Original Investigation
Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction

https://doi.org/10.1016/j.jacc.2018.05.034Get rights and content
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Abstract

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)-1α, thereby increasing SDF-1α signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1α 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-1α activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.

Key Words

acute myocardial infarction
cardioprotection
ischemia-reperfusion injury
mechanical circulatory support

Abbreviations and Acronyms

AMI
acute myocardial infarction
BCL-2
B-cell lymphoma-2
BCL-XL
B-cell lymphoma–extra-large
BNP
B-type natriuretic peptide
CMR
cardiac magnetic resonance
DPP
dipeptidyl peptidase
LAD
left anterior descending
LGE
late-gadolinium enhancement
LV
left ventricular
MMP
matrix metalloproteinase
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
P-reperfusion
primary reperfusion
P-unloading
primary unloading
PCR
polymerase chain reaction
SDF
stromal-derived factor
RISK
reperfusion injury salvage kinase
RNA
ribonucleic acid
TV
transvalvular axial-flow

Cited by (0)

This work was supported by a grant from the National Institutes of Health (RO1HL139785-01) to Dr. Kapur and Abiomed Inc. to Tufts Medical Center. Dr. Patel has received reimbursement for consulting services for Patient Management Advisory Council, Abiomed. Dr. Kapur has received institutional grant support and consulting and speaker honoraria from Abiomed Inc., Abbott Inc., Boston Scientific Inc., Medtronic Inc., Maquet/Getinge Inc., and Cardiac Assist. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

Drs. Esposito, Zhang, and Qiao contributed equally to this work and are joint first authors.