Technische Universität München Fakultät für Medizin Klinikum rechts der Isar Klinik und Poliklinik für Plastische Chirurgie und Handchirurgie (Direktor: Prof. Dr. Hans-Günther Machens) Superficial Burns & Secondary Burn-Injury Progression: A Rat Model for Topical Application of Tissue Protective Agents Fabian Dominik Weiß Vollständiger Abdruck der von der Fakultät für Medizin der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Medizinischen Wissenschaften (Dr. med. sci.) genehmigten Dissertation. Vorsitzender: apl. Prof. Dr. Klaus-Peter Janssen Prüfer der Dissertation: 1. apl. Prof. Dr. Yves Harder 2. Priv.-Doz. Dr. Alexander Konstantinow Die Dissertation wurde am 05.03.2020 bei der Technischen Universität München eingereicht und durch die Fakultät für Medizin am 07.10.2020 angenommen. für meine Eltern I II 1 Contents 1 Contents ..................................................................................................................................................... III 2 Figure Legends ........................................................................................................................................ IV 3 Table Legends ............................................................................................................................................ V 4 Overview of Abbreviations ................................................................................................................ VI 5 Summary ................................................................................................................................................... VII 5.1 English Abstract ........................................................................................................................................... VII 5.2 Deutsche Zusammenfassung .................................................................................................................... IX 6 Introduction ................................................................................................................................................ 1 6.1 Overview ............................................................................................................................................................. 1 6.2 Burn Injury Definition ................................................................................................................................... 1 6.3 Burn Depth ......................................................................................................................................................... 2 6.4 Burn Extent: Affected Total Body Surface Area .................................................................................. 6 6.5 Secondary Burn Wound Progression ...................................................................................................... 8 6.6 Experimental Approaches to Burn Wound Progression ............................................................. 13 6.7 Tissue Protective Agents to Reduce Burn Wound Progression ............................................... 17 6.8 Laser-Speckle-Contrast: Technique and Imaging ........................................................................... 19 7 Purpose of this Study ........................................................................................................................... 22 8 Material & Methods .............................................................................................................................. 23 8.1 Animals & Housing ....................................................................................................................................... 23 8.2 Preparation For Burn Induction ............................................................................................................ 23 8.3 Burn Induction ............................................................................................................................................... 24 8.4 Measurements: Digital Photo Documentation and Perfusion-Flowmetry .......................... 26 8.5 Frame Dressing .............................................................................................................................................. 28 8.6 Euthanasia, Histology and Burn Depth Score ................................................................................... 34 8.7 Evaluation of Macroscopic Interspace Necrosis ............................................................................. 36 8.8 LSCI Flowmetry Data Processing ........................................................................................................... 36 8.9 Statistical Analysis ....................................................................................................................................... 39 9 Results ........................................................................................................................................................ 40 9.1 Histological Burn Depth ............................................................................................................................. 40 9.2 Macroscopic Interspace Necrosis .......................................................................................................... 43 9.3 Microcirculatory Perfusion ...................................................................................................................... 46 9.4 Frame Quality ................................................................................................................................................. 57 10 Discussion .............................................................................................................................................. 63 10.1 Burn Depth .................................................................................................................................................... 63 10.2 Macroscopic Interspace Necrosis ....................................................................................................... 69 10.3 Perfusion Parameters .............................................................................................................................. 74 10.4 Frame Evaluation ....................................................................................................................................... 84 10.5 Further Research ....................................................................................................................................... 89 11 Conclusion ............................................................................................................................................. 92 12 Bibliography ......................................................................................................................................... 93 13 Acknowledgements ......................................................................................................................... 106 14 Attachments ........................................................................................................................................ 108 III 2 Figure Legends Figure 1: Wallace Rule of Nines .................................................................................................................................. 7 Figure 2: Lund-Browder Chart ................................................................................................................................... 8 Figure 3: Jackson Burn Wound Model ..................................................................................................................... 9 Figure 4: Pathways of Secondary Burn Wound Progression ...................................................................... 12 Figure 5: Schematic Laser-Speckle Contrast-Imaging ................................................................................... 20 Figure 6: Stamp Position Outlining ........................................................................................................................ 24 Figure 7: Burn Comb Template ............................................................................................................................... 25 Figure 8: Rat Dorsum after Burn Induction ....................................................................................................... 25 Figure 9: Measurement Points ................................................................................................................................. 26 Figure 10: Example of Photo Documentation ................................................................................................... 27 Figure 11: Example of LSCI Measurement .......................................................................................................... 28 Figure 12: First Preliminary Frame ....................................................................................................................... 29 Figure 13: Second Preliminary Frame with Thermoplastic Material ..................................................... 30 Figure 14: Single Layer Aluminium Frame ......................................................................................................... 30 Figure 15: Assembled Final Aluminium Frame ................................................................................................ 31 Figure 16: Mounted Double-Layered Aluminium Frame ............................................................................