MICA: Developmental clinical studies- Effect of elafin on myocardial injury and inflammation in coronary artery bypass surgery

Heart muscle cells are susceptible to injury and death following interruption of blood flow (myocardial ischaemia). A mild form of injury occurs during coronary artery bypass surgey and can be measured using a sensitive blood marker (troponin) providing a helpful model to study drugs that may reduce ischaemic injury. Neutrophils are circulating blood cells that contribute to ischaemic injury by releasing destructive enzymes (elastases). Humans produce a protein called elafin that reduces neutrophil elastase injury. Extensive preclinical work from different international centres indicates that elafin has a therapeutic role in diseases of the arteries and heart characterised by neutrophil mediated injury. We believe that administering elafin to patients undergoing bypass surgery will reduce neutrophil mediated myocardial injury and the rise in post-operative inflammatory activity. The degree of heart muscle damage occurring during ischaemia determines clinical outcomes. No therapies are available to address neutrophil mediated heart muscle injury and development of a drug to reduce this offers substantial clinical benefit.

During coronary artery bypass graft surgery, the myocardium receives an immediate ischaemic insult, exacerbated by post-ischaemic inflammatory responses following reperfusion that lead to increased myocardial injury. Elafin is a potent endogenous anti-elastase with wide ranging anti-inflammatory properties that inhibit destructive post-ischaemic inflammatory pathways. We hypothesise that elafin will reduce peri-operative ischaemic myocardial injury and systemic inflammation in elective coronary artery bypass graft surgery. Myocardial injury will be quantified over the first 48 hours using serial measurements of plasma troponin T concentrations. Subsequent myocardial infarct volume will be quantified by cardiac magnetic resonance imaging. This proof-of-concept study will establish whether elafin has cardioprotective effects in a clinical model of predictable myocardial injury. It has implications for the treatment of ischaemic heart disease, myocardial infarction and other diseases of ischaemic origin.