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E Uhl

Publications and source records attributed to E Uhl.

57 records · Page 4Linked to original sources

The hairless mouse ear: an in vivo model for studying wound neovascularization.

Microvascular ingrowth into damaged tissue is an essential component of the normal healing process. In fact, wound therapy is often aimed at promoting neovascularization. However, little is known about the mechanisms that regulate microvascular ingrowth into a healing wound. This limited knowledge is largely due to the lack of adequate models in which microvascular ingrowth can be quantitatively analyzed throughout the healing process. To address this deficiency, we developed a model in which a wound was created on the ear of the hairless mouse-a well established model for directly viewing and measuring skin microcirculation. While the animals were under ketamine and xylazine anesthesia, 2.25 mm diameter full-thickness wounds were created on the dorsum of hairless mouse ears down to but not including the cartilage (0.125 mm depth). With the use of video microscopy and computer-assisted digitized planimetry, the precise epithelial and neovascular wound edge was viewed and measured regularly throughout healing. Therefore, this model can provide objective data on wound epithelialization and neovascularization throughout healing. This model was used to examine the effect of topical wound agents on epithelialization and neovascularization. Differential effects by these anti-microbial agents on these two processes were observed, which suggests clinical implications for their use.

Journal Article↗

Expression of mRNA for phospholipase A2, cyclooxygenases, and lipoxygenases in cultured human umbilical vascular endothelial and smooth muscle cells and in biopsies from umbilical arteries and veins.

Arachidonic acid (AA) is released by phospholipase A2 (PLA2) and then converted into vasoactive and inflammatory eicosanoids by cyclooxygenases (COX) and lipoxygenases (LOX). These eicosanoids are important paracrine regulators of vascular permeability, blood flow, local pro- and anticoagulant activity and they play a major role in the local inflammatory response. We have investigated the presence of mRNAs for PLA2 and for isoforms of COX and LOX in both human endothelial cells (EC) and in human smooth muscle cells (SMC) in culture and in vascular biopsies of human umbilical veins (HUVB) and arteries (HUAB) by using the reversed transcription-polymerase chain reaction (RT-PCR) technique. Results show detectable levels of PLA2 type IV (cPLA2) in cultured EC and SMC and in vascular wall biopsies from HUAB and HUVB. The cultured EC and SMC demonstrate higher levels of both COX-1 and COX-2 with PCR analyses than do vascular wall biopsies from HUAB and HUVB. This indicates a difference in the native expression of COX-1 and COX-2 in cultures of EC and SMC compared to that in biopsies from intact vessel walls. The EC and SMC in culture do not express mRNA for 5-LOX, that was, however, expressed in the vascular wall biopsies. This speaks in favour of a constitutive, i.e. in vivo expression of 5-LOX in SMC in the vascular wall of both umbilical vein and arteries. Thus results from in vitro studies of constitutive COX and LOX expression in EC and vascular SMC in culture cannot simply be extrapolated to represent in vivo conditions.

Biopsy↗

Influence of ketamine and pentobarbital on microvascular perfusion in normal skin and skin flaps.

The influence of two anesthetics, ketamine and sodium pentobarbital, on the microvascular perfusion of normal skin and skin flaps was evaluated by the use of a laser Doppler perfusion imager which allows the rapid scanning of tissue perfusion. Arterial skin flaps with a distal random random portion were created on the ears of hairless mice (n = 20), and perfusion was measured in the proximal, central, and distal parts of the flap. No differences in microvascular perfusion throughout the whole experiment were found between the ketamine and the pentobarbital group. In normal skin microvascular perfusion decreased to 83-73% of baseline values after induction of anesthesia. After flap creation, the perfusion was further reduced in the distal and central parts of the flap to 48-43% of baseline values, whereas no significant change was found in the proximal part. Six hours after flap creation, with the animal awake, perfusion had increased again in all parts of the flap, remaining at a constant level during the rest of the experiment. Anesthesia had less effects on microvascular perfusion in skin flaps as observed 1 day after flap creation. Perfusion of the central and distal parts of the flap decreased by 10-16%, whereas, in contrast to normal skin, the proximal part remained unaffected. Our study shows that baseline measurements are required in skin flap models when the microvascular perfusion in skin flaps is analyzed under general anesthesia.

Animals↗