Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps

Schweizer, Dennis; Schweizer, Riccardo; Zhang, Shengye; Kamat, Pranitha; Contaldo, Claudio; Rieben, Robert; Eberli, Daniel; Giovanoli, Pietro; Erni, Dominique; Plock, Jan A.

doi:10.1016/j.jss.2013.04.004

Cited by 55 publications

(38 citation statements)

References 36 publications

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“…In fact, the effect of muscle relaxation has made it helpful in the management of hemifacial spasm, strabismus, and blepharospasm 14 . Botulinum toxin type A has been recently studied as a vasodilator agent in experimental and clinical studies as this neurotoxin has also been successfully used in the management of Raynaud's phenomenon and preventive on vasospasm following microvascular anastomosis [11][12][13] . Two mechanisms have been described for the inhibitory effect of BoNTA on vasospasm: inhibition of sympathetically mediated vasospasm in cold environment and prevention of vascular smooth muscle receptor recruitment 15,16 .…”

Section: Discussionmentioning

confidence: 99%

“…Preventive effect of BoNTA on skin flap necrosis has been reported in only few experimental studies [11][12][13] . Its use on other clinical conditions, such as vascular diseases, remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…However, modalities that specifically target the flap have shown mixed results [5][6][7] . Experimental models of skin flap necrosis have been employed to study the clinical conditions that increase risk 8 as well as to evaluate strategies that improve flap survival, such as vasodilators [9][10][11] . Nevertheless, few studies have evaluated the effect of botulinum toxin type A (BoNTA) in skin flap viability.…”

Section: Introductionmentioning

confidence: 99%

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Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

et al. 2015

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PURPOSE:To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats. METHODS:Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded. RESULTS:Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs 0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs 0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871).Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups. CONCLUSIONS:Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day.Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group.BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

et al. 2015

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“…In in vitro assays, several reports demonstrated that BTX-A enhanced the blood flow and survival of ischemic skin flaps using animal cutaneous flap models20212223. With respect to I/R injury and BTX-A, Küçüker et al showed that BTX-A application suppressed apoptosis and the tissue levels of malonyl dialdehyde (MDA) and nitric oxide end products (NOx) in a rat model of skeletal muscle I/R injury24.…”

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confidence: 99%

Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury

Uchiyama

Yamada

Perera

et al. 2015

Sci Rep

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Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the synaptic space, and has been clinically used for aesthetic indications, neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that BTX-A enhanced the blood flow and improved ischemia in animal models. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The number of CD31+ vessels and αSMA+ pericytes or myofibroblasts in wounds were significantly increased in the I/R mice treated with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. In an in vitro assay, BTX-A significantly prevented the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in vascular endothelial cells. Furthermore, the administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. Exogenous application of BTX-A might have therapeutic potential for cutaneous I/R injuries.

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“…The perfusion rate was set to 1 µl/minute as described previously. 25,26 The probes were perfused for 30 minutes for equilibration before sample collection. Dialysates were stored at −80°C and analyzed for RANTES.…”

Section: Microdialysismentioning

confidence: 99%

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

Kamat

Schweizer

Kaenel

et al. 2015

Plastic and Reconstructive Surgery

Self Cite

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BACKGROUND: Stem cell-enriched fat grafting has been proposed as a potential therapy for reconstructive, restorative, or enhancement-related procedures of the breast. Its role in postoncologic breast reconstruction is still emerging, with concerns about safety. The authors investigated the dose-dependent interaction between human adipose-derived mesenchymal stromal cells (AD-MSCs) and human breast cancer cell (BCC) lines [MDA-MB-231 (MDA) and MCF-7 (MCF)] focusing on tumor microenvironment, tumor growth, and metastatic spread. METHODS: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC/(MDA/MCF), and AD-MSC/(MDA/MCF)]. A humanized orthotopic murine cancer model was used to evaluate breast cancer progression and metastasis (n = 10/group). Cells were injected into the mammary pad in different ratios and animals were monitored over 42 days. Microdialysis was performed to analyze RANTES levels in the tumor microenvironment (days 21 and 42). Primary and metastatic tumors were weighed and analyzed for oncogene, growth factor, and metastatic marker expression. RESULTS: MDA cell viability increased from 45.5 percent to 95.5 percent in presence of adipose-derived mesenchymal stromal cells in vitro. In vivo, animals with AD-MSC showed increased mean tumor weight (MDA, p < 0.01; MCF versus controls, p < 0.05) and metastatic occurrence (40 percent in MDA; 30 percent in MCF versus 0 percent in controls). Cytokine analysis revealed switching of MCF tumor phenotype to a more malignant type in the presence of adipose-derived mesenchymal stromal cells. CONCLUSION: Human adipose-derived mesenchymal stromal cells may promote progression and metastatic spread in breast cancer through a switch to a more malignant phenotype with worse prognosis. Methods: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-α, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC

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Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps

Cited by 55 publications

References 36 publications

Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

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