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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Arterioles, Endothelin A Receptor Antagonists, Endothelin B Receptor Antagonists, Graft Survival, Ischemia, Mice, Mice, Inbred C57BL, Microcirculation, Microscopy, Fluorescence, Models, Animal, Necrosis, Oligopeptides, Peptides, Cyclic, Piperidines, Regional Blood Flow, Surgical Flaps, Time Factors, Venules.
user
Does selective blockade of endothelin-B receptor improve survival of critically perfused musculocutaneous flaps? Context: 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. 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). Despite an increase in aBF during the 10-day observation period (day 1 = 1.92 +/- 0.29 nl/s; day 10 = 4.70 +/- 1.64 nl/s), the flaps of saline-treated controls showed a distinct decrease in FCD (94 +/- 12 cm/cm(2)). This perfusion failure resulted in flap necrosis of 52 +/- 3%. Selective blockade of the ET-B receptor caused a further increase in aBF already at day 1 (2.97 +/- 0.42 nl/s), which persisted during the following 10-day observation period (day 10 = 5.74 +/- 0.69 nl/s). Accordingly, adequate FCD could be maintained (day 10 = 215 +/- 8 cm/cm(2); p < 0.05 vs control), resulting in a significant reduction in flap necrosis (day 10 = 25 +/- 4%; p < 0,05). In contrast, neither selective blockade of the ET-A receptor nor nonselective ET-A- and ET-B-receptor blockade were able to significantly affect aBF when compared to controls (day 1 = ET-A = 1.39 +/- 0.10 nl/s; ET-AB = 1.53 +/- 0.80 nl/s; n.s.). Accordingly, flap necrosis after ET-A- and ET-AB-receptor inhibition did not differ from that of controls (day 10 = ET-A: 46 +/- 10%; ET-AB = 51 +/- 7%).
assistant
Our data show that only selective ET-B-receptor inhibition is capable of maintaining nutritive perfusion and, hence, reducing necrosis in critically perfused flap tissue. Accordingly, administration of ET-B-receptor antagonists may be considered in the treatment of critically perfused flaps. Final Decision: yes