Transcriptional responses in the adaptation to ischaemia-reperfusion injury: a study of the effect of ischaemic preconditioning in total knee arthroplasty patients | Murphy et al. Journal of Translational Medicine 2010 8 46 http content 8 1 46 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Transcriptional responses in the adaptation to ischaemia-reperfusion injury a study of the effect of ischaemic preconditioning in total knee arthroplasty patients Terence Murphy21 2 Pauline M Walsh21 Peter P Doran 1 2 and Kevin J Mulhall 1 2 Abstract Background Ischaemic preconditioning IPC has emerged as a method of reducing ischaemia-reperfusion injury. However the complex mechanism through which IPC elicits this protection is not fully understood. The aim of this study was to investigate the genomic response induced by IPC in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the IPC mechanism. Methods Twenty patients undergoing primary total knee arthroplasty were randomly assigned to IPC n 10 and control n 10 groups. Patients in the IPC group received ischaemic preconditioning immediately prior to surgery. IPC was induced by three five-minute cycles of tourniquet insufflation interrupted by five-minute cycles of reperfusion. A muscle biopsy was taken from the operative knee of control and IPC-treated patients at the onset of surgery and again at one hour into surgery. The gene expression profile of muscle biopsies was determined using the Affymetrix Human U113 microarray system and validated using real-time polymerase chain reaction RT-PCR . Measurements of C-reactive protein CRP erythrocyte sedimentation ESR white cell count WCC cytokines and haemoglobin were also made pre- and post-operatively. Results Microarray analysis revealed a significant increase in the expression of important oxidative stress defence genes immediate early response genes and mitochondrial genes. Upregulation of pro-survival genes was also observed and correlated with a downregulation of pro-apoptotic gene expression. CRP ESR WCC cytokine and haemoglobin levels
