Evolution of ischemic tissue injury in a random pattern flap: A new mouse model using intravital microscopy

Harder, Yves; Amon, M.; Erni, Dominique; Menger, Michael D.

doi:10.1016/j.jss.2004.03.026

Cited by 58 publications

(45 citation statements)

References 51 publications

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“…Ischemia in musculocutaneous tissue was induced by the creation of a random pattern flap. The inclusion of the flap into the dorsal skinfold chamber results in necrosis of ∼50% of the distal tissue as previously described in detail [18]. Briefly, after depilation of the back of the animal, a random pattern flap including skin and panniculus carnosus was elevated perpendicular to the spine.…”

Section: Methodsmentioning

confidence: 99%

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Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps

Wettstein

Mörsdorf

Bächle

et al. 2007

Langenbecks Arch Surg

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Background and aims Insufficient perfusion of distal flap areas, which may lead to partial necrosis, still represents a challenge in reconstructive surgery. In the process of microvascular and endothelial dysfunction, endothelins (ETs) and their receptors may play an important role. Therefore, the aim of the study was to investigate in a chronic in vivo model the effect of various ET-receptor antagonists in critically perfused flap tissue. Materials and methods A random pattern musculocutaneous flap was elevated in the back of 25 C57BL/6 mice and fixed into a dorsal skinfold chamber. Repetitive intravital fluorescence microscopy was performed over a 10-day observation period, assessing arteriolar diameter, arteriolar blood flow (aBF), functional capillary density (FCD), the area of tissue necrosis, and the development of newly formed blood vessels. ET-receptor blockers were administrated intraperitoneally 30 min before induction of ischemia, as well as daily during the subsequent 4-day period, including (1) BQ-123, a specific ET-A-receptor antagonist (ET-A=1 mg/kg), (2) BQ-788, a selective ET-B-receptor antagonist (ET-B=1 mg/kg), and (3) PD-142893, a nonselective ET-AB-receptor antagonist (ET-AB=0.5 mg/kg). Animals receiving saline only served as controls (n=7).Results Despite an increase in aBF during the 10-day observation period (day 1=1.92±0.29 nl/s; day 10=4.70±

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Section: Methodsmentioning

confidence: 99%

“…To this end, we used the previously modified dorsal skinfold chamber that includes a random pattern musculocutaneous flap, which develops a 50% necrosis if untreated [18].…”

Section: Introductionmentioning

confidence: 99%

Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps

Wettstein

Mörsdorf

Bächle

et al. 2007

Langenbecks Arch Surg

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“…20 As previously described, the musculocutaneous tissue is subjected to persistent ischemia resulting in B50% necrosis if kept untreated. 21 The preparation starts after depilation by mobilization of the musculocutaneous tissue (that is, induction of ischemia). The rectangular flap of 15 Â 11 mm remains attached to the animal only on its lateral border.…”

Section: Flap Preparationmentioning

confidence: 99%

Erythropoietin-induced upregulation of endothelial nitric oxide synthase but not vascular endothelial growth factor prevents musculocutaneous tissue from ischemic damage

Rezaeian

Wettstein

Egger

et al. 2010

Laboratory Investigation

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Recent findings have attested the protective effects of erythropoietin (EPO) in ischemically challenged organs. We therefore aimed at elaborating the underlying mechanism of EPO-mediated protection in musculocutaneous tissue undergoing persistent ischemia after acute injury. Mice were assigned to five experimental groups equipped with a randomly perfused flap fixed in a dorsal skinfold chamber, whereas the sixth group did not undergo flap preparation: EPO, L-Name, EPO and L-Name, EPO and bevacizumab, untreated flap, and nonischemic chamber (control). Intravital fluorescence microscopic analysis of microhemodynamics, apoptotic cell death, macromolecular leakage and angiogenesis was carried out over a 10-day period. Further, immunohistochemical analysis was used to study the protein expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). Increased expression of eNOS in EPO-administered mice correlated with significant arteriolar dilation and thus increased blood flow resulting in a maintained functional capillary density (FCD) at day 10. In addition, EPO induced a VEGF upregulation, which was associated with newly formed capillaries. In addition, EPO was able to reduce ischemia-induced apoptotic cell death and finally to significantly reduce flap necrosis. In contrast, coadministration of L-Name abolished EPO-mediated tissue protection by abrogating the dilatory effect resulting in reduced FCD and tissue survival, without counteracting angiogenesis and apoptotic cell death, whereas additional administration of bevacizumab did not influence the beneficial effect of EPO on flap survival despite abrogating angiogenesis. Macromolecular leakage was found to be increased in all treatment groups. This study shows that EPO administration prevents musculocutaneous tissue from ischemic necrosis as a consequence of an eNOS-dependent arteriolar hyperperfusion maintaining capillary perfusion, thus representing a promising approach to pharmacologically protect ischemically challenged tissue.

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“…In the literature, there are controversial reports about the timing of angiogenesis after flap surgery or wound healing. Some of the studies claim an increase in angiogenesis after the first week [39,40] while others report an onset as early as the second day. [11,38] Our findings advocate an early onset of angiogenesis since the increase in the number of capillaries was already evident on the seventh day.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Effects of Losartan on Random Pattern Skin Flap Model of Rats

Öztürk¹,

Tezel²,

Yalçın³

2011

Ulus Travma Acil Cerrahi Derg

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AMAÇLosartanın enflamasyonu baskılayarak çeşitli organlarda iskemi-reperfüzyon hasarını azalttığı ve enfarkt alanını kü-çülttüğü ortaya konmuştur. Bu çalışma, losartanın deri fleplerindeki iskemik bölgeye ve flep sürvisine etkisini ortaya koymak amacıyla planlandı. GEREÇ VE YÖNTEMSprague-Dawley sıçanlarda (n=24) 3x9 cm boyutlarında kaudal pediküllü sırt flebi kaldırıldı. Sıçanlar 3 gruba ayrıla-rak 1. gruba 10 mg/kg, 2. gruba 40 mg/kg losartan ve 3. gruba distile su verildi. Yedi günlük tedavinin sonunda fleplerdeki canlı doku alanı hesaplanarak gruplar arasında karşılaş-tırıldı. Ek olarak fleplerin proksimal ve iskemik bölgelerinde nötrofiller, fibroblastlar, mast hücreleri ve kapillerler sayıldı. BULGULARFleplerdeki canlı doku alanları ortalaması 1., 2. ve 3. gruplarda sırasıyla %61, %56 ve %60 olarak hesaplandı. Gruplar flep sağkalımı açısından karşılaştırıldığında anlamlı fark bulunmadı (p>0,05). Tüm gruplarda fleplerin iskemik bölgesinde nötrofil, fibroblast ve kapillerlerde anlamlı artış saptanırken (p<0,05), mast hücre sayısında fark bulunmadı. 40 mg/kg losartan ile tedavi alan grupta fleplerin yaşayan bölgesinde fibroblast sayısı anlamlı olarak azaldı (p<0,05). Nötrofil, mast hücreleri ve kapiller sayıları ise tedaviden etkilenmedi. SONUÇLosartan sıçan sırt deri flebinin sürvisini arttırmamakta ancak fibroblastlar üzerine anlamlı antiproliferatif etkisi bulunmaktadır.Anahtar Sözcükler: Anjiyotensin; AT1; flep sürvisi, fibroblast; iskemik flep; iskemi reperfüzyon; losartan; reperfüzyon hasarı.

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Evolution of ischemic tissue injury in a random pattern flap: A new mouse model using intravital microscopy

Cited by 58 publications

References 51 publications

Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps

Selective blockade of endothelin-B receptor improves survival of critically perfused musculocutaneous flaps

Erythropoietin-induced upregulation of endothelial nitric oxide synthase but not vascular endothelial growth factor prevents musculocutaneous tissue from ischemic damage

Evaluation of Effects of Losartan on Random Pattern Skin Flap Model of Rats

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