low micromolar range. The CD and DSC monitored thermal denaturation studies on the resulting quadruplexes, indicated the insertion of lipophilic residue at the 5'-end, conferring always improved stability to the quadruplex complex (20<ΔTm<40°C). The data suggest no direct functional relationship between the thermal stability and anti-HIV activity of the folded conjugated G-quartets. It would appear that the nature of the residue at 5' end of the d(TG3AG) quadruplexes plays an important role in the thermodynamic stabilization but a minor influence on the anti-HIV activity. Moreover, a detailed CD and DSC analyses indicate a monophasic behaviour for sequences I and V, while for ODNs (II-IV) clearly show that these quadruplex structures deviate from simple two-state melting, supporting the hypothesis that intermediate states along the dissociation pathway may exist.status: publishe