35060 The Impact of N-Acetylcysteine on Autologous Fat Graft - First-in-Human Pilot Study

Monday, October 1, 2018: 8:15 AM
Piotr Pietruski, MD, PhD , Department of Plastic Surgery, Centre of Postgraduate Medical Education, Warsaw, Poland
Wiktor Paskal, MD , Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
Adriana Paskal, MD , Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
Lukasz Paluch, MD, PhD , Department of Radiology, Centre of Postgraduate Medical Education, Otwock, Poland
Pawel Wlodarski, MD, PhD , Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
Jerzy Walecki, MD, PhD , Department of Radiology, Centre of Postgraduate Medical Education, Otwock, Poland
Bartlomiej H Noszczyk, MD , Department of Plastic Surgery, Medical Centre of Postgraduate Education, Warsaw, Poland

The aim of this pilot study was to determine whether N-acetylcysteine (NAC) administered at the fat graft donor site during the harvest procedure reduces oxidative stress and thus, improves graft survivability.

The study included 15 women with mean age of 31.8 years (range, 23-39 years). A 200-ml adipose tissue graft was harvested from each thigh in each study subject. The procedure of graft harvesting from one thigh, considered as the control (n=15), included infiltration with a standard tumescent fluid. During harvesting the graft from the other thigh, a tumescent fluid containing NAC (Sandoz, Holzkirchen, Germany) was used (NAC group, n=15). Plastic surgeon who conducted the procedure was blinded to the type of administered fluid. All patients were followed-up for 6-months for potential adverse events associated with administration of the modified tumescent fluid. A 65-ml adipose tissue sample from each graft was subjected to immediate and postponed biochemical analysis, flow cytometric assay and Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). The rest of the graft was used for correction of breast asymmetry, to determine the degree of fat resorption based on the comparison of pre- and postoperative MRI findings (separate study).

During biochemical tests, the severity of oxidative stress was determined based on the levels of reactive oxygen species (ROS) and nitric oxide (NO), along with the concentration and activity of superoxide dismutase (SOD). qRT-PCR analysis included targets linked with oxidative stress (GPX-3, hsCAT, hsSOD, iNOS, HO-1), angiogenesis (VEGF, ANG-2) and adipogenesis (PPAR-γ, C/EBP β).

Normal distribution of the study variables was verified with Kolmogorov-Smirnov test. Intragroup comparisons were carried out with Wilcoxon signed-rank test. All calculations were conducted with Statistica 10 (StatSoft, Tulsa, OK, USA), with the threshold of statistical significance set at p<0.05.

Neither local nor systemic postoperative complications were observed in the study subjects during a 6-month follow-up. Concentration of SOD in the NAC group turned out to be significantly higher than in the controls, in both fresh (p=0.041) and frozen samples (p=0.004). Also SOD activity in NAC group was significantly higher, both in fresh and frozen samples (p=0.023 and p=0.003, respectively). Interestingly, no statistically significant intergroup differences were observed in terms of ROS levels. The level of NO in frozen samples from the controls was significantly higher than in NAC group (p=0.009). The only qRT-PCR target showing significant intergroup differences was iNOS (encoding inducible NO synthase), with higher transcription levels observed in the controls (p=0.027).

The results of this study imply that addition of NAC to tumescent solution may counteract oxidative stress the cells of autologous fat graft are exposed to during the harvesting procedure. This may contribute to lesser volume of the graft that undergoes resorption over time (the study is still ongoing). The lack of adverse events after the infiltration of the fat graft donor site with NAC-enriched solution suggests that this technique is safe. If addition of NAC was shown to improve the retention of the graft, this technique might become a routine adjunct method used during this type of procedures.