RESOURCES

BACKGROUND Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality
worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ventricle and delaying
myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective
benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in
LV scar and improves cardiac function remain unknown.

OBJECTIVES This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms,
and determined the late-term impact of primary unloading on myocardial function.

METHODS Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous
left anterior descending artery occlusion.

RESULTS Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion
to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of
genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for
30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived
factor (SDF)-1a, thereby increasing SDF-1a signaling via reperfusion injury salvage kinases, which limits apoptosis within
the infarct zone. Inhibiting SDF-1a activity attenuated the cardioprotective effect of primary unloading. Twenty-eight
days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers
associated with heart failure and maladaptive remodeling.

CONCLUSIONS The authors report for the first time that first mechanically reducing LV work before coronary
reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a
cardioprotective program that includes enhanced SDF-1a activity. Primary unloading further improved LV scar size
and cardiac function 28 days after AMI. (J Am Coll Cardiol 2018;72:501–14) © 2018 Published by Elsevier on behalf of
the American College of Cardiology Foundation.