Measurement of Matrix Metalloproteinase Activation Post Myocardial Infarction

Patients who are admitted to Yale New Haven Hospital with first acute myocardial infarction
within the onset of 12 hours of symptoms will be eligible for this study and referred by
their physician for this study. Subjects will be screened with medical interview and
physical exam for eligibility. Clinical data will be obtained for demographic purposes
including: EKG upon admission, serum cardiac markers, basic metabolic panel, cardiac
catheterization report and recent echocardiography report. All standard medications will be
allowed which include diuretics, ACE/Ang-II inhibitors, nitrates/hydralazine, digoxin, low
dose aspirin, beta-blockers, calcium channel antagonists, anticoagulants and anti-arrhythmic
agents.

A 10cc blood sample will be drawn from a peripheral vein at 3 days post myocardial
infarction into chilled EDTA tubes, plasma decanted and placed at -70 degrees C until
MMP/TIMP assays are performed. These samples will be sent to collaborators at the Medical
University of South Carolina for high sensitivity plasma assays developed at MUSC for MMP-1,
-13, -8, -2, -9 and TIMP-1, -2, -4. [1] These assays will be performed in Core C and
detailed description of specificity of these measurements is described. In addition, indices
of collagen synthesis and degradation, through the use of telopeptide measurements will be
measured in these plasma samples.

Nitroglycerin resting Tl-201 myocardial perfusion imaging will be performed between 2-5 days
after myocardial infarction. Subjects will have a peripheral intravenous line placed and
will be injected with 2.5-3.5mCi of Tl-201. The Tl-201 given will be a slightly lower dosage
than the standard clinical protocol of Yale New Haven Hospital nuclear cardiology lab
because of improved reconstruction algorithms with CT will allow lower doses of radioactive
isotopes. Resting myocardial perfusion images will be acquired 5 minutes post-injection on a
multislice helical SPECT/CT (GE Infinia Hawkeye) followed by a CT scan. A redistribution
image will be performed 4 hours after thallium administration. Each SPECT scan will take
approximately 25 minutes. Perfusion defect size will be quantified using the Yale C-Q method
previously described [2].

Transthoracic echocardiography will be performed at 2-5 days post-MI and 28 days after MI in
standard apical and parasternal views using a commercial ultrasound system either Phillips
7500 or IE33 ultrasound imaging system with an S3 transducer. The transducer will be placed
on the apical and/or parasternal location on the chest and ECG-gated images will be obtained
during a breath hold. Each acquisition will be performed in zoom mode at 40 Hz, over the
entire LV in 4 cardiac cycles with 40 frames per cardiac cycle. Image data will be captured
in digital form and will be backed up on DVDs. NOTE: No patient HIPPA data will be saved on
the DVD. Left ventricular ejection fraction (LVEF), end-diastolic volume (LVEDV), and
end-systolic volume (LVESV) will be measured. The echocardiograms will be used to determine
LV mass, LV cavity size and regional thickening. Patients will undergo MRI with gadolinium
contrast in the GE Signa 1.5 tesla magnetic resonance image scanner located in the Yale-New
Haven Hospital MRI Center, using standard ECG-gated cine gradient echo, and echo-planar,
phase contrast and MR tagged imaging sequences.

Electrocardiographic monitoring will be maintained during the magnetic resonance imaging.
MRI scans will occur between 2-5 days post-MI.

The first acquisitions to be performed will be combined cine-gradient echo/cine phase
velocity approach that will obtain both the magnitude images required for our segmentation
and shape-based tracking as well as contrast data for finding midwall myocardial velocities
in a single image acquisition. This sequence will yield adjacent 5 mm thick axial images
with in plane resolution of approximately 1.6mm x 1.6mm. We will acquire 16-20 cardiac phase
per location. Patients will receive 0.1 mmol/kg of standard gadolinium contrast in a
peripheral IV. The acquisition will apply inversion recovery preparatory pulse to null
normal myocardium, followed by a segmented k-space gradient echo acquisition. We anticipate
that all of the proposed magnetic resonance imaging for each subject will be completed
within 2 hours. The technologist or doctor operating the scanner will be able to see the
subject. The operator will maintain contact by voice with the subjects.

None of the aforementioned procedures are considered experimental and individually, may or
may not be part of the subjects' standard of care post myocardial infarction. During each
part of the step of image acquisition, there will be a physician present. All data will be
transferred via network to the image processing laboratory for analysis and will not include
any projected personal information.

Inclusion Criteria:

- Diagnosis of acute myocardial infarction characterized by (1) greater than 30 minutes
of chest pain; (2) ST elevation in 2 contiguous leads greater than 2mV; and (3)
elevated serum markers greater than three times the normal value.

- Males or females 18 years of age or older.

- Adequate intravenous access in one arm.

- Willing to comply with the requirements of the protocol.

- Provided written informed consent to participate in the study.

Exclusion Criteria:

- History of significant co-morbidity requiring hospitalization separate from acute
myocardial infarction (i.e. metastatic cancer).

- History of/current structural heart disease.

- Arrhythmia

- History of previous myocardial infarction

- History of coronary revascularization

- Cardiogenic shock

- Hypotension

- Renal failure (creatinine >2mg/dl) or hyperkalemia (serum potassium > 5.5mg/dl)

- History of allergic reaction to gadolinium

- Contraindication to undergo MR imaging (pacemaker, metallic implants, etc)

- History of claustrophobia

- Pregnant or breast-feeding, or (if pre-menopausal), not practicing acceptable method
of birth control.

- History of any other conditions, which in the judgment of the investigator, are
likely to hinder or confuse study conduct or to pose a safety concern to the patient.

- Resting HR >110

- Chronic tetracycline or doxycycline use

- Ongoing/active rheumatic disease requiring significant anti-inflammatory agents,
steroids or immunosuppression

- Not capable of informed consent