Wendy E Heywood1, Emily Bliss1, Fatima Bahelil2, Trinda Cyrus2, Marilena Crescente3, Timothy Jones2, Sadaf Iqbal4, Laura G Paredes4, Andrew J Toner5, Ana G Del Arroyo2, Edel A O'Toole6, Kevin Mills1, Gareth L Ackland7. 1. Translational Mass Spectrometry Research Group, UCL Institute of Child Health, London, UK. 2. Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. 3. Department of Life Sciences, Manchester Metropolitan University Manchester, UK. 4. University College London NHS Hospitals Trust, London, UK. 5. Department of Anesthesia, Royal Perth Hospital, Perth, Western Australia, Australia. 6. Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK. 7. Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address: g.ackland@qmul.ac.uk.
Abstract
BACKGROUND: Maintaining adequate oxygen delivery (DO2) after major surgery is associated with minimising organ dysfunction. Skin is particularly vulnerable to reduced DO2. We tested the hypothesis that reduced perioperative DO2 fuels inflammation in metabolically compromised skin after major surgery. METHODS: Participants undergoing elective oesophagectomy were randomised immediately after surgery to standard of care or haemodynamic therapy to achieve their individualised preoperative DO2. Abdominal punch skin biopsies were snap-frozen before and 48 h after surgery. On-line two-dimensional liquid chromatography and ultra-high-definition label-free mass spectrometry was used to characterise the skin proteome. The primary outcome was proteomic changes compared between normal (≥preoperative value before induction of anaesthesia) and low DO2 (<preoperative value before induction of anaesthesia) after surgery. Secondary outcomes were functional enrichment analysis of up/down-regulated proteins (Ingenuity pathway analysis; STRING Protein-Protein Interaction Networks). Immunohistochemistry and immunoblotting confirmed selected proteomic findings in skin biopsies obtained from patients after hepatic resection. RESULTS: Paired punch skin biopsies were obtained from 35 participants (mean age: 68 yr; 31% female), of whom 17 underwent oesophagectomy. There were 14/2096 proteins associated with normal (n=10) vs low (n=7) DO2 after oesophagectomy. Failure to maintain preoperative DO2 was associated with upregulation of proteins counteracting oxidative stress. Normal DO2 after surgery was associated with pathways involving leucocyte recruitment and upregulation of an antimicrobial peptidoglycan recognition protein. Immunohistochemistry (n=6 patients) and immunoblots after liver resection (n=12 patients) supported the proteomic findings. CONCLUSIONS: Proteomic profiles in serial skin biopsies identified organ-protective mechanisms associated with normal DO2 after major surgery. CLINICAL TRIAL REGISTRATION: ISRCTN76894700.
BACKGROUND: Maintaining adequate oxygen delivery (DO2) after major surgery is associated with minimising organ dysfunction. Skin is particularly vulnerable to reduced DO2. We tested the hypothesis that reduced perioperative DO2 fuels inflammation in metabolically compromised skin after major surgery. METHODS: Participants undergoing elective oesophagectomy were randomised immediately after surgery to standard of care or haemodynamic therapy to achieve their individualised preoperative DO2. Abdominal punch skin biopsies were snap-frozen before and 48 h after surgery. On-line two-dimensional liquid chromatography and ultra-high-definition label-free mass spectrometry was used to characterise the skin proteome. The primary outcome was proteomic changes compared between normal (≥preoperative value before induction of anaesthesia) and low DO2 (<preoperative value before induction of anaesthesia) after surgery. Secondary outcomes were functional enrichment analysis of up/down-regulated proteins (Ingenuity pathway analysis; STRING Protein-Protein Interaction Networks). Immunohistochemistry and immunoblotting confirmed selected proteomic findings in skin biopsies obtained from patients after hepatic resection. RESULTS: Paired punch skin biopsies were obtained from 35 participants (mean age: 68 yr; 31% female), of whom 17 underwent oesophagectomy. There were 14/2096 proteins associated with normal (n=10) vs low (n=7) DO2 after oesophagectomy. Failure to maintain preoperative DO2 was associated with upregulation of proteins counteracting oxidative stress. Normal DO2 after surgery was associated with pathways involving leucocyte recruitment and upregulation of an antimicrobial peptidoglycan recognition protein. Immunohistochemistry (n=6 patients) and immunoblots after liver resection (n=12 patients) supported the proteomic findings. CONCLUSIONS: Proteomic profiles in serial skin biopsies identified organ-protective mechanisms associated with normal DO2 after major surgery. CLINICAL TRIAL REGISTRATION: ISRCTN76894700.
Authors: Rupert M Pearse; David A Harrison; Neil MacDonald; Michael A Gillies; Mark Blunt; Gareth Ackland; Michael P W Grocott; Aoife Ahern; Kathryn Griggs; Rachael Scott; Charles Hinds; Kathryn Rowan Journal: JAMA Date: 2014-06-04 Impact factor: 56.272
Authors: Damian Szklarczyk; Annika L Gable; David Lyon; Alexander Junge; Stefan Wyder; Jaime Huerta-Cepas; Milan Simonovic; Nadezhda T Doncheva; John H Morris; Peer Bork; Lars J Jensen; Christian von Mering Journal: Nucleic Acids Res Date: 2019-01-08 Impact factor: 16.971