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).
The technique of early extubation after coronary artery bypass grafting is increasing in popularity, but its safety and effect on myocardial ischaemia remain to be established. In a randomized, prospective study, patients undergoing routine elective coronary artery bypass grafting were managed with either early or late tracheal extubation. The incidence and severity of electrocardiographic myocardial ischaemia were compared. Data were analysed from 85 patients (43 early extubation; 42 late extubation). Median time to extubation was 110 min in the early extubation patients and 757 min in the late extubation patients. After correction for randomization bias, there were no significant differences between groups in ischaemic burden, maximal ST-segment deviation, incidence of ischaemia and area under the ST deviation-time curve (integral of ST deviation and time). Similarly, there were no differences between groups in postoperative creatine kinase MB-isoenzyme concentrations and duration of stay in the ICU or hospital. Therefore, this study provides evidence for the safety of early extubation after routine coronary artery bypass grafting.
The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.
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