Aging effects on pedicled fasciocutaneous flap survival in rats

Roy, Sudeep; Aksamitiene, Edita; Hota, Salini; Zhang, Lihui; Sciarrino, Joseph; Baker, Adam; Heffelfinger, Ryan; Tuluc, Madalina; Hoek, Jan B.; Pribitkin, Edmund A.

doi:10.1002/hed.24181

Cited by 7 publications

(3 citation statements)

References 41 publications

(77 reference statements)

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“…38 VEGF is vital to angiogenesis, playing an important role in flap survival. 39–41 In our study, VEGF expression was higher in the EVPP group than in the EVPL group. We were unable to determine the precise mechanism of angiogenesis in the choke zones in this study; however, our results suggest that an increase in VEGF expression may be essential for angiogenesis and vasodilation in the choke zones, which is consistent with past research.…”

Section: Discussionsupporting

confidence: 45%

Extrinsic Vascular Pathway Preservation Improves Survival in a Rat Three-Territory Flap Model Based on the Deep Circumflex Iliac Artery

Xie,

Wang,

Zang

et al. 2023

Plastic &Amp; Reconstructive Surgery

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arious extended flaps have been widely used in clinical settings; however, unexpected necrosis remains common in the distal portion of the flap. 1,2 In 2013, a review of 693 articles on 17,096 deep inferior epigastric perforator flaps showed that the flap necrosis rate was 0% to 11%. 3 Similarly, a 2015 retrospective study of 45 patients who underwent extended thoracodorsal artery perforator flap surgery for breast reconstruction reported that the distal flap necrosis rate was 13%. 4 A retrospective study on 150 patients who underwent extended circumflex scapular flap for neck burn reconstruction from 1986 to 2015 reported a distal flap necrosis rate of 15%. 5 Various therapeutic modalities have been used to augment tissue perfusion and improve flap Background: Extended flaps are commonly applied for large defects. However, a postoperative flap necrosis incidence of 11% to 44% remains a major complication. Previous clinical studies have shown that maintaining the extrinsic vascular pathway (EVP) can increase the survival area of extended flaps. The authors hypothesized that preserving the EVP would improve flap survival by reducing blood resistance within the vascular territory. Methods: Twenty-four adult male Sprague-Dawley rats were used. Tissue samples were obtained from eight untreated rats as a baseline control. Three-territory flaps were elevated in the remaining 16 rats. The EVP was preserved or ligated. Flap perfusion was assessed immediately using indocyanine green angiography. Rats were euthanized on day 7. The flap survival area was measured using Adobe Photoshop. Hematoxylin and eosin staining, CD31 immunostaining, and Western blot analysis of vascular endothelial growth factor protein expression were used to quantitatively assess vasodilation and angiogenesis in choke zones. Results: Indocyanine green angiography revealed that blood could flow through the preserved EVP and perfuse the third vascular territory of the flap. EVP preservation significantly increased flap survival area (86.3%, 19.3% difference; P < 0.001), promoted vasodilation (5.0/choke zone, 3.0/choke zone difference; P = 0.013) and angiogenesis (29.3/mm 2 , 14.3/mm 2 difference; P = 0.002), and increased vascular endothelial growth factor expression (0.6, 0.2 difference; P = 0.067) in the second choke zone. Conclusions: EVP preservation improves flap survival in this rat three-territory flap model. Further investigation in large-animal models is required for clinical translation.

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Section: Discussionsupporting

confidence: 45%

Extrinsic Vascular Pathway Preservation Improves Survival in a Rat Three-Territory Flap Model Based on the Deep Circumflex Iliac Artery

Xie,

Wang,

Zang

et al. 2023

Plastic &Amp; Reconstructive Surgery

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“…This experimental prospective study was conducted on two groups of male albino rats. The rats were selected based on animal research center recommendations and previous studies (Sherif, 2014;Wang et al, 2014;Elsharkawy and Alhazzazi, 2016;Roy et al, 2016) Thus, we selected 20 rats for each group, and each sample was prepared for about 50 histological sections. Group I consisted of 20 adult rats aged about six months and weighing between 150-200 g, whereas Group II included 20 rats aged one year weighing between 250-300 g. The animals were fed on a diet consisting of ground barley, full cream powdered milk, and fresh vegetables.…”

Section: Methodsmentioning

confidence: 99%

Age-Dependent Differential Expression of Apoptotic Markers in Rat Oral Mucosa

Elias

2018

Asian Pac J Cancer Prev

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Objective:This study tests the hypothesis that gingival tissue produces age-dependent activation of apoptotic markers.Methods:To address the hypothesis, a prospective experimental study was conducted on 20 adult male albino rats, which were divided into two groups. Group 1 comprised rats aged six months (weighing 150–200 g), and group 2 included old rats aged one year (weighing 250–300 g). Gingival tissue and buccal mucosa biopsy samples were obtained from both groups. Histological and immunohistochemical (Bax apoptotic protein marker) sections were analyzed for both groups.Results:Our data showed a significant decrease in the proliferative activity of oral mucosa (gingiva and buccal mucosa) in old rats and an increase in the immunoreactivity of Bax apoptotic proteins related to increased susceptibility of cells to apoptosis. The mucosal structures (epithelium and lamina propria) were significantly different between the two groups. Furthermore, immunoreactivity for Bax was different between young and old rats.Conclusions:Aging is associated with changes that lead to progressive, irreversible deterioration of the functional capacities of several tissues and organs. Our study demonstrated the effect of age on the histological and apoptotic behavior of oral mucosa (gingiva and buccal mucosa) cells.

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“…Sometimes the investigators aim to mimic severe medical complications (e.g., vascular thrombosis, edema, ulcerative and infected wounds) [ 39 ] or reproduce well-known comorbidities (e.g., obesity, diabetes, ageing, smoking, alcohol intake etc.) [ 40 – 42 ] or stimulatory responses (e.g. exercise) [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing

Aksamitiene,

Heffelfinger,

Hoek

et al. 2024

Biol Proced Online

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Background Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure. Results Unlike in the most frequently used classical unilateral McFarlane’s caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap—under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. Conclusions This technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification. Graphical Abstract

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Aging effects on pedicled fasciocutaneous flap survival in rats

Abstract: Pedicled flap survival is higher in younger rats in part because of unhindered expression of VEGF and enhanced activity of cell survival and promigratory signaling pathways. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1152-E1162, 2016.

Cited by 7 publications

References 41 publications

Extrinsic Vascular Pathway Preservation Improves Survival in a Rat Three-Territory Flap Model Based on the Deep Circumflex Iliac Artery

Extrinsic Vascular Pathway Preservation Improves Survival in a Rat Three-Territory Flap Model Based on the Deep Circumflex Iliac Artery

Age-Dependent Differential Expression of Apoptotic Markers in Rat Oral Mucosa

Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing

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