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.

Inclusion Criteria:

- Adult patient 18 ≥ years old in the BIDMC ED

- Clinical suspicion of myocardial infarction

- ECG without pathognomonic ST-segment elevation

- At least one positive troponin-T (>0.10)

Exclusion Criteria:

- Inability to consent to enrollment

- Concurrent diagnosis of an emergent condition that may be antecedent to the NSTEMI

- Presentation to the ED greater than 24 hours after onset of NSTEMI symptoms

- Patients with a history of mastectomy or upper extremity arteriovenous fistula.

- Patients with active medication administration in both arms will be excluded from the
study.