Ischemia-reperfusion injury in a rat microvascular skin free flap model: A histological, genetic, and blood flow study

Abstract

Ischemia reperfusion injury is associated with tissue damage and inflammation, and is one of the main factors causing flap failure in reconstructive microsurgery. Although ischemia-reperfusion (I/R) injury is a well-studied aspect of flap survival, its biological mechanisms remain to be elucidated. To better understand the biological processes of ischemia reperfusion injury, and to develop further therapeutic strategies, the main objective of this study was to identify the gene expression pattern and histological changes in an I/R injury animal model. Fourteen rats (n = 7/group) were randomly divided into control or ischemia-reperfusion group (8 hours of ischemia). Microsurgical anastomoses were objectively assessed using transit-time-ultrasound technology. Seven days after surgery, flap survival was evaluated and tissue samples were harvested for anatomopathological and gene-expression analyses.The I/R injury reduced the survival of free flaps and histological analyses revealed a subcutaneous edema together with an inflammatory infiltrate. Interestingly, the Arginase 1 expression level as well as the ratio of Arginase 1/Nitric oxide synthase 2 showed a significant increase in the I/R group. In summary, here we describe a well-characterized I/R animal model that may serve to evaluate therapeutic agents under reproducible and controlled conditions. Moreover, this model could be especially useful for the evaluation of arginase inhibitors and different compounds of potential interest in reconstructive microsurgery.

Dietary Nitrate Protects Against Skin Flap Ischemia-Reperfusion Injury in Rats via Modulation of Antioxidative Action and Reduction of Inflammatory Responses

“…The blocks were subsequently sectioned at 5 µm on the longitudinal plane and stained with hematoxylin and eosin (H&E) and Masson's Trichrome (MT). The main histologic outcome was scored for inflammatory cell infiltration, collagen deposition, edema, hemorrhage, thrombosis, and hair follicle destruction as follows: (0) absent, (1) mild, (2) moderate, (3) severe (Ballestin et al, 2018). At least five microscopic areas were examined to score each specimen, and the total damage scores were calculated as the sum of the scores given for each criterion (Iseri et al, 2008).…”

Effects of Ischemic Preconditioning and C1 Esterase Inhibitor Administration following Ischemia-Reperfusion Injury in a Rat Skin Flap Model

“…The selected time for primary ischemia was 8 hours, based on previous studies and our own research experience with this animal model. 2,11,[14][15][16] Macroscopically, our study results showed a significant decrease in flap survival in the I/R control group compared with the control group (p < 0.05). These results conflicted with the histological findings as higher levels of edema formation (p < 0.05), neutrophil infiltration (p < 0.05), and structural damage were observed in the I/R group than in the control group.…”

NIR-II Fluorescence Imaging of Skin Avulsion and Necrosis

“…As previously reported, skin avulsion leads to damage to soft tissues and blood vessels, which may be associated with different biological processes including ischemia and hypoxia (Ballestin et al, 2018). Therefore, apoptosis pathways mediated by caspase-3 are induced and may exert an immediate influence on the viability of the avulsed skin (Liu et al, 2015).…”