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Preoperative High Intensity Interval Training: The PHIIT Trial

ABSTRACT: Colorectal and thoracic surgical patients are susceptible to poor postoperative outcome including complications, mortality and increased length of stay. Preoperative physical fitness is protective against poor postoperative outcome in intra-abdominal and thoracic surgery. The current colorectal/thoracic pathway from diagnosis to surgery is about 2 weeks and therefore interventions of longer duration are not feasible. Clinicians may be presented with a difficult choice in delaying surgery to perform prehab or cancel the pre-op intervention. To create greater improvements in aerobic fitness, participants are required to exercise at high levels of VO2peak (e.g. ≥80% VO2peak). High intensity interval training (HIIT) requires participants to exercise at high levels of VO2peak (≥80% VO2peak) for short periods (e.g. 15 seconds) followed by a recovery (active or passive) and typically continue this pattern for 30 minutes or until exhaustion. HIIT programmes are safe and a recent meta-analysis noted that HIIT produced a more pronounced incremental gain in participants’ mean VO2peak when compared with continuous moderate intensity exercise (+1.78mL/kg/min, 95% CI: 0.45-3.11). HITT has not been investigated as a preoperative intervention to either optimize fitness prior to surgery or reduce post-surgical complications. Preoperative HIIT is an intense intervention which will require significant participant adherence. The safety, cost and clinical application of such a programme needs to be performed. This feasibility study aims to assess the ability of HIIT to improve aerobic fitness two weeks prior to surgery and determine its feasibility.

DISEASE(S): Colorectal Neoplasms,Lung Neoplasms,Neoplasms

PROVIDER: 2207678 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in 5 male sport team members using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 minutes and 24 hours post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed x distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 mins and 24 hrs post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 minutes post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via change of direction exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.

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Preoperative High Intensity Interval Training: The PHIIT Trial

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