Observations on the perfusion recovery of regenerative angiogenesis in an ischemic limb model under hyperoxia

Abstract

This study combines two well‐known vascular research models, hyperoxia and hind limb ischemia, aiming to better characterize capacities of the hyperoxia challenge. We studied two groups of C57/BL6 male mice, a control (C) and a hind limb ischemia (HLI) group. Perfusion from both limbs was recorded in all animals by laser Doppler techniques under an oxygen (O2) saturated atmosphere, once for control and, during 35 days for the HLI group. We used a third set of normoxic animals for HLI morphometric control. The expected variability of responses was higher for the younger animals. In the HLI group, capillary density normalized at Day 21 as expected, but not microcirculatory physiology. In the operated limb, perfusion decreased dramatically following surgery (Day 4), as a slight reduction in the non‐operated limb was also noted. Consistently, the response to hyperoxia was an increased perfusion in the ischemic limb and decreased perfusion in the contralateral limb. Only at Day 35, both limbs exhibited similar flows, although noticeably lower than Day 0. These observations help to understand some of the functional variability attributed to the hyperoxia model, by showing (i) differences in the circulation of the limb pairs to readjust a new perfusion set‐point even after ischemia, an original finding implying that (ii) data from both limbs should be recorded when performing distal measurements in vivo. Our data demonstrate that the new vessels following HLI are not functionally normal, and this also affects the non‐operated limb. These findings confirm the discriminative capacities of the hyperoxia challenge and suggest its potential utility to study other pathologies with vascular impact.

Comparing the effects of human hind limb massage by analysis of Laser Doppler Flowmetry and Photoplethysmography signal components using the wavelet transform

“…In fact, this might already suggest that these two protocols have different impacts on the regional circulation, most probably related with the different mobilizations affecting perfusion toward (downward) or away (upward manouver) sensors. However, this analysis also confirms another intriguing, recently suggested, 27 feature-that the response to the massage in the test limb also impacts the contralateral limb. This is apparent in the example shown in Figure 2 where an increased perfusion, with lower magnitude, is noted in the contralateral limb a few moments after massage begins.…”

“…De fato, isto pode já sugerir que esses dois protocolos têm impactos diferentes na circulação regional, provavelmente relacionados com as diferentes mobilizações que se aproximam (manobra descendente) ou se afastam (manobra ascendente) dos sensores de perfusão. Entretanto, esta análise também confirma outra característica intrigante, recentemente sugerida 27 18 , eventualmente relacionada com a frequência de pulso e diminuição da pressão arterial encontrados com os sinais de FLD e FPG 7 . A diminuição dos componentes endoNOD e endoNOI durante a massagem para ambas as tecnologias e protocolos presumiria uma diminuição no fluxo sanguíneo no membro inferior, embora o aumento da componente miogénica e a diminuição simul-LDF and PPG Spearman component analysis showed weak to moderate correlations although the direction of the component response is generally coincident between the two technologies (Figures 3 and 4).…”

Exploring the perfusion modifications occurring with massage in the human lower limbs by non-contact polarized spectroscopy

“…This demands a permanent balance between hemodynamics and the organ's perfusion pressure, which represents the balance between arterial blood pressure and its determinants, e.g., heart rate, stroke volume and total peripheral vascular resistance 3 . This also means that a highly structured network of vessels arranged to optimize oxygen delivery to the tissues is needed, having in mind that oxygen is also a local regulatory element of these functions, influencing resistance, but also controlled by other local and systemic (homeostatic) regulators 4 . Neural inputs as hormones signal the central nervous system which modulate regional autonomic nervous system outflows.…”

“…Many other factors might be implied in this regulation since the endothelium itself, recently compared to an "airport hub" where all functions are intrinsically interconnected, attracts more of our attention in particular related with its role in vascular disease and as a potential therapeutic target 11 . Following some recent papers from our group 12 exploring new methodologies to assess in vivo microcirculatory physiology and pathophysiology, a potential cooperation between both limbs during the recovery period of an hindlimb procedure in the mouse 4 was described. An identical phenomenom was referred some years ago in human patients as part of a long-term vascular adaptation to ischemia due to peripheral arterial occlusive disease 13 .…”

“…Isso exige um equilíbrio permanente entre a hemodinâmica e a pressão de perfusão do órgão, que representa o equilíbrio entre a pressão arterial e seus determinantes, por exemplo, frequência cardíaca, volume sistólico e resistência vascular periférica total 3 . Isto também significa que é necessária uma rede altamente estruturada de vasos organizados para otimizar a entrega de oxigênio aos tecidos, tendo em mente que o oxigênio também é um elemento regulador local dessas funções, influenciando a resistência, mas também é controlado por outros reguladores locais e sistêmicos (homeostáticos) 4 . Os impulsos neuronais tal como as hormonas, sinalizam o sistema nervoso central que modula os fluxos regionais do sistema nervoso autônomo.…”