N-acetylcysteine attenuates leukocytic inflammation and microvascular perfusion failure in critically ischemic random pattern flaps

IntroductionMicrocirculatory dysfunction causes ischemia resulting in tissue necrosis. N-acetylcysteine (NAC) has been shown capable of protecting tissue from ischemic necrosis. However, the mechanism of action of NAC is yet not fully understood.ObjectiveHerein, we studied whether NAC is capable of attenuating microvascular perfusion failure in critically ischemic musculo-cutaneous tissue.Material and methodsA laterally based skin flap was elevated in the dorsum of C57BL/6 mice and fixed into a dorsal skinfold chamber. Arteriolar perfusion, functional capillary density, leukocytic inflammation, apoptotic cell death, and non-perfused tissue area were repetitively analyzed over 10 days by intravital fluorescence microscopy. Treatment with either 100 mg/kg NAC or saline (control) was started 30 min before surgery and was continued until day 10 after flap elevation.ResultsSurgery induced leukocytic inflammation, microvascular perfusion failure, apoptosis, and tissue perfusion failure. NAC was capable of significantly attenuating the area of non-perfused tissue. This was associated by a marked arteriolar dilation and an increased capillary perfusion. NAC further reduced the ischemia-associated leukocytic response and significantly attenuated apoptotic cell death in all areas of the flap.ConclusionNAC is effective to attenuate leukocytic inflammation and microvascular perfusion failure in critically ischemic tissue. Thus, NAC treatment may represent a promising approach to improve the outcome of ischemically endangered flap tissue.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► N-acetylcysteine (NAC) maintains nutritive perfusion in critically perfused flaps. ► NAC reduces inflammation and apoptotic cell death in critically perfused flaps. ► NAC significantly reduces necrosis in ischemically endangered flap tissue.