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This is a prospective, single-centre case control comparison of expression of target genes responsible for energy utilisation, mitochondrial function and oxidative stress and levels of histone acetylation/ DNA methylation in obese and non-obese adult cardiac surgery patients. The study aims to test several inter-related hypotheses in a consecutive sequence of patients undergoing coronary artery bypass grafting.
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| Measure | Description | Time Frame |
|---|---|---|
| Post surgery inotrope score | inotrope score measured up to 48 hours post-surgery | inotrope score measured up to 48 hours post-surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in expression of target genes | from right atrial biopsies | Collected at the time of surgery |
| Changes in epigenetic regulation of target genes from left atrial biopsies. | histone acetylation, DNA methylation |
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Inclusion Criteria:
Exclusion Criteria:
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The study will be carried out at a large tertiary academic cardiac surgery unit in the UK; the University Hospitals of Leicester NHS Trust. This unit performs over 1,200 major cardiac procedures per year, of which 600 are patients undergoing coronary artery bypass grafting
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tracy Kumar | Contact | 01162583039 | tk98@leicester.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Gavin Murphy | University of Leicester | Principal Investigator |
| Filiberto Serraino | University of Leicester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| England | Recruiting | Glenfield | Leicestershire | LE3 9QP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22797452 | Background | ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. | |
| 7587228 | Background | Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995 Oct;23(10):1638-52. doi: 10.1097/00003246-199510000-00007. |
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Atrial Biopsy: A 0.5cm x 0.5cm section of the right atrial wall is routinely excised to allow cannulation of the left atrium for connection to the cardiopulmonary bypass machine. This segment is routinely discarded. We propose to collect this specimen immediately after it has been discarded.
| Collected at the time of surgery |
| Changes in mitochondrial function | in atrial biopsies and buffy coats of blood samples collected before and after surgery | before and after sugery (up to 12 hours post surgery) |
| Myocardial Injury | defined by post cardiac surgery serum Troponin levels | baseline and 24 hours |
| Acute kidney injury | defined by serum creatinine level postoperatively, as per the KDIGO criteria | baseline, and up to 15 days post surgery (discharge) |
| Perioperative clinical characteristics | Perioperative clinical characteristics | Collected pre op |
| Perioperative medications. | Perioperative medications. | Collected pre op |
| Data to calculate Multiple Organ Dysfunction (MOD) score. | To calculate the MOD score, the Respiratory Function (calculated as partial pressure of oxygen (PaO2) divided by fraction of inspired oxygen (FiO2)), Cardiovascular (Pressure adjusted heart rate (PAR) ), Renal (Serum Creatinine), Hepatic (serum bilirubi | baseline, and up to 96 hours post surgery |
| Data to capture Acute Respiratory Distress Syndrome (Berlin criteria ARDS). | Acute Lung Injury (ALI) non-ARDS, ARDS. To define these different categories of acute lung injury, the Positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) will be recorded in the CRF at time points: Pre-OP, ICU, 12 hrs post-op,24hrs post-op,48hrs post-op,72hrs post-op and 96hrs post-op. Along with the PaO2/FiO2 ratio, it will then be possible to categorise patients into the above definitions of acute lung injury as follows: ALI non-ARDS (200 mmHg <PaO2/FiO2<300 mmHg, regardless of PEEP),ARDS (PaO2/FiO2<200 mmHg, regardless of PEEP), mild Berlin Definition(200mmHg <PaO2/FiO2<300mmHg with PEEP > 5cm H2O),moderate Berlin Definition(100mmHg <calculated as partial pressure of oxygen divided by fraction of inspired oxygen PaO2/FiO2 < 200mmHg with PEEP > 5cm H2O) and Severe Berlin Definition (PaO2/FiO2 < 100mmHg with PEEP > 5cm H2O) | baseline, and up to 96 hours post surgery |
| Data on demographics | Height in cms | Pre Op |
| Data on demographics | Weight in kgs | Pre Op |
| 35082386 | Derived | Adebayo AS, Roman M, Zakkar M, Yusoff S, Gulston M, Joel-David L, Anthony B, Lai FY, Murgia A, Eagle-Hemming B, Sheikh S, Kumar T, Aujla H, Dott W, Griffin JL, Murphy GJ, Wozniak MJ. Gene and metabolite expression dependence on body mass index in human myocardium. Sci Rep. 2022 Jan 26;12(1):1425. doi: 10.1038/s41598-022-05562-8. |