Renal denervation restores biomechanics of carotid arteries in a rat model of hypertension.

The prevalence of hypertension increases with aging and is associated with increased arterial stiffness. Resistant hypertension is presented when drug treatments fail to regulate a sustained increased blood pressure. Given that the mechanisms between the sympathetic nervous system and the kidney play an important role in blood regulation, renal denervation (RDN) has emerged as a therapeutic potential in resistant hypertension. In this study, we investigated the effects of RDN on the biomechanical response and microstructure of elastic arteries. Common carotid arteries (CCA) excised from 3-month, 8-month, and 8-month denervated rats were subjected to biaxial extension-inflation test. Our results showed that hypertension developed in the 8-month-old rats. The sustained elevated blood pressure resulted in arterial remodeling which was manifested as a significant stress increase in both axial and circumferential directions after 8 months. RDN had a favorable impact on CCAs with a restoration of stresses in values similar to control arteries at 3 months. After biomechanical testing, arteries were imaged under a multi-photon microscope to identify microstructural changes in extracellular matrix (ECM). Quantification of multi-photon images showed no significant alterations of the main ECM components, elastic and collagen fibers, indicating that arteries remained intact after RDN. Regardless of the experimental group, our microstructural analysis of the multi-photon images revealed that reorientation of the collagen fibers might be the main microstructural mechanism taking place during pressurization with their straightening happening during axial stretching.

Renal denervation restores biomechanics of carotid arteries in a rat model of hypertension.

The prevalence of hypertension increases with aging and is associated with increased arterial stiffness. Resistant hypertension is presented when drug treatments fail to regulate a sustained increased blood pressure. Given that the mechanisms between the sympathetic nervous system and the kidney play an important role in blood regulation, renal denervation (RDN) has emerged as a therapeutic potential in resistant hypertension. In this study, we investigated the effects of RDN on the biomechanical response and microstructure of elastic arteries. Common carotid arteries (CCA) were excised from 3-, 8- and 8-month-old denervated rats, and subjected to biaxial extension-inflation test. Our results showed that hypertension developed in the 8-month-old rats. The sustained elevated blood pressure resulted in arterial remodeling which was manifested as a significant stress increase in both axial and circumferential directions after 8 months. RDN had a favorable impact on CCAs with a restoration of stresses in values similar to control arteries at 3 months. After biomechanical testing, arteries were imaged under a multi-photon microscope to identify microstructural changes in extracellular matrix (ECM). Quantification of multi-photon images showed no significant alterations of the main ECM components, elastic and collagen fibers, indicating that arteries remained intact after RDN. Regardless of the experimental group, our microstructural analysis of the multi-photon images revealed that reorientation of the collagen fibers might be the main microstructural mechanism taking place during pressurization with their straightening happening during axial stretching.

Multiparametric non-linear TENS modulation to integrate intuitive sensory feedback.

Objective. Transcutaneous electrical nerve stimulation (TENS) has been recently introduced in neurorehabilitation and neuroprosthetics as a promising, non-invasive sensory feedback restoration alternative to implantable neurostimulation. Yet, the adopted stimulation paradigms are typically based on single-parameter modulations (e.g. pulse amplitude (PA), pulse-width (PW) or pulse frequency (PF)). They elicit artificial sensations characterized by a low intensity resolution (e.g. few perceived levels), low naturalness and intuitiveness, hindering the acceptance of this technology. To address these issues, we designed novel multiparametric stimulation paradigms, featuring the simultaneous modulation of multiple parameters, and implemented them in real-time tests of performance when exploited as artificial sensory inputs.Approach. We initially investigated the contribution of PW and PF variations to the perceived sensation magnitude through discrimination tests. Then, we designed three multiparametric stimulation paradigms comparing them with a standard PW linear modulation in terms of evoked sensation naturalness and intensity. The most performant paradigms were then implemented in real-time in a Virtual Reality-TENS platform to assess their ability to provide intuitive somatosensory feedback in a functional task.Main results. Our study highlighted a strong negative correlation between perceived naturalness and intensity: less intense sensations are usually deemed as more similar to natural touch. In addition, we observed that PF and PW changes have a different weight on the perceived sensation intensity. As a result, we adapted the activation charge rate (ACR) equation, proposed for implantable neurostimulation to predict the perceived intensity while co-modulating the PF and charge per pulse, to TENS (ACRT). ACRTallowed to design different multiparametric TENS paradigms with the same absolute perceived intensity. Although not reported as more natural, the multiparametric paradigm, based on sinusoidal PF modulation, resulted being more intuitive and subconsciously integrated than the standard linear one. This allowed subjects to achieve a faster and more accurate functional performance.Significance. Our findings suggest that TENS-based, multiparametric neurostimulation, despite not consciously perceived naturally, can provide integrated and more intuitive somatosensory information, as functionally proved. This could be exploited to design novel encoding strategies able to improve the performance of non-invasive sensory feedback technologies.