Ischemic Conditioning in STEMI Patients

Myocardial infarction is a common, morbid and mortal disease. This study will examine both the clinical effects of the treatment as well as the molecular mechanism. Evaluating patients in the emergency department (ED) is more than a daily occurrence for every practicing emergency physician in the country. Every year there are approximately 4.5 million visits to the ED for chest pain and over 1.5 million hospitalizations for acute coronary syndrome (ACS).2 Despite its prevalence, ACS is a difficult diagnosis to evaluate and manage; it involves taking a thorough history and performing a physical as well as performing an electrocardiogram (ECG) and biomarker analysis. The pathogenesis of unstable angina and non-ST segment elevation myocardial infarctions (NSTEMI) involves occlusive narrowing of a coronary artery, usually from an atherosclerotic plaque. The downstream effect of which is inadequate oxygen delivery to the myocardium, resulting in cell death.

Ischemic conditioning is the protective mechanism by which brief episodes of ischemia protect the heart from ischemia-reperfusion injury. There are two types of ischemic conditioning commonly referred to in the literature: pre-conditioning and post-conditioning. In the example of pre-operative coronary artery bypass graft (CABG) patients who may experience a degree of ischemia peri-operatively, ischemic conditioning can be performed before the surgery to prevent or limit myocardial injury. In the example of a patient with an ongoing STEMI who is going to the interventional cardiology suite for a percutaneous intervention, post-ischemic conditioning therapy may prevent or limit myocardial injury. A "remote" qualifier specifies that the therapy is implemented by inducing ischemia at a location that is not the heart itself.

The investigators propose to leverage the novel technique of metabolomics to better study the mechanisms behind ischemic post-conditioning. This study will pair clinical human data with molecular data. It is a novel theoretical concept in the field and the investigators believe that this methodology will be the basis for future research.

The investigators will utilize metabolomics as a tool to gain mechanistic insight into the potential mechanisms of action behind ischemic conditioning. Metabolomics is a burgeoning field of molecular biology that studies the metabolome, the catalogue of material and product of every biochemical reactions in the body occurring at that point in time. As such, the metabolome is ever changing and can reflect what the body is doing, not doing or responding to, and if so, by how much for each of the over 2,500 known human metabolites. Because there is such a large amount of data available by this technique, proper analysis requires the use of proprietary statistical software that can account for the effect of random chance in the data.

The particular innovation to this methodology compared to other studies to date is that we will pair biological as well as clinical data for analysis. This means that even if the investigators cannot find a difference in troponin levels between the treatment and control groups, the investigators will have some data on where to investigate next and be able to detect the biological response that remote post-ischemic conditioning induces. If this particular therapy does not develop any further, at least the investigators will know what appropriate mechanisms are at work and perhaps some of those could be targeted by pharmaceuticals in the future. Finally, if the investigators detect no differences at all, this will serve as an argument against the potential of ischemic post-conditioning in the NSTEMI population.