A characterization and targeting of the infarct border zone in a swine model of myocardial infarction.
BACKGROUND
Novel therapies for myocardial infarction (MI) involving stem cells, gene therapy, biomaterials, or revascularization strategies have shown promise in animal studies and clinical trials, but results have been limited partially due to the injection of therapeutics into ischemic myocardium that cannot support their mechanism of action. Accurate targeting of therapeutics precisely to the infarct border zone (BZ) may be essential for effective repair of the ischemic heart.


METHODS
Ischemia-reperfusion MI was induced in Yorkshire swine by inflation of an angioplasty balloon in the left anterior descending coronary artery. Fluorescent microspheres were injected into the BZ under NOGA catheter guidance, and this location was identified grossly then examined by immunohistochemistry and Western analysis.


RESULTS
Analysis of the infarct zone two hours post-MI revealed a frankly necrotic region devoid of contractile proteins with marked activation of caspase-3. The NOGA-defined BZ closely approximates the grossly-defined BZ and contains intact myocytes and vasculature. Western analysis detected Akt expression and levels of Ca(2+) handling proteins equivalent to that of viable tissues.


CONCLUSIONS
Histological and Western analysis revealed that NOGA mapping precisely identifies grossly and molecularly defined infarct BZ at a location where there are still viable cells and vessels capable of supporting novel therapeutic strategies.
Temple University School of Medicine, Cardiovascular Research Center, Temple University, PA, USA.
Jason M
JM
Duran
Sharven
S
Taghavi
Remus M
RM
Berretta
Catherine A
CA
Makarewich
Thomas
T
Sharp Iii
Tim
T
Starosta
Foram
F
Udeshi
Jon C
JC
George
Hajime
H
Kubo
Steven R
SR
Houser
D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D005455:Fluorescent Antibody Technique; D006334:Heart Function Tests; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010768:Phosphoserine / Q000378:metabolism; D034421:Sus scrofa
D010768:Phosphoserine