gms | German Medical Science

132. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

28.04. - 01.05.2015, München

Influence of high levels of Rifampicin on cell viability of vascular cells – impact on successful graft implantation?

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  • Monika Herten - Westfälische Wilhelms-Universität Münster, Klinik für Vaskuläre und Endovaskuläre Chirurgie, Münster, Deutschland

Deutsche Gesellschaft für Chirurgie. 132. Kongress der Deutschen Gesellschaft für Chirurgie. München, 28.04.-01.05.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgch627

doi: 10.3205/15dgch627, urn:nbn:de:0183-15dgch6270

Published: April 24, 2015

© 2015 Herten.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Introduction: Successful graft implantation requires prosthetic vascular graft healing, which is an intricate, interconnected multicellular process culminating in the formation of new tissue. Graft healing involves the coordination of host immune cells activity, migration, infiltration, proliferation and differentiation of endothelial cells (ECs), smooth muscle cells (SMCs) and their progenitors. Negative effect of exogenous factors (i.e. bacterial infection, nutrition deficiencies, stresses) are frequent causes for failures of synthetic grafts by provoking pathological issues such as thrombosis, anastomotic hyperplasia and limited re- endothelisation.

For the restructuring of infected grafts and prevention of graft infections Rifampicin-soaked synthetic prosthetic grafts are clinically used. However in-vitro studies revealed high cytotoxic effects on endothelial cells of concentrated Rifampicin-solution.

The aim of the present study was the investigation of the effect of the antibiotic Rifampicin on vascular endothelial cells (ECs) and smooth muscle cells (SMCs).

Material and methods: Primary human ECs (n=3) and SMC (n=3) of the 2nd and 3rd passage were seeded onto 96-well plates in a cell density of 10.000 cells/cm2. After 24 hours cells were incubated with different concentrations of Rifampicin (n=8 for each concentration and cell type, 384 wells in total) for 24 hr. Subsequently cells were washed and the cell viability determined by measuring the mitochondrial ATP-concentration. Rifampicin concentrations used were the minimum and maximum serum concentration, their decimal multiples and the maximum soaking concentration.

Results: Rifampicin did not influence viability of EC and SMC up to a concentration of the 10-fold maximum serum concentration (100 µg/ml; p>0.170). Higher concentrations (> 1 mg/ml) reduced cell viability of both cell types significantly (p<0.001). High concentrations of Rifampicin (soaking concentration 60 mg/ml) was maximal cytotoxic for EC and SMC (p<0.001).

Conclusion: In randomised clinical studies (with more than 3500 patients) prophylactic pre-soaking of synthetic prosthesis with 1 mg/ml Rifampicin did not show a significant reduction in graft re-infections over the follow up period of 2 years [1]. However numerous reports with more than 150 patients with graft infections show excellent results with presoaking of synthetic graft with high concentrations of Rifampicin (60 mg/ml) [2]. The in-vitro results of the present study display a high cytotoxicity of Rifampicin against vascular cells and may re-initiate the discussion about the advantages of prophylactic pre-soaking with high concentrations of Rifampicin. Further studies are necessary to determine the influence of Rifampicin on the restoration of vessel functionality vs. the preventative character for graft infections.


References

1.
Earnshaw JJ. The current role of rifampicin-impregnated grafts: pragmatism versus science. Eur J Vasc Endovasc Surg. 2000 Nov;20(5):409-12.
2.
Lew W, Moore W. Antibiotic-impregnated grafts for aortic reconstruction. Semin Vasc Surg. 2011 Dec;24(4):211-9. DOI: 10.1053/j.semvascsurg.2011.10.015 External link