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

Wettstein, Reto; Mörsdorf, P.; Bächle, Annick; Amon, M.; Pittet, Brigitte; Menger, Michael D.; Harder, Yves

doi:10.1007/s00423-007-0163-8

Cited by 4 publications

(3 citation statements)

References 28 publications

(37 reference statements)

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“…33 Wettstein et al showed that the administration of ET-B receptor antagonists is useful in the treatment of critically perfused flaps. 34 This study shows parallel results with the aforementioned studies. Bosentan, both ETA and ETB receptor antagonists, increased flap survival.…”

Section: Discussionsupporting

confidence: 88%

Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on Flap Survival in Rats: An Experimental Study

et al. 2016

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Local skin flaps are important tools for performing plastic surgery. Skin flaps are used for closure of defects after tumor excision or in tissue losses after trauma. However, problems associated with these flaps are commonly encountered, particularly in areas of marginal necrosis. Bosentan is a vasodilator that exerts its effect through endothelin receptor blockade, and has been shown to prevent ischemic tissue damage. However, no reports have addressed the effect of bosentan on skin flaps. The aim of the study was to investigate the effects of bosentan, which may be applied clinically to promote survival of ischemic skin flaps. A modified McFarlane flap was elevated in the dorsum of 20 Albino Wistar rats with a width-to-length ratio of 3 to 10 cm, respectively, with the caudal base. Perioperatively, 0.9% of physiologic NaCl and injectable distilled water of identical volume were injected into rats in Group 1 (n = 10), and 5 mg/kg bosentan was injected intraperitoneally into rats in Group 2 (n = 10). All of the rats were followed up for 7 days postoperatively. The surviving parts of the flaps were measured at the end of day 7. Acute and chronic inflammation, amount of granulation tissue, fibroblast maturation, amount of collagen, and amounts of reepithelialization and neovascularization present in the ischemic zones of the distal parts of the flaps were evaluated histopathologically, and results were compared statistically. The mean flap survivals were 61.1% in Group 1 and 91.1% in Group 2; the percentage of the surviving flap area in Group 2 was higher than that in Group 1 (p < 0.005). In both groups, there was significantly less acute inflammation in the ischemic zones in Group 2 than in Group 1 (p < 0.005). No significant difference was found in the amounts of chronic inflammation and granulation tissue between the two groups (p > 0.005). Fibroblast maturation, amount of collagen, and amounts of reepithelialization and neovascularization investigated in Group 2 were statistically significantly higher than those in Group 1 (p < 0.005). We believe that bosentan may be used prophylactically to increase survival in risky skin flaps because it decreases ischemic necrosis distal to skin flaps, thus exerting favorable effects on flap survival.

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Section: Discussionsupporting

confidence: 88%

Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on Flap Survival in Rats: An Experimental Study

et al. 2016

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“…The doses were selected on the basis of studies from our laboratory and other laboratories that showed them to be effective in vivo and in vitro. 10,11,45,46 Treatment or placebo was maintained for 4 additional weeks, BP was continuously monitored by telemetry, and at 10 weeks, MDCT in vivo studies were repeated as done at 6 weeks. The remaining five animals with RVD did not receive any additional treatments and served as untreated controls.…”

Section: Concise Methodsmentioning

confidence: 99%

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

Chade¹,

Tullos²,

Stewart³

et al. 2015

Journal of the American Society of Nephrology

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Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. Chronic renovascular disease (RVD) increases the risk of cardiovascular morbidity and mortality and may progressively induce renal injury, leading to ESRD. 1 Percutaneous transluminal renal angioplasty/stenting (PTRAS) is a frequently used therapeutic strategy to treat patients with chronic RVD. Targeting the renal stenosis is a logical choice for treating RVD, because the resolution of the vascular obstruction followed by restoration of blood flow to the site of injured tissues should play an important role to initiate successful repairing responses. The use of PTRAS in RVD grew significantly during the past 20 years, 2 with tremendous progress in successfully resolving renal stenosis and restoring blood flow (.95% of the cases). 3 However, despite the high technical success of PTRAS, improvement in renal function is still observed in a relatively small portion of the cases. 4 The reasons for the persistent poor outcomes after PTRAS in RVD are still unclear. Furthermore, the dissociation between the technical success of PTRAS and renal outcomes underscores a pressing need to identify more effective therapeutic strategies in RVD.Endothelin-1 (ET-1) is a powerful renal vasoconstrictor and mitogenic peptide that plays important roles in controlling BP and renal function.

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“…Additional studies have shown that the perfusion and survival of the flap can be improved by different therapeutic approaches. These include local heat preconditioning (Harder et al, 2005b), selective blockade of endothelin-B receptor (Wettstein et al, 2007) as well as pharmacological treatment with EPO (Rezaeian et al, 2008;Harder et al, 2009;Rezaeian et al, 2013), n-acetylcysteine (Bächle et al, 2011) and ghrelin (Rezaeian et al, 2012). Promising results of these preclinical studies have encouraged the conduction of first translational studies in the clinical setting.…”

Section: Mw Laschke and MD Mengermentioning

confidence: 99%

The dorsal skinfold chamber: A versatile tool for preclinical research in tissue engineering and regenerative medicine

Laschke

Menger²

2016

eCM

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The dorsal skinfold chamber is a rodent model for non-invasive microcirculatory analyses of striated muscle and skin tissue throughout an observation period of 2-3 weeks. In combination with intravital fluorescence microscopy, this model allows the quantitative assessment of dynamic processes such as inflammation, angiogenesis, vascular remodelling and microcirculation. Accordingly, the dorsal skinfold chamber is increasingly used for preclinical research in tissue engineering and regenerative medicine. This includes studies on biocompatibility, vascularisation and incorporation of medical implants and artificial tissue constructs. Moreover, the chamber implantation procedure has been modified to analyse primary and secondary wound healing as well as revascularisation and blood perfusion of dermal substitutes, skin grafts and myocutaneous flaps. Hence, the dorsal skinfold chamber model does not only provide deep insights into fundamental regenerative mechanisms but also represents a versatile tool for the development of novel therapeutic strategies.

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

Cited by 4 publications

References 28 publications

Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on Flap Survival in Rats: An Experimental Study

Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on Flap Survival in Rats: An Experimental Study

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

The dorsal skinfold chamber: A versatile tool for preclinical research in tissue engineering and regenerative medicine

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