Cutaneous and renal vasodilatory response to local pressure application: A comparative study in mice.

BACKGROUND AND AIM: We have reported a novel relationship involving mechanical stimulation and vasodilation in rodent and human skin, referred to as pressure-induced vasodilation (PIV). It is unknown whether this mechanism exists in kidney and reflects the microcirculation in deep organs. Therefore, we compared the skin and kidney PIV to determine whether their changes were similar. METHODS: In anesthetized mice fed a normal salt-diet, laser Doppler flux (LDF) signals were measured when an increase in local pressure was applied to the surface of the head skin with the rate of 2.2Pa/s (1mmHg/min) and to the left kidney with a rate of 4.4Pa/s (2mmHg/min). The mechanism underlying renal PIV was also investigated. The skin and kidney PIV were also compared during salt load (4% NaCl diet). RESULTS: The kidney had higher baseline LDF and vascular conductance compared to those of the skin. Pressure application increased the LDF in the kidney as well as in the skin with a comparable maximal magnitude (about 25% from baseline value), despite different kinetics of PIV evolution. As we previously reported in the skin, the kidney PIV response was mediated by the activation of transient receptor potential vanilloid type 1 channels, the release of calcitonin gene-related peptide, and the participation of prostaglandins and nitric oxide. In the absence of hypertension, high salt intake abolished the cutaneous PIV response and markedly impaired the renal one. CONCLUSION: PIV response in the mouse kidney results from a neuro-vascular interaction. Despite some differences between the skin and the kidney PIV, the similarities in their response and signaling mechanisms suggest that the cutaneous microcirculation could reflect, in part, the microcirculation of the renal cortex.

Blood flow responses over sacrum in nursing home residents during one hour bed rest.

OBJECTIVES: To describe individual BF responses in a nursing home resident population for one-hour periods of bed rest. METHODS: BF was measured for one hour over the sacrum in 0° supine position and 30° supine tilt position in 25 individuals aged 65 y or older while lying on a pressure-redistributing mattress. Measurements were made at three tissue depths (1, 2, and 10 mm) using the noninvasive optical techniques, LDF and PPG. RESULTS: Eleven participants had a PIV response at 1 mm depth in both positions and seven participants had a lack of this response at this depth and positions. The BF response at 1 mm depth appeared immediately and remained over, or below, baseline for the entire 60 min of loading in both positions. These BF patterns were also seen in deeper tissue layers. CONCLUSIONS: The cutaneous BF response among the nursing home residents was distinct, appeared early, and remained during the one hour of loading.

Microcirculatory responses of sacral tissue in healthy individuals and inpatients on different pressure-redistribution mattresses.

OBJECTIVE: The aim of this study was to explore the interaction between interface pressure, pressure-induced vasodilation, and reactive hyperaemia with different pressure-redistribution mattresses. METHOD: A cross-sectional study was performed with a convenience sample of healthy young individuals, and healthy older individuals and inpatients, at a university hospital in Sweden. Blood flow was measured at depths of 1mm, 2mm, and 10mm using laser Doppler flowmetry and photoplethysmography. The blood flow, interface pressure and skin temperature were measured in the sacral tissue before, during, and after load while lying on one standard hospital mattress and three different pressure-redistribution mattresses. RESULTS: There were significant differences between the average sacral pressure, peak sacral pressure, and local probe pressure on the three pressure-redistribution mattresses, the lowest values found were with the visco-elastic foam/air mattress (23.5 ± 2.5mmHg, 49.3 ± 11.1mmHg, 29.2 ± 14.0mmHg, respectively). Blood flow, measured as pressure-induced vasodilation, was most affected in the visco-elastic foam/air group compared to the alternating pressure mattress group at tissue depths of 2mm (39.0% and 20.0%, respectively), and 10mm (56.9 % and 35.1%, respectively). Subjects in all three groups, including healthy 18-65 year olds, were identified with no pressure-induced vasodilation or reactive hyperaemia on any mattress (n=11), which is considered a high-risk blood flow response. CONCLUSION: Interface pressure magnitudes considered not harmful during pressure-exposure on different pressure-redistribution mattresses can affect the microcirculation in different tissue structures. Despite having the lowest pressure values compared with the other mattresses, the visco-elastic foam/air mattress had the highest proportion of subjects with decreased blood flow. Healthy young individuals were identified with the high-risk blood flow response, suggesting an innate vulnerability to pressure exposure. Furthermore, the evaluation of pressure-redistribution support surfaces in terms of mean blood flow during and after tissue exposure is not feasible, but assessment of pressure-induced vasodilation and reactive hyperaemia could be a new way to assess individualised physiological measurements of mechanisms known to be related to pressure ulcer development.

Pressure-induced vasodilation and reactive hyperemia at different depths in sacral tissue under clinically relevant conditions.

OBJECTIVE: To characterize PIV and RH at different sacral tissue depths in different populations under clinically relevant pressure exposure. METHODS: Forty-two subjects (<65 years), 38 subjects (≥65 years), and 35 patients (≥65 years) participated. Interface pressure, skin temperature, and blood flow at tissue depths of 1, 2, and 10 mm (using LDF and PPG) were measured in the sacral tissue before, during, and after load in a supine position. RESULTS: Pressure-induced vasodilation and RH were observed at three tissue depths. At 10 mm depth, the proportion of subjects with a lack of PIV was higher compared to superficial depths. The patients had higher interface pressure during load than the healthy individuals, but there were no significant differences in blood flow. Twenty-nine subjects in all three study groups were identified with a lack of PIV and RH. CONCLUSIONS: Pressure-induced vasodilation and RH can be observed at different tissue depths. A lack of these responses was found in healthy individuals as well as in patients indicating an innate susceptibility in some individuals, and are potential important factors to evaluate in order to better understand the etiology of pressure ulcers.

Alpha-Lipoic Acid Supplementation Restores Early Age-Related Sensory and Endothelial Dysfunction in the Skin.

Many changes characterize skin aging, and the resulting dysfunctions still constitute a real challenge for our society. The aim of this study was to compare the skin aging of two rat strains, Wistar and Brown Norway (BN), considered as "poorly aging" and "healthy aging" models, respectively, and to assess the effect of alpha-lipoic acid (LPA), especially on skin microcirculation. To this purpose, various skin characteristics were studied at 6, 12, and 24 months and compared to the results of LPA treatment performed at 12 or 24 months. Skin aging occurred in both strains, but we showed an early occurrence of different age-related disorders in the Wistar strain compared to BN strain, especially regarding weight gain, glycemia dysregulation, basal skin perfusion, endothelial function, and skin resistance to low pressure. LPA treatment tended to improve skin resistance to low pressure in BN but not in Wistar despite the improvement of basal skin perfusion, endothelial function, and skin sensory sensitivity. Overall, this study confirmed the healthier aging of BN compared to Wistar strain and the positive effect of LPA on both general state and skin microcirculation.

The Role of Cutaneous Microcirculatory Responses in Tissue Injury, Inflammation and Repair at the Foot in Diabetes.

Diabetic foot syndrome is one of the most costly complications of diabetes. Damage to the soft tissue structure is one of the primary causes of diabetic foot ulcers and most of the current literature focuses on factors such as neuropathy and excessive load. Although the role of blood supply has been reported in the context of macro-circulation, soft tissue damage and its healing in the context of skin microcirculation have not been adequately investigated. Previous research suggested that certain microcirculatory responses protect the skin and their impairment may contribute to increased risk for occlusive and ischemic injuries to the foot. The purpose of this narrative review was to explore and establish the possible link between impairment in skin perfusion and the chain of events that leads to ulceration, considering the interaction with other more established ulceration factors. This review highlights some of the key skin microcirculatory functions in response to various stimuli. The microcirculatory responses observed in the form of altered skin blood flow are divided into three categories based on the type of stimuli including occlusion, pressure and temperature. Studies on the three categories were reviewed including: the microcirculatory response to occlusive ischemia or Post-Occlusive Reactive Hyperaemia (PORH); the microcirculatory response to locally applied pressure such as Pressure-Induced Vasodilation (PIV); and the interplay between microcirculation and skin temperature and the microcirculatory responses to thermal stimuli such as reduced/increased blood flow due to cooling/heating. This review highlights how microcirculatory responses protect the skin and the plantar soft tissues and their plausible dysfunction in people with diabetes. Whilst discussing the link between impairment in skin perfusion as a result of altered microcirculatory response, the review describes the chain of events that leads to ulceration. A thorough understanding of the microcirculatory function and its impaired reactive mechanisms is provided, which allows an understanding of the interaction between functional disturbances of microcirculation and other more established factors for foot ulceration.

Alteration of Pressure-Induced Vasodilation in Aging and Diabetes, a Neuro-Vascular Damage.

Skin is constantly subjected to pressure at different levels. Pressure-induced vasodilation (PIV) is one of the response mechanisms to low pressure that maintains the homeostasis of the skin. PIV results from the interaction of primary afferent nerves and vascular endothelium of skin vessels. Thanks to this cutaneous neuro-vascular interaction, the cutaneous blood flow increase allows the maintenance of an optimal level of oxygenation and minimizes the lack of vascularization of the skin tissue under low pressure. It seems to be associated with the cutaneous protection mechanisms to prevent pressure ulcers. In some contexts, where microangiopathy and neuropathy can occur, such as aging and diabetes, PIV is impaired, leading to a dramatic early decrease in local skin blood flow when low pressure is applied. In aging, PIV alteration is due to endothelial dysfunction, essentially from an alteration of the nitric oxide pathway. In the inflamm-aging context, oxidative stress increases leading to endothelial cell and nerve damages. An age-related sensory neuropathy will exacerbate the alteration of PIV during the aging process. In diabetes, non-controlled hyperglycaemia leads to an increase in several pathological biochemical pathways that involve oxidative stress and can affect PIV. Sorbinil, alagebrium and alpha-lipoic acid are able individually to restore PIV through a possible oxidative stress reduction. Candesartan, an angiotensin II type 1 receptor blocker, is also able to restore PIV and prevent pressure ulcer formation. The possibility of preventing pressure ulcer associated to diabetes and/or aging with the restoration of PIV seems to be a promising research path.