This hyperoxia mouse model using the wavelet transform analysis of flowmotion signals helps to look further into microvascular dysfunction

Abstract

The use of animal models still presents many difficulties mostly because (a) no single model accurately recreates one disease, (b) the use of so many models impair comparison of results and (c) extrapolation to human is very limited. We have been dedicated to develop the potential use of oxygen as a challenger to study microcirculatory function and regulatory mechanisms. In the present study we show how this hyperoxia mouse model helps to identify different events associated to angiogenesis, following an hindlimb ischemia procedure, and test its discriminative capacities in detecting relevant differences in microvascular function between healthy and non‐healthy mice. Animals (n=66) were divided in three groups ‐ Control (C) with 33 C57/BL6 non‐transgenic male mice, part of which (9) submitted to a hindlimb ischemia (HLI) procedure, a genetically modified diabetic group (DB) including 8 transgenic C57BLKsJ‐db/db obese diabetic mice and the corresponding internal control of 8 age‐matched C57BLKsJ‐db/+ mice, and a transgenic cardiac hypertrophy group (CH) with 9 BALB/c mice prone to develop cardiac failure and 8corresponding age‐matched internal controls. Animals were anesthetized with a ketamine ‐ xylazine mixture and perfusion data collect by Laser Doppler Flowmetry during baseline rest (Phase 1), while breathing a 100% oxygen atmosphere (Phase2) and during recovery (Phase 3) and compared. Laser Doppler (LD) imaging and flowmetry were used as assessment instruments allowing to follow up all the processes regarding the HLI recovery. The wavelet transform (WT) component's analysis was allowed to further distinct between groups. Hyperoxia by itself revealled that new vessels are not functionally equivalent to those in the non‐operated limb but that recovery, also involves this limb, suggesting a cooperation mechanism probably centrally mediated. The WT analysis suggests that cardiorespiratory, myogenic and endothelial components act as main markers. In DB group db/+ animals behave as the Control group, as expected, but WT analysis shown significant differences for myogenic and the endothelial components. Noteworthy was the increase of the sympathetic components in the db/db set, as in the NHE1‐OE animals, in both cases reported as a main component of these pathophysiological processes. In conclusion, this hyperoxia‐mouse model, including the WT component analysis of LDF signal, seems to be reproducible, robust and discriminative, providing a deeper look into these different expressions of microcirculatoru pathophysiology in different experimental conditionsSupport or Funding InformationThis work was supported by national funds from FCT I.P, within the project UID/DTP/04567/2016.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.