Details

Autor(en) / Beteiligte

• Alam, S R
• Lewis, S C
• Zamvar, V
• Pessotto, R
• Dweck, M R
• Krishan, A
• Goodman, K
• Oatey, K
• Harkess, R
• Milne, L
• Thomas, S
• Mills, N M
• Moore, C
• Semple, S
• Wiedow, O
• Stirrat, C
• Mirsadraee, S
• Newby, D E
• Henriksen, P A

Titel

Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial

Ist Teil von

• Heart (British Cardiac Society), 2015-10, Vol.101 (20), p.1639-1645

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2015

Link zum Volltext

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• BackgroundElafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery.Methods and resultsIn a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI −207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI −235 to 711, p=0.320).ConclusionsThere was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury.Trial registration number(EudraCT 2010-019527-58, ISRCTN82061264).